Treatment for peritoneal dialysis-associated peritonitis

  • Conclusions changed
  • Review
  • Intervention

Authors

  • Angela E Ballinger,

    1. University of Otago Christchurch, Department of Medicine, Christchurch, New Zealand
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  • Suetonia C Palmer,

    1. University of Otago Christchurch, Department of Medicine, Christchurch, New Zealand
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  • Kathryn J Wiggins,

    Corresponding author
    1. Royal Melbourne Hospital, Departments of Nephrology and General Medicine, Melbourne, VIC, Australia
    • Kathryn J Wiggins, Departments of Nephrology and General Medicine, Royal Melbourne Hospital, Melbourne, VIC, Australia. kate.wiggins@mh.org.au.

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  • Jonathan C Craig,

    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia
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  • David W Johnson,

    1. Princess Alexandra Hospital, Department of Nephrology, Woolloongabba, Queensland, Australia
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  • Nicholas B Cross,

    1. Christchurch Public Hospital, Department of Nephrology, Christchurch, New Zealand
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  • Giovanni FM Strippoli

    1. The University of Sydney, Sydney School of Public Health, Sydney, NSW, Australia
    2. The Children's Hospital at Westmead, Cochrane Renal Group, Centre for Kidney Research, Westmead, NSW, Australia
    3. University of Bari, Department of Emergency and Organ Transplantation, Bari, Italy
    4. Mario Negri Sud Consortium, Department of Clinical Pharmacology and Epidemiology, Santa Maria Imbaro, Italy
    5. Diaverum, Medical-Scientific Office, Lund, Sweden
    6. Amedeo Avogadro University of Eastern Piedmont, Division of Nephrology and Transplantation, Department of Translational Medicine, Novara, Italy
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Abstract

Background

Peritonitis is a common complication of peritoneal dialysis (PD) that is associated with significant morbidity including death, hospitalisation, and need to change from PD to haemodialysis. Treatment is aimed to reduce morbidity and recurrence. This is an update of a review first published in 2008.

Objectives

To evaluate the benefits and harms of treatments for PD-associated peritonitis.

Search methods

For this review update we searched the Cochrane Renal Group's Specialised Register to March 2014 through contact with the Trials Search Co-ordinator using search terms relevant to this review. Studies contained in the Specialised Register are identified through search strategies specifically designed for CENTRAL, MEDLINE and EMBASE, and handsearching conference proceedings.

Selection criteria

We included randomised controlled trials (RCTs) and quasi-RCTs assessing the treatment of peritonitis in PD patients (adults and children). We included any study that evaluated: administration of an antibiotic by different routes (e.g. oral, intraperitoneal (IP), intravenous (IV)); dose of an antibiotic agent; different schedules of administration of antimicrobial agents; comparisons of different regimens of antimicrobial agents; any other intervention including fibrinolytic agents, peritoneal lavage and early catheter removal.

Data collection and analysis

Multiple authors independently extracted data on study risk of bias and outcomes. Statistical analyses were performed using the random effects model. We expressed summarised treatment estimates as a risk ratio (RR) with 95% confidence intervals (CI) for dichotomous outcomes and mean difference (MD) with 95% CI for continuous outcomes.

Main results

We identified 42 eligible studies in 2433 participants: antimicrobial agents (36 studies); urokinase (4 studies), peritoneal lavage (1 study), and IP immunoglobulin (1 study). We did not identify any optimal antibiotic agent or combination of agents. IP glycopeptides (vancomycin or teicoplanin) had uncertain effects on primary treatment response, relapse rates, and need for catheter removal compared to first generation cephalosporins, although glycopeptide regimens were more likely to achieve a complete cure (3 studies, 370 episodes: RR 1.66, 95% CI 1.01 to 2.72). For relapsing or persistent peritonitis, simultaneous catheter removal and replacement was better than urokinase at reducing treatment failure rates (RR 2.35, 95% CI 1.13 to 4.91) although evidence was limited to a single small study. Continuous and intermittent IP antibiotic dosing schedules had similar treatment failure and relapse rates. IP antibiotics were superior to IV antibiotics in reducing treatment failure in one small study (RR 3.52, 95% CI 1.26 to 9.81). Longer duration treatment (21 days of IV vancomycin and IP gentamicin) had uncertain effects on risk of treatment relapse compared with 10 days treatment (1 study, 49 patients: RR 1.56, 95% CI 0.60 to 3.95) although may have increased ototoxicity.

In general, review conclusions were based on a small number of studies with few events in which risk of bias was generally high; interventions were heterogeneous, and outcome definitions were often inconsistent. There were no RCTs evaluating optimal timing of catheter removal and data for automated PD were absent.

Authors' conclusions

Many of the studies evaluating treatment of PD-related peritonitis are small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. IP administration of antibiotics was superior to IV administration for treating PD-associated peritonitis and glycopeptides appear optimal for complete cure of peritonitis, although evidence for this finding was assessed as low quality. PD catheter removal may be the best treatment for relapsing or persistent peritonitis.

Evidence was insufficient to identify the optimal agent, route or duration of antibiotics to treat peritonitis. No specific antibiotic appears to have superior efficacy for preventing treatment failure or relapse of peritonitis, but evidence is limited to few trials. The role of routine peritoneal lavage or urokinase is uncertain.

Plain language summary

What is the best treatment to manage peritonitis in people on peritoneal dialysis?

People with advanced kidney disease can be treated with peritoneal dialysis (PD) which involves a catheter being permanently inserted into the lining around the abdominal organs (the peritoneum) through the abdominal wall. Sterile fluid is drained in and out several times each day. The peritoneal lining enables movement of salts and toxins that accumulate when kidney function cannot maintain usual function. Wastes from the bloodstream are moved into the dialysis fluid and removed with the fluid as it is drained from the body.

The most common serious complication of PD is infection of the peritoneal lining - peritonitis. Effective treatment is necessary to reduce risk of recurrent infection, needing to stop PD, poor peritoneal membrane function, and potentially prolonged hospital admission or death.

This review of interventions for PD-associated peritonitis identified 42 studies (2433 participants). Many studies were small, out-dated, of poor quality, and had inconsistent definitions and dosing regimens. In general, information about the best treatment of peritonitis in people on PD may be insufficient to guide therapy.

We found that intraperitoneal antibiotics appear to improve treatment responses compared with IV antibiotics. Glycopeptides may increase likelihood of cure compared with first generation cephalosporins. There appears to be no certain role for routine peritoneal lavage (washing) or use of clot-breaking (fibrinolytic) agents.

New and larger randomised controlled trials that compare the effects of IV versus intraperitoneal antibiotics and different antibiotic types on patient-relevant outcomes including adequate assessment of treatment harms are still needed.

Background

Description of the condition

Peritoneal dialysis (PD) is an effective form of renal replacement therapy for people with advanced kidney disease. However, peritonitis continues to represent a significant complication of PD (Voinescu 2002) despite the introduction of effective prevention strategies such as disconnect and double bag systems (Bazzato 1980; Monteon 1998; Strippoli 2004). The reported incidence of peritonitis episodes varies from one in nine patient-months to one in 53 patient-months (Grunberg 2005; Kawaguchi 1999). Risk factors for peritonitis include diabetes mellitus (Oxton 1994), race (Juergensen 2002; Lim 2005), obesity (McDonald 2004), temperate climates (Alves 1993; Szeto 2003), and depression (Troidle 2003). In addition, some studies have shown that PD modality may influence peritonitis rates, although other studies have not confirmed this (Huang 2001; Oo 2005).

PD-associated peritonitis results in significant morbidity, and in some cases, mortality. Catheter removal becomes necessary in cases not responding to antibiotic therapy. This may be temporary and followed by a return to PD, or permanent, resulting in technique failure. Ultrafiltration failure can occur both acutely due to increases in capillary permeability (Ates 2000; Smit 2004) and in the longer term result in technique failure (Coles 2000; Davies 1996). In many countries, peritonitis is a leading cause of permanent transfer to haemodialysis. Peritonitis is prevalent among patients with encapsulating sclerosing peritonitis and may be a causal factor (Kawanishi 2005; Rigby 1998). In some patient groups peritonitis is thought to increase overall mortality rates (Fried 1996). It is estimated that PD-associated peritonitis results in death in 6% of affected patients (Troidle 2006).

Description of the intervention

Early and effective management of peritonitis is important to reduce the risk of adverse outcomes such as catheter removal (Choi 2004; Heaf 2004). The mainstay of treatment is antimicrobial therapy, although adjunctive therapies have been employed including the use of fibrinolytic agents (Innes 1994; Pickering 1989), peritoneal lavage (Ejlersen 1991) and routine early catheter removal.

How the intervention might work

Current guidelines recommend the use of antibiotics which cover gram positive and gram negative organisms in cases of peritonitis (CARI 2005; Piraino 2005). However, several questions about the optimal treatment of PD-associated peritonitis remain unanswered, particularly with respect to choice, route of administration (Passadakis 2001) and duration of antimicrobial therapy. Many treatment regimens are based on continuous ambulatory PD (CAPD) and their applicability to automated PD (APD) is untested (Fielding 2002). The optimal total duration of antimicrobial therapy, and the duration of systemic (intraperitoneal (IP) or intravenous (IV)) treatment is also unclear, as are the roles of peritoneal lavage and urokinase. The majority of studies performed have focused on the outcomes of empirical antibiotic therapy, with little consideration of treatment initiated once organism identification and sensitivities are available.

Why it is important to do this review

To address existing uncertainties, we performed a systematic review of randomised controlled trials (RCT) evidence examining the effectiveness of different treatment options for PD-associated peritonitis.

Objectives

To evaluate the benefits and harms of treatments for PD-associated peritonitis.

Methods

Criteria for considering studies for this review

Types of studies

All RCTs and quasi-RCTs (RCTs in which allocation to treatment was obtained by alternation, use of alternate medical records, date of birth or other predictable methods) on the effect of any interventions, including anti-infective agents, fibrinolytic agents, peritoneal lavage and early catheter removal, for the treatment of peritonitis in PD patients were included.

Types of participants

Adult and paediatric patients who were receiving PD (CAPD or APD) and developed PD-associated peritonitis.

Types of interventions

Studies looking at the use of any antimicrobial agent, fibrinolytic agent, peritoneal lavage, IP immunoglobulin or early catheter removal were included. Interventions could be tested directly against each other or compared to placebo/no treatment. The following could be included:

  • Studies of the same antibiotic agent administered by different routes (e.g. IP versus oral, IP versus IV).

  • Studies comparing the same antibiotic agent administered at different doses.

  • Studies comparing different schedules of administration of antimicrobial agents (in particular regimens involving single daily dosing versus more than one daily dose).

  • Comparisons of different regimens of antimicrobial agents.

  • Studies comparing different treatment durations with the same antimicrobial agents.

  • Studies comparing any other intervention including fibrinolytic agents, peritoneal lavage, IP immunoglobulin administration, and early catheter removal.

Types of outcome measures

Primary outcomes
  1. Primary peritonitis treatment failure (failure to achieve a clinical response, defined as resolution of symptoms and signs, by day 4 to 6)

  2. Complete cure (clinical or microbiological improvement or both with no subsequent relapse)

  3. Peritonitis relapse (reoccurrence of peritonitis due to the same organism with the same antibiotic sensitivities within 28 days of completing treatment)

  4. Death due to peritonitis (all-cause mortality data were also collected)

  5. Toxicity of antibiotic treatments (ototoxicity, decline in residual kidney function, rash, nausea and vomiting, convulsions, other).

Secondary outcomes
  1. Time to peritonitis relapse

  2. Need to change antibiotic following culture results

  3. Catheter removal or replacement or both

  4. Hospitalisation (duration of hospital stay) and hospitalisation rate (number of patients hospitalised)

  5. Technique failure (transfer from PD to haemodialysis or transplantation due to peritonitis).

Search methods for identification of studies

Electronic searches

For this update we searched the Cochrane Renal Group's Specialised Register and EMBASE to 5 March 2014 without language restriction.

The Cochrane Renal Group’s Specialised Register contains studies identified from:

  1. Monthly searches of the Cochrane Central Register of Controlled Trials (CENTRAL)

  2. Weekly searches of MEDLINE OVID SP

  3. Handsearching of renal-related journals and the proceedings of major renal conferences

  4. Searching of the current year of EMBASE OVID SP

  5. Weekly current awareness alerts for selected renal journals

  6. Searches of the International Clinical Trials Register (ICTRP) Search Portal and ClinicalTrials.gov.

Studies contained in the Specialised Register are identified through search strategies for CENTRAL, MEDLINE, and EMBASE based on the scope of the Cochrane Renal Group. Details of these strategies, as well as a list of handsearched journals, conference proceedings and current awareness alerts, are available in the Specialised Register section of information about the Cochrane Renal Group.

Please refer to our review published in 2008 for the original search strategies used (Wiggins 2008).

Searching other resources

  1. Reference lists of clinical practice guidelines, review articles and relevant studies.

  2. Letters seeking information about unpublished or incomplete studies to investigators known to be involved in previous studies.

Data collection and analysis

Selection of studies

The original review was undertaken by four authors in 2008 and seven authors in 2014. The search strategies described were used to obtain titles and abstracts of studies that might be relevant to the review. The titles and abstracts were screened independently by multiple authors, who discarded studies that were not eligible based on the inclusion criteria for this review; however studies and reviews that might include relevant data or information on additional published or unpublished studies were retained initially and their full-text version was analysed.

Data extraction and management

Four authors independently assessed the retrieved abstracts, and if necessary, the full text of these studies to determine eligibility. Data extraction was carried out independently by the same authors using standard data extraction forms. Studies reported in non-English language journals were translated before assessment. Where more than one publication of one study existed, reports were grouped together and the publication with the most complete data was used in the analyses. Where relevant outcomes were only published in earlier versions these data were used Disagreements were resolved in consultation among authors.

Assessment of risk of bias in included studies

The following items were independently assessed by two authors using the risk of bias assessment tool (Higgins 2011) (see Appendix 2).

  • Was there adequate sequence generation (selection bias)?

  • Was allocation adequately concealed (selection bias)?

  • Was knowledge of the allocated interventions adequately prevented during the study (detection bias)?

    • Participants and personnel

    • Outcome assessors

  • Were incomplete outcome data adequately addressed (attrition bias)?

  • Are reports of the study free of suggestion of selective outcome reporting (reporting bias)?

  • Was the study apparently free of other problems that could put it at a risk of bias?

Measures of treatment effect

Results were expressed as risk ratio (RR) with 95% confidence intervals (CI) for all categorical outcomes of the individual studies.

Dealing with missing data

Any further information or clarification required from the authors was requested by written or electronic correspondence and relevant information obtained in this manner was included in the review. Evaluation of important numerical data such as screened, randomised patients as well as intention-to-treat (ITT), as-treated and per-protocol (PP) population was performed. Attrition rates, for example drop-outs, losses to follow-up and withdrawals were investigated. Issues of missing data and imputation methods (for example, last-observation-carried-forward (LOCF)) were critically appraised (Higgins 2011).

Assessment of heterogeneity

Heterogeneity was analysed using a Chi² test on N-1 degrees of freedom, with an alpha of 0.05 used for statistical significance and with the I² statistic (Higgins 2003). I² values of 25%, 50% and 75% correspond to low, medium and high levels of heterogeneity.

Assessment of reporting biases

It was planned that if sufficient RCTs were identified an attempt would be made to assess funnel plot asymmetry due to small study effect, as this may be indicative of publication bias (Egger 1997). There were however too few included studies to construct meaningful funnel plots.

Data synthesis

Treatment effects were summarised using a random-effects model. For each analysis, the fixed-effect model was also evaluated to ensure robustness of the model chosen and susceptibility to outliers. Where continuous scales of measurement were used to assess the effects of treatment (time to peritonitis relapse, days of hospitalisation, measures of residual kidney function) the mean difference (MD) was used.

Subgroup analysis and investigation of heterogeneity

Subgroup analysis was planned to explore how possible sources of heterogeneity (paediatric versus adult population, age, gender, cause of end-stage kidney disease, body mass index, diabetes mellitus, duration of dialysis, PD modality (CAPD versus APD), previous peritonitis episodes, type of dialysate and micro-organism isolated) might influence treatment effect.

Sensitivity analysis

We aimed to perform sensitivity analyses to explore the influence of the following factors on effect size:

  • repeating the analysis excluding unpublished studies

  • repeating the analysis taking account of risk of bias

  • repeating the analysis excluding any very long or large studies to establish how much they dominate the results

  • repeating the analysis excluding studies using the following filters: diagnostic criteria, language of publication, source of funding (industry versus other), country.

Data were however insufficient to perform these analyses.

Results

Description of studies

Results of the search

The literature search undertaken for Wiggins 2008 retrieved 1684 reports of which 1617 were excluded. Analysis of the remainder identified 36 studies (2089 participants, 2480 peritonitis episodes) published in 42 reports. For this update the Cochrane Renal Group's Specialised Register identified 62 reports of potential studies and two ongoing studies. After full text review a further six eligible studies (344 participants, 533 peritonitis episodes) were identified taking the total number of unique RCTs to 42 (58 reports; 2433 participants, 3013 episodes of peritonitis). Search results are summarised in Figure 1.

Figure 1.

Study flow diagram.

Included studies

We identified 36 studies (1949 patients) that considered the use of antimicrobial agents. There were 14 studies that compared different routes of antibiotic administration - IP versus IV (3 studies, 156 participants: Bailie 1987; Bennett-Jones 1987; Vargemezis 1989) and IP versus oral (11 studies, 601 participants: Bennett-Jones 1990; Boeschoten 1985; Chan 1990; Cheng 1991; Cheng 1993; Cheng 1997; Cheng 1998; Gucek 1994; Lye 1993; Raman 1985; Tapson 1990).

Different IP antibiotic classes or combinations or both were tested head-to-head in 17 studies (Bowley 1988; de Fijter 2001; Drinovec 1988; Flanigan 1991; Friedland 1990; Gucek 1997; Hernandez 2004 Jiménez 1996; Khairullah 2002; Klaus 1995a; Leung 2004; Lui 2005; Lupo 1997; Merchant 1992; Wale 1992; Were 1992; Wong 2001). These included three studies (234 participants) that compared glycopeptides to first generation cephalosporins (Flanigan 1991; Khairullah 2002; Lupo 1997); and five studies (421 participants) that compared intermittent and continuous IP antibiotic dosing (Boyce 1988; Choy 2001; Lye 1995; Klaus 1995a; Velasquez-Jones 1995).

There were six studies that investigated adjunctive therapies: urokinase versus placebo (Gadallah 2000c; Innes 1994; Tong 2005a); catheter removal or replacement or both (Williams 1989), peritoneal lavage (Ejlersen 1991), and IP immunoglobulin (Coban 2004). Data for automated PD were absent.

Excluded studies

We excluded 49 studies (67 reports). Reasons for exclusion were: not RCTs (19); not appropriate population (24); not peritonitis treatment (2); not appropriate outcomes (4).

Risk of bias in included studies

We have summarised the risk of bias of included studies in Figure 2 and Figure 3. In general, risks of bias were in high in most studies. Overall, both blinding and selective reporting were assessed at high risk of bias. Suboptimal reporting in many studies meant that risks of bias were assessed as unknown.

Figure 2.

Risk of bias graph: review authors' judgements about each risk of bias item presented as percentages across all included studies

Figure 3.

Risk of bias summary: review authors' judgements about each risk of bias item for each included study

Allocation

Random generation sequence was assessed as low risk in four studies (10%) (Chan 1990; Cheng 1991; Lui 2005; Tapson 1990); allocation concealment was adequate in 7/42 (17%) studies (Cheng 1991; Cheng 1998; Friedland 1990; Klaus 1995a; Lui 2005; Tapson 1990; Wong 2001).

Blinding

Only three (7%) studies clearly blinded participants and investigators (Cheng 1991; Innes 1994; Tong 2005a).

Incomplete outcome data

Percentages of participants lost to follow-up ranged from 0% to 64.5%.

Selective reporting

Reporting of outcomes was assessed as low risk in only six (14%) studies (de Fijter 2001; Friedland 1990; Lye 1993; Merchant 1992; Tong 2005a; Wong 2001).

Effects of interventions

There were no significant differences in the results of analyses performed using random and fixed-effects models. The results presented therefore refer to those obtained using a random-effects model. Subgroup analyses and evaluations for bias from small-study effects were not performed because the small numbers of participants and studies made the power of these analyses too small to assess. Few data were available on the pharmacokinetics of many commonly used antibiotics when administered intraperitoneally.

Intravenous (IV) versus intraperitoneal (IP) antimicrobial agents

Bennett-Jones 1987 reported a statistically significant increase in the primary treatment failure rate for IV versus IP vancomycin and tobramycin (Analysis 1.1.2 (75 participants): RR 3.52, 95% CI 1.26 to 9.81). It is noteworthy that in the study by Bailie 1987, in which IP versus IV administration of a loading dose of vancomycin followed by an IP maintenance dose were compared, there were no primary treatment failures reported in either group. Vargemezis 1989 also looked at IP versus IV administration of vancomycin; however, reporting limitations made it difficult to interpret meaningful results.

Bailie 1987 reported no significant differences in the incidence of rash (Analysis 1.2.1 (20 participants): RR 5.00, 95% CI 0.27 to 92.62) or infusion pain (Analysis 1.3 (20 participants): RR 3.00, 95% CI 0.14 to 65.90) between IV and IP vancomycin. Bennett-Jones 1987 reported no significant difference in hypotension (Analysis 1.2.2 (76 participants): RR 5.26, 95% CI 0.26 to 106.11) between IV and IP vancomycin and tobramycin.

Oral versus IP administration of the same antimicrobial agent

Oral administration of quinolone antibiotics (ciprofloxacin, ofloxacin) had uncertain effects on primary treatment failure compared to IP administration (Analysis 2.1 (2 studies, 83 participants): RR 1.34, 95% CI 0.71 to 2.56; P = 0.37; I²= 0%) and relapse (Analysis 2.2 (2 studies, 83 participants): RR 3.38, 95% CI 0.74 to 15.35; P = 0.11; I² = 0%). Assessment of low-quality evidence indicated that IP quinolone therapy may increase complete cure (Analysis 2.3 (2 studies, 83 participants): RR 1.66, 95% CI 0.98 to 2.83; P = 0.06; I² = 0%) compared with oral treatment, although therapy failure rates were high in both arms of these studies (52.4% and 31.7% in the oral and IP groups, respectively).

Cheng 1993 reported no significant differences in catheter removal rates (Analysis 2.4 (48 participants): RR 2.00, 95% CI 0.19 to 20.61), hospitalisation rates (Analysis 2.5 (48 participants): RR 1.00, 95% CI 0.51 to 1.95), or nausea and vomiting (Analysis 2.6 (48 participants): RR 0.50, 95% CI 0.05 to 5.15) between oral and IP cephalosporin (cephradine) therapy.

Oral versus IP administration of different antimicrobial agents

Comparison of oral versus antibiotic regimens had uncertain effects on risks of failure to achieve complete cure (Analysis 3.1 (8 studies, 510 participants): RR 1.06, 95% CI 0.80 to 1.40; P = 0.69; I² = 0%). Subgroup analysis showed this was similar for oral quinolones versus IP aminoglycoside/glycopeptide combinations (Analysis 3.1.1 (5 studies, 304 participants): RR 1.19, 95% CI 0.83 to 1.72), oral quinolones versus IP cephalosporins (Analysis 3.1.2 (2 studies, 148 participants): RR 1.00, 95% CI 0.55 to 1.81), and oral cephradine versus IP cefuroxime (Analysis 3.1.3 (58 participants): RR 0.77, 95% CI 0.40 to 1.46). Similarly, primary treatment failure (Analysis 3.2 (7 studies, 472 participants): RR 1.04, 95% CI 0.64 to 2.15; P = 0.86; I² = 0%), relapse (Analysis 3.3 (5 studies, 304 participants): RR 1.17, 95% CI 0.64 to 2.15; P = 0.61; I² = 2%), catheter removal (Analysis 3.4 (2 studies, 170 participants): RR 1.18, 95% CI 0.49 to 2.87; P = 0.71; I² = 0%), hospitalisation rate (Analysis 3.5 (1 study, 45 participants): RR 0.70, 95% CI 0.30 to 1.63), all-cause mortality (Analysis 3.6 (1 study, 46 participants): RR 0.36, 95% CI 0.02 to 8.46), and microbiological eradication (not defined by investigators) (Analysis 3.7 (1 study, 39 participants): RR 1.26, 95% CI 0.46 to 3.46) were equivalent in both groups. There was an increased risk of nausea and vomiting with oral antibiotics compared to IP antibiotics (Analysis 3.8.1 (3 studies, 158 participants): RR 9.91, 95% CI 1.89 to 51.99; P = 0.007; I² = 0%).

Oral versus IP administration of the same or different antimicrobial agent(s)

When all studies that compared oral versus IP administration of an antimicrobial agent were combined, treatment failure rates of oral versus IP administration were similar without evidence for between-trial heterogeneity (Analysis 4.1 (9 studies, 555 participants): RR 1.12, 95% CI 0.79 to 1.60; P = 0.52; I² = 0%).

Low versus high dose antibiotic

Merchant 1992 reported low dose imipenem (total 1 g IP daily) was associated with a significant increase in failure to achieve complete cure (Analysis 5.1 (30 participants): RR 4.38, 95% CI 1.27 to 15.06) and the number relapsing (Analysis 5.2 (28 participants): RR 12.00, 95% CI 1.60 to 90.23) compared with high dose imipenem (total 2 g IP daily). High dose imipenem had an uncertain effect on seizures (Analysis 5.3 (30 participants): RR 0.60, 95% CI 0.03 to 11.23). However this study was not powered to detect seizures and the protocol was changed mid-study from high dose to low dose imipenem because two participants in the imipenem group had seizures.

Intermittent versus continuous IP antimicrobial agents

The effects of intermittent compared with continuous dosing on complete cure (Analysis 6.1 (4 studies, 338 participants): RR 0.92, 95% CI 0.64 to 1.33; P = 0.65; I² = 0%), primary treatment failure (Analysis 6.2 (5 studies, 522 participants): RR 1.11, 95% CI 0.77 to 1.62; P = 0.57; I² = 0%) and risk of relapse (Analysis 6.3 (4 studies, 338 participants): RR 0.76, 95% CI 0.45 to 1.28; P = 0.31; I² = 0%) were uncertain. Choy 2001 reported no significant difference in catheter removal rates between groups (Analysis 6.4 (20 participants): 0.98, 95% CI 0.43 to 2.24). The only side-effect evaluated was vancomycin-induced rash (Boyce 1988); effects of continuous compared with intermittent dosing were uncertain (Analysis 6.5 (51 participants): RR 0.70, 95% CI 0.05 to 10.57).

First generation cephalosporin versus glycopeptide-based regimens

Achievement of complete cure was significantly more likely with a glycopeptide-based regimen than one based on cephalosporins (Analysis 7.1 (3 studies, 370 participants): RR 1.66, 95% CI 1.01 to 2.72; P = 0.04; I² = 41%). This was true for both vancomycin (Analysis 7.1.1 (2 studies, 305 participants): RR 1.51, 95% CI 1.03 to 2.22; P = 0.26; I² = 20%) and teicoplanin-based regimens (Analysis 7.1.2 (1 study, 65 participants): RR 9.65, 95% CI 1.04 to 20.58). Despite the overall advantage of glycopeptides on complete cure, effects on primary treatment failure (Analysis 6.2 (2 studies, 305 participants): RR 1.14, 95% CI 0.69 to 1.87; P = 0.38; I² = 0%), relapse (Analysis 7.3 (3 studies, 350 participants): RR 1.68, 95% CI 0.84 to 3.36; P = 0.14; I² = 0%), catheter removal (Analysis 7.4 (2 studies, 305 participants): RR 0.95, 95% CI 0.41 to 2.19; P = 0.90; I² = 52%) and microbiological eradication (Analysis 7.5 (1 study, 45 participants): RR 0.83, 95% CI 0.62 to 1.13) were uncertain likely due to the lack of power within the meta-analysis.

It is noteworthy that these results were largely influenced by Flanigan 1991 in which the cephazolin dose used was 50 mg/L, which is below the dose currently recommended in the International Society for Peritoneal Dialysis (ISPD) guidelines of 125 mg/L (Li 2010). In contrast, Khairullah 2002 found no difference in cure rates for vancomycin and cephazolin (50% and 40% complete cure for glycopeptides and cephalosporins respectively) when a higher cephalosporin dose was used.

Teicoplanin versus vancomycin-based IP antibiotic regimens

Primary treatment failure was less likely with teicoplanin than vancomycin (Analysis 8.1 (2 studies, 178 participants): RR 0.36, 95% CI 0.13 to 0.96; P = 0.04), however, effects on complete cure were uncertain (Analysis 8.2 (2 studies, 178 participants): RR 0.67, 95% CI 0.40 to 1.15; P = 0.14; I² = 0%). The risk of relapse rates was also similar for both agents (Analysis 8.3 (2 studies, 178 participants): RR 1.01, 95% CI 0.49 to 2.11; P = 0.97; I² = 0%). There was no significant heterogeneity associated with either outcome.

Different regimens of oral antibiotics

Effects of oral rifampicin and ofloxacin (regimen 2) compared with oral ofloxacin alone (regimen 1) (Chan 1990) in achieving a complete cure (Analysis 9.1 (74 participants): RR 0.88, 95% CI 0.35 to 2.17) and catheter removal (Analysis 9.2 (74 participants): RR 2.00, 95% CI 0.19 to 21.11) were uncertain. Chan 1990 also reported there was no differences in the need to change antibiotics following culture results (Analysis 9.3 (74 participants): RR 0.33, 95% CI 0.04 to 3.06), nausea and vomiting (Analysis 9.4.1 (74 participants): RR 3.00, 95% CI 0.13 to 71.34) and rash (Analysis 9.4.2 (74 participants): RR 3.00, 95% CI 0.13 to 71.34) between the two regimens.

Fibrinolytic agents versus non-urokinase or placebo

Studies of IP urokinase found uncertain effects for benefit of urokinase versus placebo on complete cure in persistent peritonitis (Analysis 10.1 (88 participants): RR 1.23, 95% CI 0.84 to 1.79), or primary response to treatment in the setting of resistant peritonitis (Analysis 10.2 (2 studies, 99 participants): RR 0.63, 95% CI 0.32 to 1.26; P = 0.19; I² = 33%). Resistant CAPD peritonitis was defined as either persistent infection or recurrent infection (Innes 1994) or as persistence of symptoms and signs of peritonitis together with turbid peritoneal dialysate 48 hours after the initiation of antibiotic treatment (Tong 2005a). Persistent infection was defined as no resolution of peritonitis within four days of treatment with antibiotics active against the bacteria isolated (Innes 1994). Relapse and catheter removal were uncertain with urokinase, either in the setting of persistent peritonitis (Analysis 10.3.1; Analysis 10.4.1) or initiation of fibrinolytic therapy at the time peritonitis was diagnosed (Analysis 10.3.2; Analysis 10.4.2). Tong 2005a reported no significant difference in all-cause mortality (Analysis 10.5).

Urokinase versus simultaneous catheter removal and replacement

In Williams 1989, a study of participants presenting with a second recurrence of peritonitis, simultaneous catheter removal and replacement was better than urokinase in reducing recurrent episodes of peritonitis (Analysis 11.1 (37 participants): RR 2.35, 95% CI 1.13 to 4.91).

Peritoneal lavage

Ejlersen 1991 investigated the effects of peritoneal lavage (2 L exchanges during the initial 24 hours, no dwell time with dialysis fluid (60 L) containing vancomycin 20 mg/L and netilmicin) plus nine further days antibiotic treatment compared with continued prolonged exchanges (2 rapid exchanges containing vancomycin (40 mg/L) followed by routine CAPD schedule including antibiotics for 10 days. This study reported no significant differences between lavage and usual care for complete cure (Analysis 12.1 (36 participants): RR 2.50, 95% CI 0.56 to 11.25), relapse of peritonitis with subsequent laparotomy and colostomy (Analysis 12.2 (36 participants): RR 2.50, 95% CI 0.56 to 11.25), technical failure (Analysis 12.3 (36 participants): RR 3.00, 95% CI 0.13 to 69.09), or adverse events (Analysis 12.4 (36 participants): 3.00, 95% CI 0.13 to 69.09).

Intraperitoneal immunoglobulin

Coban 2004 reported the use of IP immunoglobulin was associated with a statistically significant reduction in numbers of exchanges executed for the dialysate white cell count to fall below 100/mL (Analysis 13.1 (24 participants): MD -7.30 exchanges, 95% CI -8.12 to -6.48). There were no treatment failures and no relapses in any participants in this study.

Head-to-head studies

Of the 12 studies in which different regimens of IP antibiotics were compared head-to-head, the only statistically significant outcome was reported by de Fijter 2001: rifampicin/ciprofloxacin was better than cephradine in reducing treatment failure (Analysis 14.2.7 (98 participants) RR 0.50, 95% CI 0.28 to 0.89).

Duration of antibiotic treatment

Altmann 1984 compared duration of antibiotic treatment (vancomycin and gentamicin for 10 versus 21 days) and reported uncertain effects on risk of relapse (Analysis 15.1 (49 participants): RR 1.56, 95% CI 0.61 to 3.95). It is noteworthy that five participants, all of whom received more than 21 days of gentamicin, developed clinical evidence of vestibular damage versus no patients who received a 10-day course of treatment.

It was not possible to tabulate a summary of findings because there were insufficient studies for each analysis.

Discussion

Summary of main results

This review found that in generally low-quality evidence, IP antibiotic therapy may lower risks of primary treatment failure compared with IV antibiotics in two small studies.

The benefits of intermittent dosing of some antibiotics (vancomycin, gentamicin, ceftazidime and teicoplanin) compared with continuous therapy in the treatment of peritonitis, and of IP versus oral antibiotics, are uncertain.

In a single small study of participants presenting with a second recurrence of peritonitis, simultaneous catheter removal and replacement was superior to urokinase to reduce risks of relapsing and remitting PD-associated peritonitis. Insufficient data were available to determine if specific antibiotic classes are most effective for reducing treatment failure and relapse, although glycopeptides may improve complete cure rates compared with first generation cephalosporins.

It was unclear if peritoneal lavage improves response to concomitant antimicrobial therapy.

We also found that IP immunoglobulin administration decreased the time for the dialysate inflammatory cell count to fall, but effects on patient-important outcomes, such as treatment failure or risk of relapse, are uncertain. Longer duration of antibiotics had unclear effects on risk of relapse compared with shorter treatment courses, and may increase adverse events.

Oral antibiotics were associated with increased risk of nausea and vomiting compared with IP administration.

Data for automated PD were scant.

Overall completeness and applicability of evidence

Our review revealed a significant paucity of evidence underlying many widely-used and accepted clinical practices in the treatment of peritonitis, a condition that is associated with significant patient morbidity and mortality. Consequently, some aspects of treatment are uncertain, such as duration of antimicrobial therapy and optimal timing of catheter removal. While valuable information was gained from this review, the few available studies at generally high risk of bias resulted in a lack of evidence in many important areas of clinical practice. Studies tended to focus on choice and route of antibiotic without consideration of other variables such as total duration of therapy, drug dose and the role of patient factors, such as comorbidities and residual kidney function. No RCTs have been conducted to determine if early catheter removal is beneficial in patients not responding to therapy. The follow-up period of most studies was 28 days or fewer; therefore, long-term outcomes, such as technique failure and mortality, were not evaluated. Loss of residual kidney function during peritonitis may be accelerated by aminoglycoside therapy (Baker 2003; Shemin 2000) although this has been refuted by a recent study (Badve 2012). As a result of these factors, there is insufficient evidence regarding several aspects of management that are clinically important and this makes the provision of definitive treatment guidelines difficult at the present time.

Quality of the evidence

The risk of bias of included studies was generally moderate-to-high. In particular, inadequate randomisation and concealment methods were common. Definitions of peritonitis, successful treatment, and relapse varied among studies, thereby reducing their comparability. Many studies were conducted in single-centre settings with small patient numbers, and were underpowered to detect short-term (treatment failure and catheter removal), medium-term (relapse and recurrence) or long-term (mortality and technique failure) effects. Similarly, studies did not systematically evaluate adverse events. Hence there was significant potential for type II statistical errors (finding no treatment effect when a treatment effect exists) in most of our analyses. Studies often predated the current era of lower peritonitis rates, newer antibiotic therapies and increased awareness of multiresistant organisms, thereby potentially reducing the applicability of our meta-analyses.

A significant issue was that there was marked heterogeneity among studies of outcome definitions. Treatment failure was variably measured by resolution of symptoms and signs, clearing of dialysate, fall in dialysate white cell count and microbiological eradication of the causative organism. The time frame in which these changes were required to occur also varied, ranging from 48 hours to 28 days. Similarly there was a large degree of variation in the time elapsed after a primary peritonitis episode for a second peritonitis episode to be considered as a relapse (Li 2010).

An additional problem was interaction of endpoints. For example, primary treatment failure often necessitates catheter removal, which is an endpoint in itself. Some studies defined treatment failure as a need to change the antimicrobial agent or catheter removal. In contrast, other studies defined primary failure as ongoing symptoms beyond 48 hours of antibiotic therapy, with catheter removal evaluated as a separate outcome. These factors reduced the comparability of studies.

Potential biases in the review process

While the review was completed according to standardised Cochrane methodology, potential biases in the review process should be considered. We completed a formal search designed by a specialist information manager including data from a wide range of sources, including handsearching, to limit the potential for omission of potentially relevant studies, although there is a possibility that relevant studies may have not been included. There were insufficient studies included in most meta-analyses to enable us to examine for potential publication bias. Most studies did not systematically report all relevant patient-centred outcomes, suggesting that data for mortality and other clinical outcomes were incomplete, and summary estimates were potentially unreliable.

Agreements and disagreements with other studies or reviews

As far as we are aware, this remains the only published systematic review of RCTs of all PD-associated peritonitis treatment. A review of antimicrobial treatment of PD-associated peritonitis published in 1991 concluded that the optimal empirical treatment was weekly vancomycin in combination with ceftazidime (Millikin 1991). However, this review predated many of the studies included in this study, and was not confined to RCTs.

The mainstay of peritonitis treatment is timely administration of empirical antimicrobial agents that are likely to eradicate the most common causative agents. This is endorsed by guidelines of the International Society of Peritoneal Dialysis (ISPD) (Li 2010) and the Australian and New Zealand Society of Nephrology (Caring for Australians with Renal Impairment - CARI, CARI 2005), both of which state that broad spectrum antibiotic agents designed to cover both gram negative and gram positive organisms should be initiated at the time a diagnosis of peritonitis is suspected. There is, however, insufficient evidence to suggest more specific agents. This has been demonstrated by this review in which we found that in 21 studies comparing different antibiotic classes, the treatment failure rates were generally in the range of 10% to 30%, with only three studies showing a difference between treatment arms (de Fijter 2001; Flanigan 1991; Lupo 1997). In each of these cases the applicability to current practice is low. de Fijter 2001 found IP ciprofloxacin and rifampicin to be superior to IP cephradine. However, monotherapy with a first generation cephalosporin is uncommon, and in this case, was associated with a low initial response rate of 50%. Furthermore, the broad spectrum of action of both ciprofloxacin and rifampicin predisposes to emergence of multiresistant organisms thereby reducing their desirability as first line agents. In our meta-analysis of two studies comparing IP cephazolin and vancomycin we found vancomycin to be superior. However, this result was strongly influenced by a larger number of patients in Flanigan 1991, in which the cephazolin dose of 50 mg/L was two and a half times less than that recommended in the current ISPD guidelines (Li 2010).

Similar efficacy rates amongst several antibiotic regimens facilitate consideration of logistical factors and adverse effect profiles when selecting antibiotics (Kan 2003). Current ISPD guidelines state that there should be centre-specific selection of agents according to local causative micro-organism and resistance patterns (Li 2010). The impact of local microbial resistance on peritonitis outcomes was apparent in two studies comparing oral and IP quinolone use (Cheng 1993; Cheng 1997). In these studies, response rates were low for both treatment arms (41.7% and 55.6% in the oral groups and 66.7% and 70.6% in the IP groups respectively). Micro-organism resistance to quinolones was the major cause of treatment failure, and previous exposure to quinolones was a risk factor for infection with resistant micro-organisms. The emergence of vancomycin-resistant enterococcus is also associated with use of broad spectrum antibiotics (Carmeli 2002; Oprea 2004). Of note increasing prevalence of methicillin-resistant Staphylococci (both S. aureus and coagulase negative species) is a relatively recent phenomenon hence limiting the ability of early studies to evaluate this problem.

In this review, we found that studies in which antibiotics (ciprofloxacin, ofloxacin and cephradine) were administered either orally or IP showed no difference in outcomes for the two routes of administration. However, initial antibiotic therapy is commonly administered intraperitoneally as this theoretically achieves higher dialysate antibiotic levels than permitted with other routes. Evidence about the relative importance of dialysate antibiotic levels was unclear (reviewed in Johnson 2011). In the study of oral versus IP ciprofloxacin included in this review, dialysate antibiotic levels were lower in the IP group but this did not affect patient outcomes (Cheng 1993). Booranalertpaisarn 2003 reported that daily dosing of ceftazidime in patients with peritonitis led to serum levels that were above the recommended minimum inhibitory concentration (MIC) throughout 24 hours, whereas dialysate levels were below the MIC for several hours on days one and four. Despite this, the response rate was 90%, suggesting that achieving therapeutic dialysate levels may not be necessary for treatment to be effective.

Benefits of intermittent (daily) dosing of antibiotics include facilitation of outpatient management and continuation of APD. In the general population, daily dosing with aminoglycosides reduces the risk of ototoxicity compared with intermittent dosing (Deamer 1996). In this review, intermittent and continuous antibiotic dosing had similar outcomes. Adequate duration of antibiotic activity with daily dosing is facilitated by long drug half-lives. Studies of CAPD patients without peritonitis have shown that serum and dialysate levels of several antibiotics remain above the mean inhibitory concentration for up to 48 hours (Grabe 1999; Manley 1999). Many drugs have peak serum levels six hours after administration suggesting that this should be the minimum dwell time. Post-antibiotic effects of drugs may also contribute to the efficacy of intermittent dosing. The applicability of results from studies of intermittent drug therapy in CAPD to APD is however unclear as drug half-lives are greater and clearances more rapid in cycler dwells compared to non-cycler dwells (Manley 2002).

The high rate of complications arising from peritonitis despite rapid institution of antibiotic therapy suggests a need exists for adjuvant treatment strategies. One such treatment is administration of IP urokinase, the rationale being to dissolve fibrin and enable access of antibiotics to entrapped bacteria (Pickering 1989). Williams 1989 showed that urokinase was inferior to simultaneous catheter removal and replacement. However, catheter removal could in itself be considered treatment failure. Meta-analysis of three other studies showed no statistically significant difference in outcomes between urokinase and catheter removal. However, it is noteworthy that in Tong 2005a, the actual number of patients achieving a primary response was five more in the urokinase than the control group, and there were three fewer catheter removals. Furthermore, adequately powered, studies in this area may be beneficial, in which the optimal outcome would be permanent transfer to haemodialysis.

Peritoneal lavage is performed at many centres because it has the potential to remove inflammatory cells and micro-organisms from the peritoneal cavity while providing symptomatic relief, and has been used successfully in abdominal surgery (O'Brien 1987). It has however been the subject of only one RCT (Ejlersen 1991), in which patients with hypotension and shock, the same group in which lavage has been used in surgical settings, were excluded. In this study, peritoneal lavage did not improve response rates. This may be a true effect due to inadvertent removal of macrophages and other components of the immune system thereby a reduction of local host defences against infection. However, further studies to evaluate this therapy further may be useful.

A novel strategy is administration of IP immunoglobulin in conjunction with antibiotics with the aim of improving local host defences (Carozzi 1988). In a study of 24 patients (Coban 2004) biochemical and clinical parameters of improvement were achieved sooner, and the duration of antibiotic therapy was shorter in the immunoglobulin treatment group. The response rate of 100% was unusually high and there were no relapses during three months of follow-up. In a larger population, a difference in response rates may have become apparent.

Authors' conclusions

Implications for practice

In conclusion, currently available evidence from RCTs is not robust and does not identify an optimal antibiotic regimen for the treatment of PD-associated peritonitis.

  • Available studies are small, and generally at high risk of bias, lowering the certainty of treatment effects for all available treatments.

  • At the present time, broad spectrum antibiotics should be initiated at the time a diagnosis of peritonitis is made and IP routes and use of glycopeptides may improve outcomes.

  • Intermittent antibiotic dosing appears to be as effective as continuous dosing, however, the applicability of this practice to APD is unclear.

  • There appears to be no role for adjunctive therapies such as urokinase and peritoneal lavage.

  • When choosing antibiotics, the side-effect profile, local drug resistance patterns and previous antibiotic use and infection history in the individual concerned should be considered. Oral antibiotics may increase risks of nausea and vomiting compared with IP administration.

  • IP route of administration may be superior to IV dosing in preventing primary treatment failures.

  • Few data were available on the pharmacokinetics of many commonly used antibiotics when administered intraperitoneally, and information about many new antibiotics is lacking. Data for automated PD were scant.

  • In cases of recurrent peritonitis, dialysis catheters should be removed rather than using IP urokinase.

Currently available evidence from RCTs is inadequate in many areas of clinical practice important in the management of PD-associated peritonitis and is a limiting factor in the provision of definitive treatment guidelines.

Implications for research

Future research should be adequately powered to assess outcomes such as catheter removal and mortality, and should include long-term follow-up of parameters such as ultrafiltration failure, loss of residual kidney function and technique failure.

Further studies are needed to:

  • Establish the most effective treatment for PD-associated peritonitis. An essential feature of such studies is inclusion of enough patients to ensure adequate power to assess meaningful long- and short-term outcomes. Short-term outcomes should extend beyond whether cure is achieved without catheter removal, for example duration of systemic inflammation. Study of long-term outcomes should include permanent transfer to haemodialysis, development of ultrafiltration failure patient death and late recurrent episodes of peritonitis beyond four weeks from the original episode.

  • Identify specific interventions that would be of value including early versus late catheter removal. Studies designed to study infections due to specific organisms would also be valuable. An example is a study of glycopeptide versus cephalosporin therapy in peritonitis due to coagulase negative Staphylococcal species. Most studies have included patients on CAPD rather than APD, hence, studies designed to test the efficacy of antibiotics in APD are required. This is particularly applicable to studies of intermittent versus continuous dosing when cycler dwell times may well influence pharmacokinetics. Additional studies including greater numbers of participants comparing IP versus IV dosing of the same antibiotic would also assist in assessing meaningful treatment effects.

In addition, future research should be conducted using standard definitions, with inclusion of information about factors that may influence the response to therapy such as prophylaxis regimens and dialysis solutions used. Current ISPD guidelines provide a comprehensive list of requirements for future studies that should be referred to when designing studies.

Acknowledgements

We would like to thank the referees for their comments and feedback during the preparation of this review.

We would like to thank Narelle Willis and Ruth Mitchell from the Cochrane Renal Group for their assistance to update this review.

We would also like to thank Dr Martin Searle from the Department of Nephrology at Christchurch Hospital for his contribution to the updated review.

Data and analyses

Download statistical data

Comparison 1. Intravenous (IV) versus intraperitoneal (IP) antibiotics
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Primary treatment failure2 Risk Ratio (M-H, Random, 95% CI)Totals not selected
1.1 Vancomycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.2 Vancomycin and tobramycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2 Adverse events2 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2.1 Rash1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.2 Hypotension1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3 Infusion pain1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 1.1.

Comparison 1 Intravenous (IV) versus intraperitoneal (IP) antibiotics, Outcome 1 Primary treatment failure.

Analysis 1.2.

Comparison 1 Intravenous (IV) versus intraperitoneal (IP) antibiotics, Outcome 2 Adverse events.

Analysis 1.3.

Comparison 1 Intravenous (IV) versus intraperitoneal (IP) antibiotics, Outcome 3 Infusion pain.

Comparison 2. Oral versus intraperitoneal (IP) antibiotics (same antibiotic)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Primary treatment failure283Risk Ratio (M-H, Random, 95% CI)1.34 [0.71, 2.56]
2 Relapse283Risk Ratio (M-H, Random, 95% CI)3.38 [0.74, 15.35]
3 Failure to achieve complete cure283Risk Ratio (M-H, Random, 95% CI)1.66 [0.98, 2.83]
4 Catheter removal1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
5 Hospitalisation rate1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
6 Adverse events1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
6.1 Nausea and vomiting1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
Analysis 2.1.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 1 Primary treatment failure.

Analysis 2.2.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 2 Relapse.

Analysis 2.3.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 3 Failure to achieve complete cure.

Analysis 2.4.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 4 Catheter removal.

Analysis 2.5.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 5 Hospitalisation rate.

Analysis 2.6.

Comparison 2 Oral versus intraperitoneal (IP) antibiotics (same antibiotic), Outcome 6 Adverse events.

Comparison 3. Oral versus intraperitoneal (IP) antibiotics (different antibiotics)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure8510Risk Ratio (M-H, Random, 95% CI)1.06 [0.80, 1.40]
1.1 Oral quinolone versus aminoglycoside/glycopeptide (IP)5304Risk Ratio (M-H, Random, 95% CI)1.19 [0.83, 1.72]
1.2 Oral quinolone versus cephalosporin (IP)2148Risk Ratio (M-H, Random, 95% CI)1.00 [0.55, 1.81]
1.3 Oral cephradine versus cefuroxime (IP)158Risk Ratio (M-H, Random, 95% CI)0.77 [0.40, 1.46]
2 Primary treatment failure7472Risk Ratio (M-H, Random, 95% CI)1.04 [0.68, 1.59]
2.1 Oral quinolone versus aminoglycoside/glycopeptide (IP)5304Risk Ratio (M-H, Random, 95% CI)1.13 [0.66, 1.94]
2.2 Oral quinolone versus cephalosporin (IP)1110Risk Ratio (M-H, Random, 95% CI)1.04 [0.47, 2.33]
2.3 Oral cephradine versus cefuroxime (IP)158Risk Ratio (M-H, Random, 95% CI)0.6 [0.16, 2.28]
3 Relapse5304Risk Ratio (M-H, Random, 95% CI)1.17 [0.64, 2.15]
4 Catheter removal2170Risk Ratio (M-H, Random, 95% CI)1.18 [0.49, 2.87]
5 Hospitalisation rate1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
6 All-cause mortality1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
7 Microbiological eradication1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
7.1 Oral quinolone versus aminoglycoside/glycopeptide (IP)1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
8 Adverse events3 Risk Ratio (M-H, Random, 95% CI)Subtotals only
8.1 Nausea/vomiting (oral quinolone versus aminoglycoside/glycopeptide (IP))3158Risk Ratio (M-H, Random, 95% CI)9.91 [1.89, 51.99]
8.2 Abdominal swelling or pseudo-obstruction160Risk Ratio (M-H, Random, 95% CI)1.0 [0.07, 15.26]
8.3 Hypotension160Risk Ratio (M-H, Random, 95% CI)0.33 [0.01, 7.87]
8.4 Lethargy150Risk Ratio (M-H, Random, 95% CI)3.0 [0.13, 70.30]
8.5 Myalgia150Risk Ratio (M-H, Random, 95% CI)3.0 [0.13, 70.30]
Analysis 3.1.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 1 Failure to achieve complete cure.

Analysis 3.2.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 2 Primary treatment failure.

Analysis 3.3.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 3 Relapse.

Analysis 3.4.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 4 Catheter removal.

Analysis 3.5.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 5 Hospitalisation rate.

Analysis 3.6.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 6 All-cause mortality.

Analysis 3.7.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 7 Microbiological eradication.

Analysis 3.8.

Comparison 3 Oral versus intraperitoneal (IP) antibiotics (different antibiotics), Outcome 8 Adverse events.

Comparison 4. Any oral versus any intraperitoneal (IP)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Treatment failure9555Risk Ratio (M-H, Random, 95% CI)1.12 [0.79, 1.60]
1.1 Different7472Risk Ratio (M-H, Random, 95% CI)1.04 [0.68, 1.59]
1.2 Same283Risk Ratio (M-H, Random, 95% CI)1.34 [0.71, 2.56]
Analysis 4.1.

Comparison 4 Any oral versus any intraperitoneal (IP), Outcome 1 Treatment failure.

Comparison 5. Low versus high dose antibiotic
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2 Relapse1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
3 Seizures1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 5.1.

Comparison 5 Low versus high dose antibiotic, Outcome 1 Failure to achieve complete cure.

Analysis 5.2.

Comparison 5 Low versus high dose antibiotic, Outcome 2 Relapse.

Analysis 5.3.

Comparison 5 Low versus high dose antibiotic, Outcome 3 Seizures.

Comparison 6. Intermittent versus continuous antibiotics
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure4338Risk Ratio (M-H, Random, 95% CI)0.92 [0.64, 1.33]
1.1 Gentamicin1100Risk Ratio (M-H, Random, 95% CI)0.79 [0.45, 1.37]
1.2 Vancomycin272Risk Ratio (M-H, Random, 95% CI)0.62 [0.18, 2.11]
1.3 Tecioplanin/ceftazidime186Risk Ratio (M-H, Random, 95% CI)1.23 [0.53, 2.90]
1.4 Vancomycin/ceftazidime180Risk Ratio (M-H, Random, 95% CI)1.09 [0.55, 2.18]
2 Primary treatment failure5522Risk Ratio (M-H, Random, 95% CI)1.11 [0.77, 1.62]
2.1 Gentamicin1100Risk Ratio (M-H, Random, 95% CI)0.67 [0.26, 1.73]
2.2 Vancomycin272Risk Ratio (M-H, Random, 95% CI)1.1 [0.08, 15.36]
2.3 Teicoplanin/ceftazidime186Risk Ratio (M-H, Random, 95% CI)4.39 [0.51, 37.69]
2.4 Vancomycin/ceftazidime180Risk Ratio (M-H, Random, 95% CI)1.6 [0.57, 4.47]
2.5 Cefazolin/tobramycin1184Risk Ratio (M-H, Random, 95% CI)1.10 [0.70, 1.73]
3 Relapse4338Risk Ratio (M-H, Random, 95% CI)0.76 [0.45, 1.28]
3.1 Gentamicin1100Risk Ratio (M-H, Random, 95% CI)0.9 [0.40, 2.02]
3.2 Vancomycin272Risk Ratio (M-H, Random, 95% CI)0.53 [0.13, 2.11]
3.3 Teicoplanin/ceftazidime186Risk Ratio (M-H, Random, 95% CI)0.78 [0.27, 2.28]
3.4 Vancomycin/ceftazidime180Risk Ratio (M-H, Random, 95% CI)0.67 [0.20, 2.18]
4 Catheter removal1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
5 Rash1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
5.1 Vancomycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
Analysis 6.1.

Comparison 6 Intermittent versus continuous antibiotics, Outcome 1 Failure to achieve complete cure.

Analysis 6.2.

Comparison 6 Intermittent versus continuous antibiotics, Outcome 2 Primary treatment failure.

Analysis 6.3.

Comparison 6 Intermittent versus continuous antibiotics, Outcome 3 Relapse.

Analysis 6.4.

Comparison 6 Intermittent versus continuous antibiotics, Outcome 4 Catheter removal.

Analysis 6.5.

Comparison 6 Intermittent versus continuous antibiotics, Outcome 5 Rash.

Comparison 7. First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure3370Risk Ratio (M-H, Random, 95% CI)1.66 [1.01, 2.72]
1.1 Vancomycin-based regimen2305Risk Ratio (M-H, Random, 95% CI)1.51 [1.03, 2.22]
1.2 Teicoplanin-based regimen165Risk Ratio (M-H, Random, 95% CI)4.63 [1.04, 20.58]
2 Primary treatment failure2 Risk Ratio (M-H, Random, 95% CI)Subtotals only
2.1 Vancomycin-based regimen2305Risk Ratio (M-H, Random, 95% CI)1.14 [0.69, 1.87]
3 Relapse3350Risk Ratio (M-H, Random, 95% CI)1.68 [0.84, 3.36]
3.1 Vancomycin-based regimen2305Risk Ratio (M-H, Random, 95% CI)1.62 [0.69, 3.79]
3.2 Teicoplanin-based regimen145Risk Ratio (M-H, Random, 95% CI)1.37 [0.09, 20.52]
4 Catheter removal2305Risk Ratio (M-H, Random, 95% CI)0.95 [0.41, 2.19]
5 Microbiological eradication1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 7.1.

Comparison 7 First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen, Outcome 1 Failure to achieve complete cure.

Analysis 7.2.

Comparison 7 First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen, Outcome 2 Primary treatment failure.

Analysis 7.3.

Comparison 7 First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen, Outcome 3 Relapse.

Analysis 7.4.

Comparison 7 First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen, Outcome 4 Catheter removal.

Analysis 7.5.

Comparison 7 First generation cephalosporin versus glycopeptide-based intraperitoneal (IP) antibiotic regimen, Outcome 5 Microbiological eradication.

Comparison 8. Teicoplanin versus vancomycin-based intraperitoneal (IP) antibiotic regimen
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Primary treatment failure2178Risk Ratio (M-H, Random, 95% CI)0.36 [0.13, 0.96]
2 Failure to achieve complete cure2178Risk Ratio (M-H, Random, 95% CI)0.67 [0.40, 1.15]
3 Relapse2178Risk Ratio (M-H, Random, 95% CI)1.01 [0.49, 2.11]
Analysis 8.1.

Comparison 8 Teicoplanin versus vancomycin-based intraperitoneal (IP) antibiotic regimen, Outcome 1 Primary treatment failure.

Analysis 8.2.

Comparison 8 Teicoplanin versus vancomycin-based intraperitoneal (IP) antibiotic regimen, Outcome 2 Failure to achieve complete cure.

Analysis 8.3.

Comparison 8 Teicoplanin versus vancomycin-based intraperitoneal (IP) antibiotic regimen, Outcome 3 Relapse.

Comparison 9. Comparison of two oral antibiotic regimens
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2 Catheter removal1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
3 Change in antibiotics following culture results1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
4 Adverse events1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
4.1 Nausea and vomiting1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
4.2 Rash1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
Analysis 9.1.

Comparison 9 Comparison of two oral antibiotic regimens, Outcome 1 Failure to achieve complete cure.

Analysis 9.2.

Comparison 9 Comparison of two oral antibiotic regimens, Outcome 2 Catheter removal.

Analysis 9.3.

Comparison 9 Comparison of two oral antibiotic regimens, Outcome 3 Change in antibiotics following culture results.

Analysis 9.4.

Comparison 9 Comparison of two oral antibiotic regimens, Outcome 4 Adverse events.

Comparison 10. Fibrinolytic agents versus non-urokinase or placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2 Primary treatment failure (persistent peritonitis)299Risk Ratio (M-H, Random, 95% CI)0.63 [0.32, 1.26]
3 Relapse3 Risk Ratio (M-H, Random, 95% CI)Subtotals only
3.1 Persistent peritonitis2101Risk Ratio (M-H, Random, 95% CI)0.51 [0.22, 1.17]
3.2 Peritonitis commencement180Risk Ratio (M-H, Random, 95% CI)1.33 [0.32, 5.58]
4 Catheter removal2168Risk Ratio (M-H, Random, 95% CI)0.70 [0.37, 1.30]
4.1 Persistent peritonitis188Risk Ratio (M-H, Random, 95% CI)0.77 [0.38, 1.57]
4.2 Peritonitis commencement180Risk Ratio (M-H, Random, 95% CI)0.5 [0.13, 1.86]
5 All-cause mortality1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 10.1.

Comparison 10 Fibrinolytic agents versus non-urokinase or placebo, Outcome 1 Failure to achieve complete cure.

Analysis 10.2.

Comparison 10 Fibrinolytic agents versus non-urokinase or placebo, Outcome 2 Primary treatment failure (persistent peritonitis).

Analysis 10.3.

Comparison 10 Fibrinolytic agents versus non-urokinase or placebo, Outcome 3 Relapse.

Analysis 10.4.

Comparison 10 Fibrinolytic agents versus non-urokinase or placebo, Outcome 4 Catheter removal.

Analysis 10.5.

Comparison 10 Fibrinolytic agents versus non-urokinase or placebo, Outcome 5 All-cause mortality.

Comparison 11. Urokinase versus simultaneous catheter removal or replacement
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Recurrence of peritonitis1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 11.1.

Comparison 11 Urokinase versus simultaneous catheter removal or replacement, Outcome 1 Recurrence of peritonitis.

Comparison 12. Peritoneal lavage
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2 Relapse1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
3 Technique failure1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
4 Adverse events1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 12.1.

Comparison 12 Peritoneal lavage, Outcome 1 Failure to achieve complete cure.

Analysis 12.2.

Comparison 12 Peritoneal lavage, Outcome 2 Relapse.

Analysis 12.3.

Comparison 12 Peritoneal lavage, Outcome 3 Technique failure.

Analysis 12.4.

Comparison 12 Peritoneal lavage, Outcome 4 Adverse events.

Comparison 13. Intraperitoneal immunoglobulin
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Number of exchanges for reduction in dialysate WWC < 100/mL1 Mean Difference (IV, Random, 95% CI)Totals not selected
2 Relapse1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 13.1.

Comparison 13 Intraperitoneal immunoglobulin, Outcome 1 Number of exchanges for reduction in dialysate WWC < 100/mL.

Analysis 13.2.

Comparison 13 Intraperitoneal immunoglobulin, Outcome 2 Relapse.

Comparison 14. Comparison of two intraperitoneal antibiotic regimens
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Failure to achieve complete cure6 Risk Ratio (M-H, Random, 95% CI)Totals not selected
1.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.2 Cefuroxime verus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.3 Vancomycin/cefotaxime versus/tobramycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.4 Ciproflozacin verus vancomycin/gentamicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.5 Cefazolin/ceftazidime versus cefazolin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
1.6 Cefapime versus cefotaxime1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2 Primary treatment failure8 Risk Ratio (M-H, Random, 95% CI)Totals not selected
2.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.2 Vancomycin/cefotaxime versus/tobramycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.3 Ciproflozacin verus vancomycin/gentamicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.4 Cephazolin/netilmicin versus vancomycin/ceftazidine1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.5 Cefuroxime versus teicoplanin/aztreonam1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.6 Cefazolin/ceftazidime versus imipenem1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.7 Ceiprofloxacin/rifampicin versus cephradine1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.8 Gentamicin/methicillin versus clindamycin/mezlocillin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.9 Gentamicin/methicillin versus gentamicin/cloxacillin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
2.10 Gentamicin/cloxacillin verus clindamycin/mezlocillin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3 Relapse6 Risk Ratio (M-H, Random, 95% CI)Totals not selected
3.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3.2 Vancomycin/cefotaxime versus/tobramycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3.3 Ciproflozacin verus vancomycin/gentamicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3.4 Cefuroxime versus teicoplanin/aztreonam1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3.5 Cefazolin/ceftazidime versus cefazolin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
3.6 Ceiprofloxacin/rifampicin versus cephradine1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
4 Death due to peritonitis1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
4.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
5 Hospitalisation rate1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
5.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
6 Infusion pain1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
6.1 Cefepime versus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7 Catheter removal6 Risk Ratio (M-H, Random, 95% CI)Totals not selected
7.1 Cefuroxime verus vancomycin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.2 Vancomycin/cefotaxime versus/tobramycin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.3 Ciproflozacin verus vancomycin/gentamicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.4 Cefazolin/ceftazidime versus imipenem1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.5 Cefazolin/ceftazidime versus cefazolin/netilmicin1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
7.6 Ceiprofloxacin/rifampicin versus cephradine1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
8 All-cause mortality1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
8.1 Cefuroxime versus teicoplanin/aztreonam1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
9 Microbiological eradication1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
9.1 Ceiprofloxacin/rifampicin versus cephradine1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
10 Adverse events1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
10.1 Gastrointestinal toxicity1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
10.2 Rash1 Risk Ratio (M-H, Random, 95% CI)0.0 [0.0, 0.0]
Analysis 14.1.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 1 Failure to achieve complete cure.

Analysis 14.2.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 2 Primary treatment failure.

Analysis 14.3.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 3 Relapse.

Analysis 14.4.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 4 Death due to peritonitis.

Analysis 14.5.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 5 Hospitalisation rate.

Analysis 14.6.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 6 Infusion pain.

Analysis 14.7.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 7 Catheter removal.

Analysis 14.8.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 8 All-cause mortality.

Analysis 14.9.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 9 Microbiological eradication.

Analysis 14.10.

Comparison 14 Comparison of two intraperitoneal antibiotic regimens, Outcome 10 Adverse events.

Comparison 15. Intravenous (IV) vancomycin and dialysate gentamicin: 21 days versus 10 days
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Relapse1 Risk Ratio (M-H, Random, 95% CI)Totals not selected
Analysis 15.1.

Comparison 15 Intravenous (IV) vancomycin and dialysate gentamicin: 21 days versus 10 days, Outcome 1 Relapse.

Appendices

Appendix 1. Electronic search strategies

DatabaseSearch terms
CENTRAL#1 PERITONEAL DIALYSIS
#2 (peritoneal next dialysis)
#3 pd
#4 capd
#5 ccpd
#6 (#1 or #2 or #3 or #4 or #5)
#7 PERITONITIS
#8 peritonitis
#9 periton*
#10 infect*
#11 (#9 and #10)
#12 PERITONEUM
#13 BACTERIAL INFECTIONS AND MYCOSES
#14 (#12 and #13)
#15 (#7 or #8 or #11 or #14)
#16 (#6 and #15)
MEDLINE1. exp peritoneal dialysis/
2. peritoneal dialysis.tw.
3. (PD or CAPD or CCPD).tw.
4. or/1-3
5. Peritonitis/
6. peritonitis.tw.
7. (periton$ and infect$).tw.
8. exp Peritoneum/
9. exp "bacterial infections and mycoses"/
10. 8 and 9
11. or/5-7,10
12. 4 and 11
EMBASE1. continuous ambulatory peritoneal dialysis/ or peritoneal dialysis/
2. peritoneal dialysis.tw.
3. (PD or CAPD or CCPD).tw.
4. or/1-3
5. exp Peritonitis/
6. peritonitis.tw.
7. (periton$ and infect$).tw.
8. exp peritoneal cavity/ or exp peritoneum/
9. exp Infection/
10. 8 and 9
11. or/5-7,10
12. 4 and 11

Appendix 2. Risk of bias assessment tool

Potential source of bias Assessment criteria

Random sequence generation

Selection bias (biased allocation to interventions) due to inadequate generation of a randomised sequence

Low risk of bias: Random number table; computer random number generator; coin tossing; shuffling cards or envelopes; throwing dice; drawing of lots; minimization (minimization may be implemented without a random element, and this is considered to be equivalent to being random).
High risk of bias: Sequence generated by odd or even date of birth; date (or day) of admission; sequence generated by hospital or clinic record number; allocation by judgement of the clinician; by preference of the participant; based on the results of a laboratory test or a series of tests; by availability of the intervention.
Unclear: Insufficient information about the sequence generation process to permit judgement.

Allocation concealment

Selection bias (biased allocation to interventions) due to inadequate concealment of allocations prior to assignment

Low risk of bias: Randomisation method described that would not allow investigator/participant to know or influence intervention group before eligible participant entered in the study (e.g. central allocation, including telephone, web-based, and pharmacy-controlled, randomisation; sequentially numbered drug containers of identical appearance; sequentially numbered, opaque, sealed envelopes).
High risk of bias: Using an open random allocation schedule (e.g. a list of random numbers); assignment envelopes were used without appropriate safeguards (e.g. if envelopes were unsealed or non-opaque or not sequentially numbered); alternation or rotation; date of birth; case record number; any other explicitly unconcealed procedure.
Unclear: Randomisation stated but no information on method used is available.

Blinding of participants and personnel

Performance bias due to knowledge of the allocated interventions by participants and personnel during the study

Low risk of bias: No blinding or incomplete blinding, but the review authors judge that the outcome is not likely to be influenced by lack of blinding; blinding of participants and key study personnel ensured, and unlikely that the blinding could have been broken.
High risk of bias: No blinding or incomplete blinding, and the outcome is likely to be influenced by lack of blinding; blinding of key study participants and personnel attempted, but likely that the blinding could have been broken, and the outcome is likely to be influenced by lack of blinding.
Unclear: Insufficient information to permit judgement

Blinding of outcome assessment

Detection bias due to knowledge of the allocated interventions by outcome assessors.

Low risk of bias: No blinding of outcome assessment, but the review authors judge that the outcome measurement is not likely to be influenced by lack of blinding; blinding of outcome assessment ensured, and unlikely that the blinding could have been broken.
High risk of bias: No blinding of outcome assessment, and the outcome measurement is likely to be influenced by lack of blinding; blinding of outcome assessment, but likely that the blinding could have been broken, and the outcome measurement is likely to be influenced by lack of blinding.
Unclear: Insufficient information to permit judgement

Incomplete outcome data

Attrition bias due to amount, nature or handling of incomplete outcome data.

Low risk of bias: No missing outcome data; reasons for missing outcome data unlikely to be related to true outcome (for survival data, censoring unlikely to be introducing bias); missing outcome data balanced in numbers across intervention groups, with similar reasons for missing data across groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk not enough to have a clinically relevant impact on the intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes not enough to have a clinically relevant impact on observed effect size; missing data have been imputed using appropriate methods.
High risk of bias: Reason for missing outcome data likely to be related to true outcome, with either imbalance in numbers or reasons for missing data across intervention groups; for dichotomous outcome data, the proportion of missing outcomes compared with observed event risk enough to induce clinically relevant bias in intervention effect estimate; for continuous outcome data, plausible effect size (difference in means or standardized difference in means) among missing outcomes enough to induce clinically relevant bias in observed effect size; ‘as-treated’ analysis done with substantial departure of the intervention received from that assigned at randomisation; potentially inappropriate application of simple imputation.
Unclear: Insufficient information to permit judgement

Selective reporting

Reporting bias due to selective outcome reporting

Low risk of bias: The study protocol is available and all of the study’s pre-specified (primary and secondary) outcomes that are of interest in the review have been reported in the pre-specified way; the study protocol is not available but it is clear that the published reports include all expected outcomes, including those that were pre-specified (convincing text of this nature may be uncommon).
High risk of bias: Not all of the study’s pre-specified primary outcomes have been reported; one or more primary outcomes is reported using measurements, analysis methods or subsets of the data (e.g. subscales) that were not pre-specified; one or more reported primary outcomes were not pre-specified (unless clear justification for their reporting is provided, such as an unexpected adverse effect); one or more outcomes of interest in the review are reported incompletely so that they cannot be entered in a meta-analysis; the study report fails to include results for a key outcome that would be expected to have been reported for such a study.
Unclear: Insufficient information to permit judgement

Other bias

Bias due to problems not covered elsewhere in the table

Low risk of bias: The study appears to be free of other sources of bias.
High risk of bias: Had a potential source of bias related to the specific study design used; stopped early due to some data-dependent process (including a formal-stopping rule); had extreme baseline imbalance; has been claimed to have been fraudulent; had some other problem.
Unclear: Insufficient information to assess whether an important risk of bias exists; insufficient rationale or evidence that an identified problem will introduce bias.

What's new

Last assessed as up-to-date: 5 March 2014.

DateEventDescription
2 May 2014AmendedMinor copy edits made to study names to match Renal Group's Specialised Register

History

Protocol first published: Issue 2, 2005
Review first published: Issue 1, 2008

DateEventDescription
5 March 2014New search has been performedReview updated
5 March 2014New citation required and conclusions have changedNew studies identified
11 June 2008AmendedConverted to new review format.

Contributions of authors

Screening of titles and abstracts: AB, KW, GFMS, SP
Study eligibility: AB, KW, GFMS, SP
Risk of bias assessment, data extraction, data analysis: AB, KW, GFMS, SP
Writing of review: AB, KW, GFMS, SP, DJ, JC
Disagreement resolution: DJ, JC

Declarations of interest

Professor David Johnson is a consultant for Baxter Healthcare Pty Ltd and has previously received research funds from this company. He has also received speakers' honoraria and research grants from Fresenius Medical Care. Angela Ballinger received a student stipend for a summer studentship 2011 to 2012 from the University of Otago to assist with completing this research. Suetonia Palmer received a fellowship administered by the Consorzio Mario Negri Sud from Amgen Dompe for assistance with travel for collaboration and supervision. The other authors had no known conflicts of interest.

Sources of support

Internal sources

  • The research team acknowledges the support received from the Cochrane Renal Group in the conduct of this review, Australia.

External sources

  • Suetonia Palmer, New Zealand.

    received an unrestricted fellowship from Amgen Dompe, administered by the Consorzio Mario Negri Sud

  • Angela Ballinger, New Zealand.

    Received a summer student scholarship from the Division of Medical Sciences, Unversity of Otago to complete the update of this review

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Altmann 1984

Methods
  • Study design: RCT

  • Time frame: 28 days

Participants
  • Country: UK

  • Setting: single centre

  • Inclusion criteria: home CAPD patients who presented with uncomplicated peritoneal infection, having been free from peritonitis for 1 month

  • Number: 80

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • 21 days treatment with vancomycin and gentamicin

  • At presentation vancomycin (500 mg IV) and gentamicin (10 mg/L dialysate in alternate bags) was given

Control group

  • 10 days treatment with vancomycin and gentamicin

  • At presentation vancomycin (500 mg IV) and gentamicin (10 mg/L dialysate in alternate bags) was given

Co-interventions

  • At 48 hours, according to bacterial sensitivity, vancomycin (15 mg/L dialysate) of gentamicin were continued; both were continued for "sterile" peritonitis

Outcomes
  • Complete cure

  • Peritonitis relapse

  • Adverse effects (vestibular damage)

Notes

Adverse effects (vestibular damage)

  • 5 patients, all of whom had received at least one 21 day course of gentamicin, developed clinical evidence of vestibular damage; none of those patients who had received only 10 day courses of treatment developed this. The study was therefore terminated

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskUnblinded comparison
Blinding of outcome assessment (detection bias)
All outcomes
High riskUnblinded comparison
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskEarly termination of study and abstract-only publication

Bailie 1987

Methods
  • Study design: RCT

  • Time frame: NS

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: probable CAPD-associated gram-positive peritonitis

  • Number: 20

  • Mean age ± SD (years): NS

  • Sex (M/F): 11/9

  • Exclusion criteria: Suspected of having gram negative peritonitis; an episode of peritonitis within the previous 4 weeks; no organisms on gram stain

Interventions

Treatment group

  • Vancomycin: 1 g IV loading dose then maintenance dose 25 mg/L IP added to each exchange

  • Total duration of therapy: 14 days

Control group

  • Vancomycin: 1 g IP loading dose then maintenance dose 25 mg/L IP added to each exchange

  • Total duration of therapy: 14 days

Outcomes
  • Successful treatment

  • Adverse effects

Notes

Definition of peritonitis

  • The identification of gram-positive organisms on gram stain or any two of abdominal pain, a cloudy dialysate effluent or > 100 WCC/mL of dialysate

Definition of cure

  • Clearing of dialysate; eradication of the organism; disappearance of physical symptoms

Completeness of follow-up

  • Eligible/considered for inclusion: 20

  • Enrolled/randomised: 20

  • Analysed: 20

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of administration of antibiotic loading dose between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Bennett-Jones 1987

Methods
  • Study design: RCT

  • Time frame: NS

  • Follow-up period: 28 days

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: patients receiving CAPD therapy with peritonitis

  • Number: treatment group (36); control group (39)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: associated catheter leak; catheter-tract or severe exit-site infection; fungal peritonitis; septicaemia; bowel perforation; recurrence of peritonitis within 15 days of a previous episode; pre-existing liver disease, diabetes mellitus or epilepsy

Interventions

Treatment group

  • Vancomycin: 0.5 g IV (if body surface area < 1.73 m²) or 1.0 g (if body surface area > 1.73 m²) loading dose then vancomycin 0.5 g on day 6

  • Tobramycin: 1.0 mg/kg IV loading dose then 20 to 60 mg on days 2, 4, 6 depending on serum levels

  • Change to oral antibiotics, depending on culture and sensitivity, at day 4.

Control group

  • Vancomycin: 20 mg/L IP and tobramycin 4 mg/L to every exchange for 10 days; one antibiotic could be discontinued at day 4 depending on culture and sensitivity results

Co-interventions

  • Three rapid exchanges for symptomatic relief then return to usual CAPD regimen

Outcomes
  • Treatment failure

  • Side effects of treatment

Notes

Definition of peritonitis

  • Dialysate WCC > 100/mm³

Definition of cure

  • The resolution of symptoms and signs of peritonitis; dialysate WCC < 100/mm³ within 10 days; absence of a subsequent relapse

Definition of treatment failure

  • Clinical deterioration, or an increase in the dialysate WCC necessitating an alteration in antibiotics administration, continuation of treatment beyond 10 days or catheter removal

Definition of relapse

  • Recurrence, with the same organism or no growth, within 15 days of completion of treatment of the previous episode

Completeness of follow-up

  • Eligible/considered for inclusion: 80

  • Enrolled/randomised: 80

  • Analysed: 75

  • Per cent followed: 93.8%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk5/80 (6.3%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Bennett-Jones 1990

Methods
  • Study design: RCT

  • Time frame: NS

  • Follow-up period: 15 days

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: patients > 18 years with a clinical diagnosis of CAPD peritonitis

  • Number: treatment group (22); control group (26)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: leak of dialysis from the exit site; catheter tunnel infection; pregnancy; no demographic data provided

Interventions

Treatment group

  • Oral ciprofloxacin: 750 mg 3 times for 24 hours then 750 mg orally twice daily; further dose adjustments made if peak plasma levels exceeded 10 mg/L

  • Total duration of treatment: 10 days

Control group

  • Vancomycin: 25 mg/L and gentamicin 8 mg/L for 48 hours then 4 mg/L

  • Total duration of treatment: 10 days

Co-interventions

  • An IV loading dose of study antibiotics was given if the patient was systemically unwell or pyrexial, or peripheral WCC > 12 x 10⁹/L

  • Oral flucloxacillin 500 mg 4 times/d added to either regimen if S. aureus was isolated

Outcomes
  • Treatment failure

  • Recurrence of peritonitis

  • Side effects of treatment

Notes

Definition of peritonitis

  • Cloudy dialysis effluent; > 100 leucocytes/mm³ in dialysis effluent

Definition of treatment failure

  • Dialysate WCC of > 50/mm³ at completion of treatment

Definition of relapse

  • Recurrence of peritonitis within 28 days with either the same organism or no growth

Completeness of follow-up

  • Eligible/considered for inclusion: 61

  • Enrolled/randomised: 51

  • Analysed: 48

  • Per cent followed: 95.1%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk3/51 (5.8%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Boeschoten 1985

Methods
  • Study design: RCT

  • Time frame: January 1980 to January 1983

  • Follow-up period: 2 weeks after completion of treatment

Participants
  • Country: The Netherlands

  • Setting: teaching hospital

  • Inclusion criteria: adult patients receiving CAPD therapy

  • Number: 39

  • Mean age (range): 47 years (21-66)

  • Sex (M/F): 20/19

  • Exclusion criteria: gram-negative rods or yeasts shown on gram-stained film.

Interventions

Treatment group

  • Oral cephradine: 500 mg loading dose then 250 mg orally with each dialysis exchange

  • Treatment continued until 1 week after dialysate WCC < 100/µL and there had been a negative dialysate culture

Control group

  • Cephradine: 500 mg IP loading dose then 250 mg IP

  • Treatment continued until 1 week after dialysate WCC < 100/µL and there had been a negative dialysate culture

Co-interventions

  • Heparin (500 U/L) was added to dialysate as long as the fluid remained cloudy

  • Cephradine replaced by another antibiotic when the causative organism was found to be resistant in vitro

Outcomes
  • Successful treatment

Notes

Definition of peritonitis

  • Cloudy dialysate with WCC > 100/µL with or without abdominal symptoms

Definition of cure

  • Disappearance of symptoms and signs within 48 hours

Definition of treatment failure

  • Persistent clinical symptoms and bacteriological findings

Definition of relapse

  • An episode of peritonitis with the same causative organism after an initial improvement, either during or within 2 weeks after stopping the antibiotics

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote from Methods section of paper: "...patients were randomized according to their date of catheter implantation."
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "...patients were randomized according to their date of catheter implantation."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk45/106 (42.5%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Bowley 1988

Methods
  • Study design: RCT

  • Time frame: NS

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: CAPD-associated peritonitis caused by gram-positive organisms

  • Number: 11 patients (12 episodes of peritonitis)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • Teicoplanin: IP 50 mg/2 L bag for 48 hours then teicoplanin IP 25 mg/2 L bag for a further 5 days

Control group

  • Vancomycin: IP 50 mg/2 L bag for 48 hours then vancomycin IP 25 mg/2 L bag for a further 5 days

Co-interventions

  • Netilmicin: IP 25 mg in alternate bags for 48 hours (both study arms)

  • Two patients with S. aureus infection were also treated with oral clindamycin for 7 days

Outcomes
  • Successful treatment

  • Relapse of peritonitis

Notes

Definition of peritonitis: NS

Definition of cure

  • "Judged by clinical criteria"

Definition of treatment failure: NS

Definition of relapse

  • Further infection with the same organism within 14 days of completion of therapy

Completeness of follow-up

  • Eligible/considered for inclusion: 11

  • Enrolled/randomised: 11

  • Analysed: 11

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Boyce 1988

Methods
  • Study design: parallel RCT

  • Time frame: April 1986 to January 1987

  • Follow-up period: 4 weeks

Participants
  • Country: Australia

  • Setting: teaching hospital

  • Inclusion criteria: all patients who presented with peritonitis

  • Number: 90

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • Vancomycin: 30 mg/kg in a 2 L peritoneal dialysate for a 6 hours dwell; repeated after 1 week

Control group

  • Vancomycin: 1 g IP loading dose then 30 mg/L dialysate continued for 5 days following macroscopic clearing of the dialysate

Co-interventions

  • All patients initially managed with 2 to 3 rapid 2L peritoneal lavages with heparinised dialysate

Outcomes
  • Treatment failure

  • Recurrence of peritonitis

  • Skin rash

Notes

Exclusions post randomisation but pre-intervention

  • All patients with fungal or gram-negative peritonitis were excluded from analysis

Definition of peritonitis

  • Abdominal pain and cloudy dialysate effluent with a peritoneal WCC > 100/µL

Completeness of follow-up

  • Eligible/considered for inclusion: 90

  • Enrolled/randomised: 90

  • Analysed: 51

  • Per cent followed: 56.7%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different frequencies of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk39/90 (43.3%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Chan 1990

Methods
  • Study design: parallel RCT

  • Time frame: 1 October 1987 to 30 September 1998

  • Follow-up period: 28 days

Participants
  • Country: Hong Kong

  • Setting: university department, teaching hospital

  • Inclusion criteria: CAPD peritonitis

  • Number: treatment group 1 (34); treatment group 2 (36); control group (36)

  • Mean age ± SEM (years): treatment group 1 (44 ± 15); treatment group 2 (22 ± 14); control group (53 ± 14)

  • Sex (M/F): treatment group 1 (18/16); treatment group 2 (22/14); control group (21/15)

  • Exclusion criteria: NS

Interventions

Treatment group 1

  • Oral ofloxacin: 400 mg loading dose on the first day then 300 mg/d

  • Total duration of antibiotic therapy: 10 days

Treatment group 2

  • Oral ofloxacin: 400 mg loading dose on the first day then 300 mg/d

  • Oral rifampicin: 300 mg/d

  • Total duration of antibiotic therapy: 10 days

Control group

  • Cephalothin 250 mg/L IP and tobramycin 8 mg/L

  • Total duration of antibiotic therapy: 10 days

Co-interventions

  • Two rapid 1 hour exchanges were performed at the time of diagnosis in all patients

Further peritoneal lavage (rate 1 L/h) was performed in 25 patients

Outcomes
  • Treatment failure

  • Catheter removal

  • Side effects of treatment

Notes

Exclusions post randomisation but pre-intervention

  • Fungal peritonitis (5); tuberculous peritonitis (1)

Definition of peritonitis

  • Abdominal pain and cloudy effluent with or without fever; patients who responded initially but had another episode more than 28 days after the onset of the first episode were considered to have a new infection and entered into the study as a separate episode

Definition of cure

  • Complete resolution of symptoms and signs and negative bacterial cultures on repeat sampling, including day 28

Definition of treatment failure

  • Any episode that required a change in antibiotic therapy

Definition of relapse

  • Repeat infection within 28 days of receiving treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 117 episodes of peritonitis in 85 patients

  • Enrolled/randomised: 117

  • Analysed: 110

  • Per cent followed: 94.9%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "...antibiotic regimens were given code numbers....(which) were then randomly arranged in a table."
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different numbers and routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskWithdrawal occurred due to 3 episodes of fungal peritonitis in group 1 but only 1 episode in each of groups 2 and 3, indicating possible attrition bias
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Cheng 1991

Methods
  • Study design: RCT

  • Time frame: NS

  • Follow-up period: 28 days after treatment

Participants
  • Country: Hong Kong

  • Setting: multicentre, teaching hospital, university hospital

  • Inclusion criteria: patients on CAPD who developed peritonitis

  • Number: treatment group (23); control group (25)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: known sensitivity to quinolones, vancomycin and aztreonam; peritonitis secondary to fungi; tuberculous peritonitis; relapsing peritonitis

Interventions

Treatment group

  • Oral ofloxacin: 400 mg loading dose then 300 mg/d for 10 days

Control group

  • Vancomycin: 500 mg/L IP loading dose then 30 mg/L IP maintenance dose

  • Aztreonam: 500 mg/L IP loading dose then 250 mg/L IP maintenance dose

Co-interventions

  • 3 flushes with 1 L 1.5% solution prior to the beginning of treatment if the peritoneal effluent was very turbid

Outcomes
  • Treatment failure

  • Relapse of peritonitis

  • All-cause mortality

  • Hospitalisation (number of patients and duration of stay)

  • Side effects of treatment

Notes

Exclusions post randomisation but pre-intervention

  • 3 patients (2 transfers to other hospitals, 1 case of fungal peritonitis)

Definition of peritonitis

  • Abdominal pain and cloudy peritoneal dialysate occurred with or without fever; peritoneal WCC > 200/mm³ with > 50% polymorphs

Definition of treatment failure

  • Persistent fever, abdominal pain and cloudy effluent, less than 50% reduction in the total WCC compared to the pretreatment value after 3 days of antibiotic treatment

Definition of relapse

  • Recurrence of peritonitis with the same organism within 18 days after stopping treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 48 episodes of peritonitis

  • Enrolled/randomised: 48

  • Analysed: 45

  • Per cent followed: 93.8%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "Patients...were randomised...by referring to a table of random numbers."
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "Patients...were randomised...by referring to a table of random numbers."
Blinding of participants and personnel (performance bias)
All outcomes
Low riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk3/46 (6.5%) patients lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Cheng 1993

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 28 days

Participants
  • Country: Hong Kong

  • Setting: teaching hospital, university hospital

  • Inclusion criteria: patients on CAPD who developed peritonitis

  • Number: 46

  • Age and sex: groups were comparable with regards to age and sex (data not shown)

  • Exclusion criteria: known sensitivity to fluoroquinolones; peritonitis secondary to fungi; tuberculous peritonitis; relapsing peritonitis

Interventions

Treatment group

  • Oral ciprofloxacin: 750 mg twice daily

  • Total duration of treatment: 10 days

Control group

  • Ciprofloxacin: 200 mg IP in the first bag then 25 mg/L in subsequent bags

  • Total duration of treatment: 10 days

Additional treatment

  • Patients randomised to oral ciprofloxacin with primary treatment failure were given IP ciprofloxacin if the micro-organism was sensitive on culture, or it was a culture negative episode

  • Patients randomised to IP ciprofloxacin were changed to IP vancomycin and amikacin

Outcomes
  • Treatment failure

  • Relapse

  • Catheter removal

  • Hospitalisation (number of patients and duration of stay)

  • Side effects of treatment

Notes

Exclusions post randomisation but pre-analysis

  • Fungal peritonitis (3); tuberculous peritonitis (1); non-compliance with treatment protocol (2)

Definition of peritonitis

  • Abdominal pain and cloudy peritoneal dialysate occurred with or without fever; peritoneal WCC > 100/mm³ with > 50% polymorphs

Definition of cure

  • Complete resolution of symptoms and signs with a negative culture, and no further episodes in the following 28 days

Definition of treatment failure

  • The persistence of signs and symptoms and if total peritoneal WCC count was more than 50% of the pretreatment value after 3 days of antibiotic treatment

Definition of relapse

  • Recurrence with the same micro-organism within 28 days of clearing of the initial peritonitis episode

Completeness of follow-up

  • Eligible/considered for inclusion: 54 episodes in 46 patients

  • Enrolled/randomised: 54

  • Analysed: 48

  • Per cent followed: 88.9%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk6/5454 (11.1%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Cheng 1997

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 28 days after commencement of treatment

Participants
  • Country: Hong Kong

  • Setting: multicentre, teaching hospital, university

  • Inclusion criteria: patients on CAPD who developed peritonitis

  • Number: treatment group (19 episodes); control group (17 episodes)

  • Age, range (years): treatment group (51.5, 26 to 71); control group (51, 36 to 80)

  • Sex (M/F): treatment group (11/7); control group (6/11)

  • Exclusion criteria: known sensitivity to fluoroquinolones; peritonitis secondary to fungi or tuberculous bacteria; relapsing peritonitis

Interventions

Treatment group

  • Oral ofloxacin: 400 mg loading dose then 300 mg/d maintenance dose

  • Total duration of treatment: 10 days

Control group

  • Ofloxacin: 100 mg/L for the first bag then 25 mg/L dialysate in subsequent bags

  • Total duration of treatment: 10 days

Co-interventions

  • Aluminium phosphate binders were stopped in patients receiving pefloxacin orally but not in those receiving the IP drug

Outcomes
  • Treatment failure

  • Relapse of peritonitis

Notes

Exclusions post randomisation but pre-intervention

  • 7/41 patients were excluded because of protocol violation after an interim analysis

Definition of peritonitis

  • Abdominal pain and cloudy peritoneal dialysate occurred with or without fever; peritoneal WCC > 100/mm³ with > 50% polymorphs

Definition of cure

  • Complete resolution of symptoms and signs with a negative culture, and no further episodes in the following 28 days

Definition of treatment failure

  • The persistence of fever, abdominal pain and cloudy peritoneal effluent and if total peritoneal WCC count > 50% of the pretreatment value after 3 days of antibiotic treatment

Definition of relapse

  • Recurrence with the same micro-organism within 28 days of clearing of the initial peritonitis episode

Completeness of follow-up

  • Eligible/considered for inclusion: 41 patients

  • Enrolled/randomised: 34 patients (36 peritonitis episodes)

  • Analysed: 33 patients (35 peritonitis episodes)

  • Per cent followed: 94.3%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNot described
Incomplete outcome data (attrition bias)
All outcomes
High risk8/36 (22.2%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskEarly termination of study

Cheng 1998

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 28 days from clearing of effluent

Participants
  • Country: Hong Kong

  • Setting: multicentre, teaching hospital

  • Inclusion criteria: patients on CAPD who developed peritonitis

  • Number: treatment group (47); control group (54)

  • Mean age ± SD (years): treatment group (56.5 ± 13.2); control group (56.6 ± 11.0)

  • Sex (M/F): treatment group (25/22); control group (29/25)

  • Exclusion criteria: severe peritonitis with evidence of septicaemia (i.e. high fever and hypotension); peritonitis secondary to tunnel infection; peritonitis secondary to fungi or tuberculous bacteria; relapsing peritonitis; known sensitivity to study medications

Interventions

Treatment group

  • Oral levofloxacin: 300 mg/d

    • Total duration of treatment: 10 days

  • Vancomycin: 1 g (if < 50 kg) or 2 g (body weight > 50 kg) day 1 and day 7

Control group

  • Netromycin: 20 mg/L IP loading dose then 20 mg/L in the first exchange of each day

    • Total duration of treatment: 10 days

  • Vancomycin: 1 g (if < 50 kg) or 2 g (body weight > 50 kg) day 1 and day 7

Outcomes
  • Treatment failure

  • Relapse

Notes

Definition of peritonitis

  • Abdominal pain and cloudy peritoneal dialysate occurred with or without fever; peritoneal WCC > 100/mm³ with > 50% polymorphs

Definition of cure

  • Complete resolution of symptoms and signs with a negative culture, and no further episodes in the following 28 days

Definition of treatment failure

  • The persistence of fever, abdominal pain and cloudy peritoneal effluent and if total peritoneal WCC > 50% of the pretreatment value after 3 days of antibiotic treatment

Definition of relapse

  • Recurrence with the same micro-organism within 28 days of clearing of the initial peritonitis episode

Completeness of follow-up

  • Eligible/considered for inclusion: 113

  • Enrolled/randomised: 101

  • Analysed: 100

  • Per cent followed: 99%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "Randomization was by random selection of sealed envelopes"
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk1/101 patients (1%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Choy 2001

Methods
  • Study design: RCT

  • Time frame: 14 days

Participants
  • Country: Hong Kong

  • Setting: single centre

  • Inclusion criteria: patients with CAPD peritonitis

  • Number: 147 patients (184 episodes); treatment group (93 episodes); control group (91 episodes)

  • Mean age ± SD (years): treatment group (66.5 ± 1.3); control group (63.9 ± 1.4)

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • Intermittent regime: cefazolin (1.5 mg/2 L) + tobramycin (40 mg/2 L) dialysate in one exchange/d

Control group

  • Continuous regime: loading doses of cefazolin (2 mg/2 L) + tobramycin (16 mg/2 L) followed by cefazolin (12.5 mg/L) + tobramycin (6 mg/L) dialysate for every exchange

Co-interventions: NS

Outcomes
  • Primary treatment failure

  • Catheter removal

Notes

Primary treatment failure

  • Reported as primary treatment cure

Catheter removal

  • 10 patients from each group required Tenchoff catheter removal (fungal (7); Pseudomonas (9); E. coli (2); mixed gram negative (1); Staphylococcus (1))

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskUnblinded comparison
Blinding of outcome assessment (detection bias)
All outcomes
High riskUnblinded comparison
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskAbstract only publication

Coban 2004

Methods
  • Study design: parallel quasi-RCT

  • Time frame: NS

Participants
  • Country: Turkey

  • Setting: university hospital

  • Inclusion criteria: CAPD-associated peritonitis; positive dialysate culture with an organism sensitive to the study antibiotics

  • Number: treatment group (12); control group (12)

  • Mean age ± SD (years): treatment group (52.6 ± 5.9); control group (53.2 ± 7.6)

  • Sex (M/F): treatment group (6/6); control group (7/5)

  • Exclusion criteria: completion of antibiotic therapy with 28 days; active exit site infection, tunnel infection; peritonitis attributed to other surgical causes suspected on clinical grounds; presence of peritonitis attributed to fungal or mycobacterial infection

Interventions

Treatment group

  • 2 mL (320 mg) IP IgG with each exchange

  • Antibiotics as for control group

Control group

  • IP ampicillin/sulbactam: 1 g 3 times/d

  • IP netilmicin: 150 mg loading dose; 50 mg/d (added to night exchange)

Outcomes
  • Time for dialysate WCC < 100/mL

  • Time to pain free exchange

  • Relapse

Notes

Definition of peritonitis

  • Two of the following: dialysate WCC > 100/mm³ with more than 50% polymorphs; peritoneal inflammation symptoms; positive dialysate gram stain and subsequent positive culture

Completeness of follow-up

  • Eligible/considered for inclusion: 24

  • Enrolled/randomised: 24

  • Analysed: 24

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskConsecutive allocation to each study arm
Allocation concealment (selection bias)High riskConsecutive allocation to each study arm
Blinding of participants and personnel (performance bias)
All outcomes
High riskNo placebo for IgG used in control arm
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

de Fijter 2001

Methods
  • Study design: parallel RCT

  • Time frame: October 1996 to Octobe1999

  • Follow-up period: 28 days from completion of therapy

Participants
  • Country: The Netherlands

  • Setting: multicentre, teaching hospital, university

  • Inclusion criteria: receiving CAPD; > 18 years

  • Number: treatment group (44); control group (54)

  • Age, range (years): treatment group (61.2, 28 to 76); control group (56.9, 22 to 76)

  • Sex (M/F): treatment group (26/18); control group (24/30)

  • Exclusion criteria: pregnancy; lactating females or those using inadequate contraception; underlying rapidly fatal disease (life expectancy < 2 months post-enrolment); use of any concomitant systemic antimicrobial drug within 1 week prior to enrolment; chronic liver disease (SGOT and/ or SGPT repeatedly 3 times over the upper normal limit); evidence or history of hypersensitivity or other contraindications to quinolones, cephalosporins or rifampicin; prior entry into the present study

Interventions

Treatment group

  • Ciprofloxacin: 50 mg/L added to all exchanges

  • Rifampicin: 50 mg/L added to all exchanges

  • Ciprofloxacin or cephradine stopped when appropriate following culture results

  • Treatment duration: 14 days

Control group

  • Cephradine: 250 mg/L added to all exchanges

  • Treatment duration: 14 days

Co-interventions: NS

Outcomes
  • Treatment failure

  • Bacteriological response

  • Relapse

  • Catheter removal

  • Side effects of treatment

Notes

Definition of peritonitis

  • Dialysate WCC > 100/mm³ with > 50% polymorphs, with or without clinical symptoms and signs of peritonitis or a positive culture

Definition of cure

  • Disappearance of all signs and symptoms related to the infection by day 4 and continued through to day 42

Definition of treatment failure

  • Insufficient lessening of symptoms and signs to qualify as improvement

  • Ongoing symptoms and signs beyond day 4

  • Dialysate WWC > 100/mm³ at day 14

  • Death secondary to uncontrolled infection

  • Catheter removal

Definition of relapse

  • Recurrence with the same organism within 28 days

Completeness of follow-up

  • Eligible/considered for inclusion: 367

  • Enrolled/randomised: 367

  • Analysed: 98

  • Per cent followed: 26.7%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from Methods section of paper: "Treatment was not blinded to patients or clinicians."
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk5/98 (5.1%) lost to follow-up
Selective reporting (reporting bias)Low riskAll important clinical outcomes reported
Other biasUnclear riskNone apparent

Drinovec 1988

Methods
  • Study design: RCT

  • Time frame: NS

Participants
  • Country: Yugoslavia

  • Setting: NS

  • Inclusion criteria: patients who were being treated with CAPD that developed peritonitis with Staphylococcus

  • Number:20 (54 episodes)

  • Age range: 25 to 73 years

  • Sex (M/F): 9/11

  • Exclusion criteria: none

Interventions

Patients with mild forms of peritonitis were administered one combination of two antibiotics: gentamicin + methicillin or gentamicin + cloxacillin or clindamycin + mezlocillin IP

Comparison 1

  • Treatment: gentamicin + methicillin

  • Control: clindamycin + mezlocillin

Comparison 2

  • Treatment: gentamicin + methicillin

  • Control: gentamicin + cloxacillin

Comparison 3

  • Treatment: gentamicin + cloxacillin

  • Control: clindamycin + mezlocillin

Outcomes
  • Treatment failure

  • Complete cure

  • Adverse effects

Notes

Definition of peritonitis

  • Peritonitis was diagnosed when any of two following criteria were present: abdominal pain or soreness, cloudy peritoneal effluent containing WCC ≥ 100/mm³ and micro-organisms in the peritoneal effluent

Adverse effects

  • A reversible toxic effect on the nervus vestibularis was observed in 2 patients receiving gentamicin

Completeness of follow-up

  • 20 patients developed 54 episodes of peritonitis over a 258 month period

  • Results for only 31 peritonitis episodes provided

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskOpen study
Blinding of outcome assessment (detection bias)
All outcomes
High riskOpen study
Incomplete outcome data (attrition bias)
All outcomes
High risk23/54 episodes (43%) were lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Ejlersen 1991

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 1 month after cessation of antibiotic treatment

Participants
  • Country: Denmark

  • Setting: multicentre, teaching hospital, university

  • Inclusion criteria: patients on CAPD who developed peritonitis

  • Number: treatment group (18); control group (18)

  • Mean age ± SD (years): NS

  • Sex (M/F):NS

  • Exclusion criteria: patients previously enrolled in the study; profound hypotension and shock; clinical exit site and/ or tunnel infection; poor treatment compliance

Interventions

Treatment group

  • Initial 24 hours of peritoneal lavage (2 L exchanges, no dwell time) with 60 L dialysis fluid containing vancomycin 20 mg/L and netilmicin 10 mg/L; followed by resumption of usual CAPD regimen and 9 days of IP antibiotics in the same concentration (total 10 days of antibiotic treatment)

Control group

  • Initial 2 rapid exchanges followed by routine CAPD schedule

  • Vancomycin 40 mg/L and netilmicin 10 mg/L added to the initial 2 rapid exchanged, followed by ongoing vancomycin 20 mg/L and netilmicin 10 mg/L for a total of 10 days of antibiotic therapy

Outcomes
  • Time to resolution of peritonitis

  • Treatment failure

  • Relapse

  • Side effects of treatment

Notes

Definition of peritonitis

  • 2/5 possible criteria present: positive Leukostix; cloudy dialysis effluent; abdominal pain; dialysate WCC > 100/µL and > 50% neutrophils; positive culture from dialysis effluent

Definition of cure

  • Normalisation of WCC in the dialysate effluent

Definition of relapse

  • Recrudescence of peritonitis signs and symptoms while still under antibiotic treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 39

  • Enrolled/randomised: 39

  • Analysed: 36

  • Per cent followed: 92.3%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from Results section of paper: "This study was designed as a ...randomized open trial."
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Flanigan 1991

Methods
  • Study design: parallel quasi-RCT

  • Time frame: January 1981 to December 1986

  • Follow-up period: 14 days after completion of treatment

Participants
  • Country: USA

  • Setting: teaching hospital

  • Inclusion criteria: receiving CAPD or CCPD

  • Number: treatment group (83, 181 episodes); control group (48, 82 episodes)

  • Mean age ± SEM (years): treatment group (42.75 ± 2.10); control group (47.12 ± 2.63)

  • Male: treatment group (46%); control group (51%)

  • Exclusion criteria: allergy to both study drugs

Interventions

Treatment group

  • Cephazolin: 50 mg/L of dialysate IP

  • Total duration of treatment: 14 days

Control group

  • Vancomycin: 25 mg/L of dialysate IP

  • Total duration of treatment: 14 days

Co-interventions

  • 2 rapid exchanges at the time of initiation of treatment followed by resumption of the normal dialysis regimen

  • IP heparin 250 U/L

Outcomes
  • Treatment failure

  • Relapse of peritonitis

  • Catheter removal

Notes

Definition of peritonitis

  • Effluent WCC > 100/ µL and > 50% neutrophils

Definition of cure

  • Elimination of all symptoms and signs of infection by the initial 14 days of antibiotics, and remaining infection free for another 14 days following completion of antibiotic therapy

Definition of relapse

  • Recurrence within 14 days of antibiotic treatment of infection with the same organism or with no growth

Completeness of follow-up

  • Eligible/considered for inclusion: 131

  • Enrolled/randomised: 131

  • Analysed: 95 patients (263 episodes of peritonitis)

  • Per cent followed: 72.5%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote from Methods section of paper: "...letters of the alphabet were alternately placed into one of two groups..." with cephazolin and vancomycin each represented by one group
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "...patients were enrolled into treatment groups based upon the first letter of their last name."
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Friedland 1990

Methods
  • Country: UK

  • Study design: parallel RCT

  • Follow-up period: 28 days

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: patients with CAPD-associated peritonitis

  • Number: treatment group (20); control group (20)

  • Age range: treatment group (47 to 79 years); control group (22 to 77 years)

  • Sex (M/F): treatment group (11/9); control group (13/7)

Exclusion criteria: known allergy to any study drug; PD catheter leak; catheter tunnel infection; pregnancy; liver disease; history of convulsions
If any antibiotics had been received in the 48 hours prior to presentation; recurrent peritonitis (any episode within the previous 28 days)

Interventions

Treatment group

  • Ciprofloxacin: 20 mg/L IP with each exchange

  • Total duration of treatment: 10 days

Control group

  • Vancomycin: 12.5 mg/L IP with each exchange

  • Gentamicin: 4 mg/L to alternate exchanges

  • Total duration of treatment: 10 days

Outcomes
  • Treatment failure

  • Relapse of peritonitis

  • Catheter removal

  • Technique failure

  • Side effects of treatment

Notes

Definition of cure

  • No further episodes of CAPD peritonitis in the following 28 days

Completeness of follow-up

  • Eligible/considered for inclusion: 40

  • Enrolled/randomised: 40

  • Analysed: 40

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "Patients were randomized by selection of a numbered envelope (not previously seen by the attending physicians)..."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different number and dosing frequencies of antibiotics in study arms precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)Low riskAll important clinical outcomes reported
Other biasUnclear riskNone apparent

Gadallah 2000c

Methods
  • Study design: parallel quasi-RCT

  • Time frame: 3 years

  • Follow-up period: 6 months

Participants
  • Country: USA

  • Setting: teaching hospital

  • Inclusion criteria: first episode of PD-associated peritonitis

  • Number: treatment group (40); control group (40)

  • Mean age ± SE (years): treatment group (45.1 ± 12.8); control group (48.2 ± 3.3)

  • Sex (M/F): treatment group (19/21); control group (18/22)

  • Exclusion criteria: exit-site or tunnel infection

Interventions

Treatment group

  • Urokinase: 5000 IU/2.5 mL normal saline, administered intraluminally; 4 hour dwell

  • IP antibiotics

Control group

  • IP antibiotics

Outcomes
  • Duration of peritonitis

  • Severity of symptoms and signs of peritonitis

  • Recurrence of peritonitis

  • Relapse

  • Catheter removal

Notes

Definition of treatment failure

  • Persistent peritonitis without improvement in dialysate WCC after 4 days of treatment with specific antibiotic therapy

Definition of relapse

  • Peritonitis caused by the same organism within 3 months of the initial episode of peritonitis or three episodes of peritonitis due to the same organism within a 6 month period

Completeness of follow-up

  • Eligible/considered for inclusion: 80

  • Enrolled/randomised: 80

  • Analysed: 80

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote from Methods section of paper: "...randomization was based on consecutive case approach..."
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "...randomization was based on consecutive case approach..."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: no mention of use of placebo in control group
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Gucek 1994

Methods
  • Study design: parallel RCT

  • Time frame: November 1991 to June 1993

  • Follow-up period: NS

Participants
  • Country: Slovenia

  • Setting: teaching hospital

  • Inclusion criteria: adults receiving CAPD therapy who developed peritonitis

  • Number: 23

  • Mean age ± SD: 53.5 ± 11 years

  • Sex (M/F): 15/8

  • Exclusion criteria: NS

Interventions

Treatment group

  • Oral ofloxacin: 300 mg loading dose then 200 mg/d for an average of 10 days

Control group

  • Cephazolin: 100 mg IP loading dose then 250 mg IP/exchange for 10 days

Outcomes
  • Treatment failure

Notes

Definition of peritonitis

  • 2/3 criteria: abdominal discomfort and pain; cloudy peritoneal effluent with WCC > 100/mm³; positive microbiological findings of the effluent

Completeness of follow-up

  • Eligible/considered for inclusion: 23

  • Enrolled/randomised: 23

  • Analysed: 23

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Gucek 1997

Methods
  • Study design: parallel RCT

  • Time frame: November 1993 to September 1996

  • Follow-up period: NS

Participants
  • Country: Slovenia

  • Setting: university

  • Inclusion criteria: CAPD-associated peritonitis

  • Number: 34 (52 episodes)

  • Mean age ± SD: 57.2 ± 13.6 years

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • Cephazolin: 500 mg IP loading dose then 250 mg/exchange maintenance dose

  • Netilmicin: 80 mg to 120 mg IP loading dose then 40 mg IP daily maintenance dose

Control group

  • Vancomycin: 2 g IP every 5 to 7 days

  • Ceftazidime: 1 g IP loading dose then 250 mg IP/exchange maintenance dose

Outcomes
  • Treatment failure

Notes

Definition of peritonitis

  • 2/3 criteria: abdominal discomfort and pain; cloudy peritoneal effluent with WCC > 100/mm³; positive microbiological findings of the effluent

Definition of treatment failure

  • Failure to show considerable clinical improvement within 2-5 days of initial antibiotic treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 34 patients (52 episodes)

  • Enrolled/randomised: 34 patients (52 episodes)

  • Analysed: 34 patients (52 episodes)

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different frequencies of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Hernandez 2004

Methods
  • Study design: quasi-RCT

  • Time Frame: NS

  • Follow-up period: NS

Participants
  • Country: Mexico

  • Setting: single centre

  • Inclusion criteria: patients who had clinical data of peritonitis associated with CAPD were randomly selected from the CAPD Program of the nephrology service of Hospital Regional

  • Number: treatment group (20); control group (20)

  • Age (years): treatment group (53.3); control group (52.8)

  • Sex (M/F): treatment group (11/9); control group (15/5)

  • Exclusion criteria: unclear

Interventions

Treatment group

  • Cefepime IP: 500 mg/dL at onset, and afterwards at 125 mg/dL, in dialysis solution at 1.5%, refilled 4 times/d for 10 days

Control group

  • Cefotaxim-amikacin IP: at the onset, cefotaxime was administered at doses of 250 mg/L, with amikacin at 25 mg/dL, in dialysis solution at 1.5%, refilled 4 times/d for 10 days

Co-interventions

  • At 48 and 96 hours, control was taken of the cytochemistry of the initial dialysis fluid, of the culture and of gram-stain. Addition of another antimicrobial in the case of identification of fungi, mycobacteria, or bacteroides

Outcomes
  • Complete cure

Notes

Definition of cure

  • Normal leukocyte count in cytochemical of the dialysis liquid, as well as remission of clinical signs and symptoms

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskUnblinded comparison
Blinding of outcome assessment (detection bias)
All outcomes
High riskUnblinded comparison
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskNot described
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskPossible translation errors

Innes 1994

Methods
  • Setting/ design: parallel RCT

  • Time frame: NS

  • Follow-up period: 6 months

Participants
  • Country: UK

  • Setting: single centre

  • Inclusion criteria: resistant PD-associated peritonitis (no resolution of peritonitis within 4 days of appropriate antibiotic therapy) or recurrent peritonitis (a third episode of peritonitis with the same organism within 6 months despite appropriate antibiotic therapy)

  • Number: treatment group (12); control group (12)

  • Age: median 57 years (range 32 to 76 years)

  • Sex (M/F): 14/10

  • Exclusion criteria: fungal peritonitis; culture negative peritonitis; tunnel or exit site infection

Interventions

Treatment group

  • 5000 Plough Units of urokinase/5 mL of normal saline, administered via IP route; 2 hour dwell

  • 14 days of antibiotics (determined by causative organism)

Control group

  • Placebo (5 mL normal saline)

  • 14 days of antibiotics (determined by causative organism)

Outcomes
  • Treatment failure

Notes

Definition of peritonitis

  • 2/3 criteria: dialysate WCC > 100 mm³; positive dialysate culture; abdominal pain

Definition of cure

  • Disappearance of symptoms and signs related to infection and a decrease in the dialysate WCC < 100/mm³ for 4 weeks after therapy

Definition of treatment failure

  • No clinical improvement, or modification of therapy due to clinical deterioration, or catheter removal

Completeness of follow-up

  • Eligible/considered for inclusion: 73

  • Enrolled/randomised: 73

  • Analysed: 65

  • Per cent followed: 89.0%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low risk

Quote from paper: "Double-blind clinical trial"

Comment: placebo used in control arm

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Jiménez 1996

Methods
  • Study design: RCT

Participants
  • Country: Spain

  • Setting: NS

  • Inclusion criteria: NS

  • Number: 24 (67 episodes)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: unclear

Interventions

Treatment group

  • Vancomycin and cefotaxime

Control group

  • Vancomycin and tobramycin

Outcomes
  • Treatment failure

  • Recurrence of peritonitis

  • Catheter removal

Notes

Definition of treatment success

  • Resolution of peritonitis within 4 days of urokinase or placebo in the case of persistent infection, or no recurrence with the same organism within 6 months for recurrent infection

Completeness of follow-up

  • Eligible/considered for inclusion: 24

  • Enrolled/randomised: 24

  • Analysed: 24

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskPublished in abstract form only; possible translation errors

Khairullah 2002

Methods
  • Study design: parallel RCT

  • Time frame: 1 October 1997 to 20 September 1999

Participants
  • Country: USA

  • Setting: teaching hospital

  • Inclusion criteria: PD-associated peritonitis

  • Number: 30 (51 episodes)

  • Mean age (range): 48 years (26 to 74)

  • Sex (M/F): 17/13

  • Exclusion criteria: sensitivities to penicillin or vancomycin; already receiving antibiotics; known to be noncompliant; could not follow instructions; < 18 years; pregnancy

Interventions

Treatment group

  • Cephazolin: 1 g IP loading dose then 125 mg/L with each exchange for 2 to 3 weeks according to culture results

Control group

  • Vancomycin: 1 g/L IP loading dose, repeated at day 5 or day 8 according to residual kidney function, for 2 weeks

Co-interventions

  • Gentamicin: 40 mg/d IP added to one exchange (both groups)

Outcomes
  • Treatment failure

  • Relapse

  • Catheter removal

Notes

Definition of peritonitis

  • Effluent WCC > 100/mm³ with > 50% neutrophils

Definition of cure

  • Elimination of all signs and symptoms of peritonitis by the prescribed duration of treatment; infection free for 2 weeks after cessation of treatment

Definition of relapse

  • Infection with the same micro-organism within 2 weeks of treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 91 patients

  • Enrolled/randomised: 91 patients

  • Analysed: 30 patients (51 episodes)

  • Per cent followed: 82.4%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "Patients were... randomised by the (dialysis) nurse.."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different dosing regimens between study arms precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk9/51 (17.6%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Klaus 1995a

Methods
  • Study design: parallel RCT

  • Time frame: June 1993 to January 1997

  • Follow-up period: median 19 months (range 1 to 44)

Participants
  • Country: Germany

  • Setting: multicentre; 13 mid-European paediatric dialysis centres

  • Inclusion criteria: children and adolescents; CAPD therapy; > 4 weeks without peritonitis, exit site infections or other infections treated with antibiotics in prevalent CPD patients

  • Number: treatment group 1 (40); treatment group 2 (41); control group 1 (40); control group 2 (43)

  • Median age (range): 11.4 years (0.7 to 21.8)

  • Sex (M/F): NS

  • Exclusion criteria: patients receiving continuous local or systemic antibiotics

Interventions

Treatment group 1

  • Teicoplanin: 7.5 mg/kg body weight loading dose then 20 mg/L dialysate added to each dialysate exchange

  • Ceftazidime: 250 mg/L dialysate loading dose then 125 mg/L added to each dialysate exchange

Treatment group 2

  • Teicoplanin: 15 mg/kg loading dose day 1 and day 7

  • Ceftazidime: 500 mg/L dialysate loading dose then 250 mg/L once daily added to long (9 to 12 hour) dwell

Control group 1

  • Vancomycin: 15 mg/kg body weight loading dose then 30 mg/L dialysate added to each dialysate exchange

  • Ceftazidime: 250 mg/L dialysate loading dose then 125 mg/L added to each dialysate exchange

Control group 2

  • Vancomycin: 30 mg/kg body weight day 1 and day 7

  • Ceftazidime: 500 mg/L dialysate loading dose then 250 mg/L once daily added to long (9 to 12 hour) dwell

Co-interventions

  • Heparin 200 IU/L IP until the dialysate completely cleared

Outcomes
  • Treatment failure

  • Relapse

  • Side effects of treatment

  • Loss of residual kidney function

Notes

Exclusions post randomisation but pre-intervention

  • 2 patients

Definition of peritonitis

  • Dialysate WCC > 100/µL with > 50% polymorphonuclear neutrophils

Definition of cure

  • A decrease in the disease severity score (DSS) by 2 or, if less than 2 initially, when the dialysate WCC had decreased by 50% or more

Definition of treatment failure

  • Deterioration of clinical status after 60 h (increase in the DSS)

Definition of relapse

  • Recurrence of peritonitis with the same organism within 4 weeks after termination of antibiotic treatment

Additional data requested from authors

  • Outcomes based on modality of PD

Completeness of follow-up

  • Eligible/considered for inclusion: 152 patients

  • Enrolled/randomised: 90 (195 episodes)

  • Analysed: 195

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Low riskPerformed locally with a blocking factor of 4
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different antibiotic dosing intervals between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
High risk98/152 (64.5%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Leung 2004

Methods
  • Study design: parallel quasi-RCT

  • Time frame: March 2001 to February 2002

  • Follow-up period: 120 days

Participants
  • Country: Hong Kong

  • Setting: single centre; university teaching hospital

  • Inclusion criteria: PD-associated peritonitis

  • Number: treatment group (51); control group (51)

  • Mean age ± SD (years): treatment group (61.0 ± 12.2); control group (57.1 ± 12.2)

  • Sex (M/F): treatment group (26/25); control group (25/26)

  • Exclusion criteria: recurrent peritonitis within 30 days prior to presentation, concomitant antibiotics for other indications, catheter leak or malfunction, and known allergy to imipenem / cilastatin, ceftazidime, or cefazolin

Interventions

Treatment group

  • Iimipenem/cilastin IP: loading dose 500 mg (6 hour dwell) then maintenance dose 100 mg/2 L dialysate bag 4 times/d

Control group

  • Cephazolin IP: loading dose 1 g (6 hour dwell) then maintenance dose 250 mg/2 L dialysate bag 4 times/d

  • Ceftazidime IP loading dose 1 g (6 hour dwell) then maintenance dose 250 mg/ 2 L dialysate bag 4 times/d

Co-interventions

  • Three rapid hourly dialysis cycles at presentation

  • Heparin sodium 1000 U IP/2 L dialysis solution until dialysate cleared

  • Oral nystatin for fungal prophylaxis until antibiotic therapy completed

  • Oral rifampicin added for S. aureus infections and IP netilmicin for Pseudomonas infections, and treatment continued for at least 21 days in these cases

Outcomes
  • Primary response

  • Complete cure

  • Catheter removal

Notes

Definition of peritonitis

  • Two of abdominal pain, cloudy dialysate or peritoneal effluent WCC > 100/mm³ with > 50% neutrophils and positive gram stain or culture

Definition of primary response

  • Resolution of abdominal pain, clearing of dialysate and dialysate neutrophil count < 100/µL on day 10

Definition of relapse

  • Recurrence of peritonitis by the same organism within 28 days of completion of a course of antibiotics

Complete cure

  • Complete cure of peritonitis by antibiotics alone, without relapse within 120 days

Completeness of follow-up

  • Eligible/considered for inclusion: 102

  • Enrolled/randomised: 102

  • Analysed: 102

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "...patients were randomized according to their date of presentation."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: differences in the number of antibiotics administered in study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo
Incomplete outcome data (attrition bias)
All outcomes
Low risk1/102 (1%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Lui 2005

Methods
  • Study design: parallel RCT

  • Time frame: October 2002 to October 2004

  • Follow-up period: 42 days

Participants
  • Country: Hong Kong

  • Setting: single centre, university teaching hospital

  • Inclusion criteria: CAPD patients 18 years of age or older with clinical evidence of peritonitis

  • Number: treatment group (51); control group (51)

  • Mean age ± SD (years): treatment group (66.7 ± 12.2); control group (63.7 ± 14.6)

  • Sex (M:F): treatment group (1:1); control group (1.3:1)

  • Exclusion criteria: known hypersensitivity to cephalosporins or amino glycosides; suspected fungal or tuberculous peritonitis; relapsing peritonitis; active exit site infection

Interventions

Treatment group

  • Ceftazidime: 1 g/2 L dialysate bag IP daily

Control group

  • Netilmicin: 0.6 mg/kg body weight/2 L dialysate bag IP daily

Co-interventions

  • Cephazolin 1 g/2 L dialysate bag IP daily

  • Antibiotics changed if there was a failure to respond to assigned antibiotics by day 3; antibiotics either adjusted according to culture results or changed to second line antibiotics (vancomycin and amikacin) if cultures were negative

Outcomes
  • Primary treatment failure

  • Secondary treatment failure

  • Relapse of peritonitis

  • Catheter removal

  • Decline in residual kidney function

Notes

Definition of peritonitis

  • Abdominal pain and cloudy dialysate, and a dialysate WCC > 100 mm³ with > 50% neutrophils

Definition of primary cure

  • A complete resolution of signs and symptoms of peritonitis with a negative dialysate culture and no further episodes of peritonitis within 28 days following the cessation of antibiotic treatment

Definition of primary treatment failure

  • The presence of fever, abdominal pain and turbid peritoneal dialysate, and if the total peritoneal WCC is > 50% of pretreatment values after 3 days of treatment by the assigned antibiotics

Definition of secondary treatment failure

  • Treatment failure despite adjustment of antibiotics or changing to second line antibiotics

Definition of relapse

  • Recurrence of peritonitis with the same micro-organism within 28 days of clearing of the initial antibiotic episode and cessation of antibiotic therapy

Completeness of follow-up

  • Eligible/considered for inclusion: 112

  • Enrolled/randomised: 104

  • Analysed: 102

  • Per cent followed: 98%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "...randomization was done by computer generated randomization tables."
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "...randomization was done by computer generated randomization tables."
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from Methods section of paper: "This was a...open-labeled study..."
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk2/102 (2%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Lupo 1997

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 4 weeks after completion of therapy

Participants
  • Country: Italy

  • Setting: multicentre, university

  • Inclusion criteria: CAPD-associated peritonitis

  • Number: treatment group (39); control group (34)

  • Mean age ± SD (years): treatment group (66.7 ± 12); control group (66.9 ± 13)

  • Sex (M/F): treatment group (23/16); control group (13/16)

  • Exclusion criteria: known or suspected sensitivity to the study drug(s); peritonitis caused by tunnel infection; effective antibiotic therapy in the previous 48 hours

Interventions

Treatment group

  • Teicoplanin: 400 mg IV loading dose then 40 mg IP added to each exchange

Control group

  • Cephalothin: 2 g IV then 500 mg IP added to each exchange

Co-interventions

  • Tobramycin 120 mg IM loading dose then 10 mg IP added to each exchange (both groups)

  • In both groups IP antibiotics were given with each exchange in the first week of treatment, in alternate bags in the second week, and in an overnight bag in the third week

Outcomes
  • Treatment failure

  • Microbiological eradication

  • Relapse

  • Side effects of treatment

Notes

Definition of peritonitis

  • 2/3 criteria: dialysate WCC > 100/mm³; positive dialysate culture; abdominal pain

Definition of cure

  • Disappearance of symptoms and signs related to infection and a decrease in the dialysate WCC < 100/mm³ for 4 weeks after therapy

Definition of treatment failure

  • No clinical improvement, or modification of therapy due to clinical deterioration, or catheter removal

Completeness of follow-up

  • Eligible/considered for inclusion: 73

  • Enrolled/randomised: 73

  • Analysed: 65

  • Per cent followed: 89.0%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Unclear riskNo information provided
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk8/73 (11.0%) lost to follow-up
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Lye 1993

Methods
  • Study design: parallel RCT

  • Time frame: 1 January to 31 December 1991

  • Follow-up period: 14 days after completion of treatment

Participants
  • Country: Singapore

  • Setting: teaching hospital

  • Inclusion criteria: CAPD-associated peritonitis

  • Number: treatment group (33); control group (30)

  • Mean age ± SEM (years): treatment group (61.6 ± 8.5); control group (59.0 ± 12.0)

  • Sex (M/F): treatment group (11/19); control group (9/21)

  • Exclusion criteria: history of allergy to the antibiotics; chronic exit-site or tunnel infection

Interventions

Treatment group

  • Oral pefloxacin: 400 mg twice daily

Control group

  • Gentamicin: 80 mg IP loading dose then 15 mg/2 L dialysate bag

Co-interventions

  • Single dose vancomycin 1 g IP (both groups)

  • Total duration of antibiotic therapy 14 days

  • Antibiotics changed after 72 hours according to culture results

Outcomes
  • Treatment failure

  • Relapse

  • Catheter removal

  • Side effects of treatment

Notes

Definition of peritonitis

  • Cloudy peritoneal effluent; dialysate WWC > 100/mL with > 50% polymorphonuclear neutrophils

Definition of cure

  • Resolution of symptoms and signs of peritonitis; clearing of peritoneal fluid; negative bacterial culture

Definition of treatment failure

  • Persistence of cloudy dialysis effluent after 72 hours of appropriate antibiotic treatment

Definition of relapse

  • Peritonitis with the same pathogen or a negative culture within 14 days after completion of treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 60

  • Enrolled/randomised: 60

  • Analysed: 60

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)Low riskAll clinically relevant outcomes reported
Other biasUnclear riskNone apparent

Lye 1995

Methods
  • Study design: parallel quasi-RCT

  • Time frame: NS

  • Follow-up period:14 days following completion of antibiotic treatment

Participants
  • Country: Singapore

  • Setting: teaching hospital, university

  • Inclusion criteria: new episode of CAPD peritonitis

  • Number: treatment group (37); control group (36)

  • Mean age ± SD (years): treatment group (59.6 ± 13.1); control group (56.6 ± 11.7)

  • Sex (M/F): treatment group (16/12); control group (14/22)

  • Exclusion criteria: NS

Interventions

Treatment group

  • Gentamicin: 40 mg IP/d

Control group

  • Gentamicin: 10 mg/2 L dialysate IP 4 times/d

Co-interventions

  • Vancomycin 1 g

  • Antibiotics modified after 72 hours according to culture results

  • Total of 14 days of antibiotic therapy

Outcomes
  • Treatment failure

  • Relapse

Notes

Definition of peritonitis

  • Cloudy peritoneal effluent; dialysate WCC > 100/mL with > 50% polymorphonuclear neutrophils

Definition of cure

  • Resolution of symptoms and signs of peritonitis; clearing of peritoneal fluid; negative bacterial culture

Definition of treatment failure

  • Persistence of infection despite adequate antibiotic treatment

Definition of relapse

  • Infection occurring within 14 days of stopping treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 100 episodes

  • Enrolled/randomised: 100

  • Analysed: 100

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskQuote from Methods section of paper: "Patients were alternately assigned to" study
Allocation concealment (selection bias)High riskQuote from Methods section of paper: "Patients were alternately assigned to" study
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different antibiotic dosing intervals between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Merchant 1992

Methods
  • Country: UK

  • Study design: parallel RCT

  • Follow-up period: 14 days

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: CAPD-associated peritonitis

  • Number: treatment group (30); control group (30)

  • Mean age ± SD (years): treatment group (49.4 ± 3.0); control group (55.0 ± 2.5)

  • Sex (M/F): treatment group (17/13); control group (16/14)

  • Exclusion criteria: peritonitis in the preceding 3 months; previous episode of peritonitis during the study period; suspected of having gram negative peritonitis; an episode of peritonitis within the previous 4 weeks No organisms on gram stain

Interventions

Treatment group

  • Imipenem: 1 g IP to alternate exchanges; changed mid-study to 0.5 g IP to alternate exchanges

Control group

  • Vancomycin: 500 mg IP loading dose then 100 mg/d IP

  • Netilmicin: 100 mg (if > 60 kg) or 60 mg (if < 60 kg) IP loading dose then 50 mg/d (if > 60 kg) or 40 mg/d (if < 60 kg) IP

Antibiotics continued for 5 days beyond total clearing of dialysate and a decrease in the dialysate WCC to < 100/mm³

Outcomes
  • Treatment failure

  • Peritonitis relapse

  • Catheter removal

  • Adverse effects (convulsions)

Notes

Definition of peritonitis

  • Dialysate WCC > 100/mm³ with > 50% polymorphonuclear neutrophils

Definition of cure

  • Clearing of peritoneal fluid; decrease in the dialysate WCC to < 100/mm³

Definition of treatment failure

  • Insufficient lessening of symptoms and signs to qualify as improvement

Definition of relapse

  • Return of peritonitis with the same organism within 14 days of stopping treatment, or no growth for an initially culture negative episode

Completeness of follow-up

  • Eligible/considered for inclusion: 60

  • Enrolled/randomised: 60

  • Analysed: 56

  • Per cent followed: 93.3%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High risk

Quote: "...this open, randomized prospective study"

Comment: different antibiotic dosing frequencies between study groups precludes blinding

Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low risk4/60 (6.7%) lost to follow-up
Selective reporting (reporting bias)Low riskAll clinically significant outcomes reported
Other biasUnclear riskNone apparent

Raman 1985

Methods
  • Study design: quasi-RCT

  • Time frame: 1 September 1982 to 31 August 1983 (12 months)

  • Follow-up period: every patient was reviewed 10 days after starting treatment, i.e. 3 days after stopping antibiotics, to confirm resolution of peritonitis

Participants
  • Country: UK

  • Setting: single centre

  • Inclusion criteria: all patients treated by CAPD in the Wessex Region developing peritonitis

  • Number: treatment group (29); control group (29)

  • Mean age ± SD (years): treatment group (53.3 ± 10); control group (46.2 ± 11.5)

  • Sex (M/F): NS

  • Exclusion criteria: interference with treatment protocol

Interventions

Treatment group

  • Initial IM injection of 750 mg of cefuroxime followed by 375 mg IP added to each CAPD bag for 7 days

Control group

  • Initial IM injection of 500 mg of cephradine followed by oral cephradine 500 mg 4 times/d for 7 days

Co-interventions

  • 4 rapid 2 L lavage cycles within 1 hour while in the hospital

Outcomes
  • Treatment failure

  • Successful treatment/complete cure

Notes

Exclusions post treatment allocation but pre-intervention

  • Peritonitis occurring 5 days within catheter insertion (2); post kidney transplantation (1); septicaemia (1); tunnel abscess (1); recurrent gram negative peritonitis (1); non-compliance (1)

Definition of peritonitis

  • Abdominal pain and cloudy peritoneal dialysate with white blood cells in the CAPD fluid determined by light microscopy

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)High riskAlternate allocation to treatment with either IP cefuroxime or PO cephradine
Allocation concealment (selection bias)High riskInadequate. Treatment was allocated by alternation
Blinding of participants and personnel (performance bias)
All outcomes
High riskUnblinded comparison
Blinding of outcome assessment (detection bias)
All outcomes
High riskUnblinded comparison
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskNo adverse events extractable

Tapson 1990

Methods
  • Study design: parallel RCT

  • Time frame: December 1988 to March 1990

  • Follow-up period: 28 days

Participants
  • Country: UK

  • Setting: single centre

  • Inclusion criteria: CAPD therapy; cloudy dialysate attributed to peritonitis

  • Number: treatment group (25); control group (25)

  • Mean age, range (years): treatment group (58.8, 30 to 76); control group (55.3, 30 to 76)

  • Sex (M/F): NS

  • Exclusion criteria: vomiting; chronic liver disease; history of convulsions; allergy to compounds of the nalidixic acid/ quinolone class; pregnancy; co-existing antibiotic therapy

Interventions

Treatment group

  • Ciprofloxacin: 500 mg (if >70 kg) or 250 mg (if < 70 kg) PO four times/d at the time of each dialysis exchange

Control group

  • Vancomycin: 30 mg/2 L dialysate bag

  • Netilmicin: 30 mg to alternate 2 L dialysate bags

Antibiotics modified after 48 hours if appropriate according to sensitivity results

Co-interventions

  • 3 x 2 L dialysate flush exchanges after the diagnosis of peritonitis was established

Outcomes
  • Treatment failure

  • Microbiological eradication

  • Relapse

  • Nausea

  • Other side effects of treatment

Notes

Definition of peritonitis

  • Dialysate WCC > 100/µL with or without other symptoms and signs

Definition of cure: NS

Definition of treatment failure: NS

Completeness of follow-up

  • Eligible/considered for inclusion: 25

  • Enrolled/randomised: 25

  • Analysed: 25

  • Per cent followed: 25%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Low riskQuote from Methods section of paper: "...patients were randomized using a predetermined randomization code, generated by a computer program, in blocks of ten subjects..."
Allocation concealment (selection bias)Low riskQuote from Methods section of paper: "...patients were randomized using a predetermined randomization code, generated by a computer program, in blocks of ten subjects..."
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different routes of antibiotic administration between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Tong 2005a

Methods
  • Study design: RCT

  • Time frame: March 2000 to July 2003

  • Follow-up period: 28 days

Participants
  • Country: China

  • Setting: single centre

  • Inclusion criteria: resistant PD-associated peritonitis

  • Number: treatment group (44); control group (44)

  • Mean age ± SD (years): treatment group (57.3 ± 13.); control group (58.5 ± 12.8)

  • Sex (M/F): treatment group (23/21); control group (18/26)

  • Exclusion criteria: fungal or mycobacterial peritonitis; surgical cause of acute peritonitis; allergy to urokinase

Interventions

Treatment group

  • Urokinase: 60,000 IU/20 mL normal saline IP, 2 hour dwell period; repeated in 2 days if required

Control group

  • Placebo: 20 mL normal saline

Co-interventions

  • Antibiotics

Outcomes
  • Treatment failure

  • Relapse

  • Catheter removal

  • Death

  • Length of hospitalisation

  • Side effects attributable to urokinase

Notes

Definition of peritonitis

  • 2 of the following: generalised abdominal pain and/ or cloudy dialysate; dialysate WCC > 100/mL and predominant polymorphs; positive gram stain or culture

Definition of cure

  • Disappearance of symptoms and signs and clearing of dialysate

Definition of treatment failure

  • Cessation of PD and initiation of haemodialysis

Completeness of follow-up

  • Eligible/considered for inclusion: 95

  • Enrolled/randomised: 88

  • Analysed: 88

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
Low riskQuote from Methods section of paper: "This study was...a double-blind, randomized, placebo-controlled... trial."
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)Low riskAll clinically significant outcomes reported
Other biasUnclear riskNone apparent

Vargemezis 1989

Methods
  • Study design: RCT

  • Time frame: NS

  • Follow-up period: NS

Participants
  • Country: Greece

  • Setting: single centre

  • Inclusion criteria: patients who presented with probable CAPD-associated gram-positive peritonitis: identification of gram-positive organisms on gram stain, or any two of abdominal pain, a cloudy effluent, or > 100 WBC/mL dialysate

  • Number: 35; treatment group (40 peritonitis episodes); control group (20 peritonitis episodes)

  • Mean age ± SD (years): NS

  • Sex (M/F): 20/15

  • Exclusion criteria: suspected of having gram-negative peritonitis, and episode of peritonitis within the previous 4 weeks, or no organisms on gram stain

Interventions

Treatment group

  • Vancomycin IP: A loading dose of 1 g was administered into the first CAPD exchange followed by 30 mg/L into each CAPD exchange for a 10 days

Control group

  • Vancomycin IV: 2 x 1 g IV doses administered, the first at admission and the second 7 days later

Co-interventions: NS

Outcomes
  • Treatment failure

  • Complete cure

  • Relapse

  • Adverse effects (antibiotic toxicity)

Notes

Definition of peritonitis

  • Identification of gram-positive organisms on gram stain, OR any two of the following: abdominal pain; cloudy effluent; > 100 WBC/mL dialysate

Definition of cure

  • Disappearance of physical symptoms, clearing of dialysate and eradication of the organisms

Adverse effects

  • 2/20 (10%) of patients treated by IV infusion developed allergic reaction with flush and fever at the end of the infusion dose

Definition of relapse

  • Recurrence of peritonitis 2 weeks after administration of the second dose of vancomycin

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNot described
Allocation concealment (selection bias)Unclear riskNot described
Blinding of participants and personnel (performance bias)
All outcomes
High riskUnblinded comparison
Blinding of outcome assessment (detection bias)
All outcomes
High riskUnblinded comparison
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskNot included in meta-analysis

Velasquez-Jones 1995

Methods
  • Study design: parallel quasi-RCT

  • Time frame: NS

  • Follow-up period: NS

Participants
  • Country: Mexico

  • Setting: NS

  • Inclusion criteria: new episode of CAPD-associated peritonitis in paediatric patients

  • Number: treatment group (21); control group (10)

  • Age range: 8 to 17 years

  • Sex (M/F): 11/10

  • Exclusion criteria: NS

Interventions

Treatment group

  • Vancomycin: 30 mg/kg IP for 6 hours day 1 and day 7

Control group

  • Vancomycin: 500 mg/L for 6 hours loading dose then 15 mg/L/exchange for 10 days

Co-interventions

  • Amikacin: 7.5 mg/kg IP for 6 hours then 20 mg/L/exchange for 10 days

Outcomes
  • Treatment failure

  • Relapse

Notes

Definition of peritonitis

  • Abdominal pain; cloudy dialysate; dialysate WCC > 100/mm³, with > 50% polymorphonuclear neutrophils

Definition of cure

  • Resolution of abdominal pain; clearing of dialysate, with < 100/mm³ leukocytes; negative repeat dialysate culture

Definition of treatment failure

  • Ongoing symptoms, particularly abdominal pain; failure of dialysate to clear; dialysate WCC > 50% of that at presentation

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)High riskSequential, non-transparent envelopes
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different antibiotic dosing intervals between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasHigh riskPossible translation errors

Wale 1992

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 6 months

Participants
  • Country: UK

  • Setting: university teaching hospital

  • Inclusion criteria: CAPD therapy; cloudy dialysate attributed to peritonitis

  • Number: treatment group (30); control group (30)

  • Age (years): treatment group (51.3); control group (54.7)

  • Sex (M/F): treatment group (19/11); control group (15/15)

  • Exclusion criteria: < 18 years; allergic to a study medication; pregnant or lactating; received antibiotic therapy in the previous 48 hours; declined to give informed consent

Interventions

Treatment group

  • Cefuroxime: 125 mg/L IP added to each exchange

    • Continued for a minimum of 10 days and 5 days beyond clearing of dialysate

Control group

  • Teicoplanin: 20 mg/L added to each exchange

    • Continued for a minimum of 10 days and 5 days beyond clearing of dialysate

  • Aztreonam: 250 mg/L added to each exchange

    • Continued for a minimum of 10 days and 5 days beyond clearing of dialysate

Antibiotics modified after 48 hours if appropriate according to sensitivity results

Co-interventions

  • IV loading dose of 750 mg cefuroxime (treatment group) or 400 mg teicoplanin plus 2 g aztreonam (control group) if the patient had systemic signs suggestive of bacteraemia

Outcomes
  • Treatment failure

  • Relapse

  • All-cause mortality

Notes

Definition of cure

  • Full recovery equated to complete cure; "Improved" was defined as sufficient recovery to allow discontinuation of antibiotics

Definition of treatment failure

  • Change of antibiotics or tube required

Definition of relapse

  • infection with indistinguishable organism occurring between 1 week and 6 months after end of antibiotic course

Completeness of follow-up

  • Eligible/considered for inclusion: 60

  • Enrolled/randomised: 60

  • Analysed: 60

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different number of antibiotics in treatment regimens between study groups precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear risk7/60 (11.7%) lost to follow-up
Selective reporting (reporting bias)Unclear riskSelective outcome reporting
Other biasUnclear riskNone apparent

Were 1992

Methods
  • Study design: parallel RCT

  • Time frame: 6 months

  • Follow-up period: 14 days after completion of antibiotic therapy

Participants
  • Country: UK

  • Setting: teaching hospital

  • Inclusion criteria: CAPD therapy; peritonitis

  • Number: treatment group (10); control group (10)

  • Mean age ± SD (years): NS

  • Sex (M/F): NS

  • Exclusion criteria: NS

Interventions

Treatment group

  • Cefuroxime: 40 mg/L IP added to each exchange, continued for 5 days beyond clearing of dialysate

Control group

  • Vancomycin: 50 mg IP daily added to alternate bags (1st and 3rd exchanges), continued for 5 days beyond clearing of dialysate

  • Netilmicin: 50 mg (if > 60 kg) or 30 mg (if < 60 kg) IP day 1 then 25 mg (if > 60 kg) or 20 mg (if < 60 kg) IP added to alternate bags (1st and 3rd exchanges), continued for 5 days beyond clearing of dialysate

  • Vancomycin or netilmicin ceased as soon as an organism was isolated and sensitivities available

Co-interventions

  • Heparin 500 µ/L added to the dialysate fluid when indicated

Outcomes
  • Treatment failure

  • Catheter removal

  • Ototoxicity

Notes

Definition of peritonitis

  • Cloudy dialysate effluent; WCC > 100/mm³ and > 50% polymorphonuclear cells

Definition of cure

  • Disappearance of clinical symptoms and signs; dialysate WCC < 100/mm³ for a period of at least 14 days

Definition of treatment failure

  • Persistence of symptoms and signs after 72 hours of treatment, or catheter removal

Definition of relapse

  • Peritonitis with the same organism within 14 days of stopping antibiotics

Completeness of follow-up

  • Eligible/considered for inclusion: 20

  • Enrolled/randomised: 20

  • Analysed: 20

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: different number of antibiotics and dosing intervals between study arms precludes blinding
Blinding of outcome assessment (detection bias)
All outcomes
Low riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Williams 1989

Methods
  • Study design: parallel RCT

  • Time frame: NS

  • Follow-up period: 3 to 12 months

Participants
  • Country: UK

  • Setting: multicentre

  • Inclusion criteria: Adults; CAPD therapy; second recurrence of peritonitis

  • Number: treatment group (17); control group (20)

  • Mean age ± SD (years): treatment group (52.1 ± 4.2); control group (54.1 ± 4.0)

  • Sex (M/F): treatment group (10/7); control group (11/9)

  • Exclusion criteria: NS

Interventions

Treatment group

  • Urokinase injection: 5000 IU/2 mL saline into the Tenckhoff catheter; remained in the catheter for 2 hours; performed on the second and fourth days following recurrence of peritonitis

Control group

  • Catheter removal and replacement usually within 5 days of recurrence of peritonitis

Co-interventions

  • 10 days of appropriate IP antibiotics

Outcomes
  • Treatment failure

  • Recurrence of peritonitis

  • Catheter removal and replacement

  • Side effects of treatment

Notes

Definition of peritonitis

  • Abdominal pain or pyrexia; dialysate WCC > 10⁵/L

Definition of cure

  • Clearing of peritoneal fluid by day 10; clinical improvement

Definition of treatment failure

  • Recurrence of peritonitis (reappearance of peritonitis within 3 weeks of finishing IP antibiotic treatment)

Completeness of follow-up

  • Eligible/considered for inclusion: 37

  • Enrolled/randomised: 37

  • Analysed: 37

  • Per cent followed: 100%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Unclear riskNo information provided
Blinding of participants and personnel (performance bias)
All outcomes
High riskComment: unblinded comparisons
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Low riskAll patients followed
Selective reporting (reporting bias)High riskSelective outcome reporting
Other biasUnclear riskNone apparent

Wong 2001

  1. a

    CAPD - continuous ambulatory peritoneal dialysis; CCPD - continuous cyclic peritoneal dialysis; IP - intraperitoneal; IV - intravenous; NS - not stated; PD - peritoneal dialysis; WCC - white cell count

Methods
  • Study design: parallel RCT

  • Time frame: 1 January 1998 to 30 June 2000

  • Follow-up period: 28 days from completion of antibiotics

Participants
  • Country: Hong Kong

  • Setting: teaching hospital

  • Inclusion criteria: ≥ 18 years; CAPD therapy for > 4 weeks before the onset of peritonitis

  • Number: treatment group (39); control group (34)

  • Mean age ± SD (years): treatment group (58 ± 14); control group (59 ± 10)

  • Sex (M/F): treatment group (23/16); control group (18/16)

  • Exclusion criteria: completion of antibiotic therapy for peritonitis within 28 days; active exit site infection, tunnel infection and/or subcutaneous leakage; signs and symptoms of septicaemia with oral temperature > 38.5°C and/ or systolic blood pressure < 100 mm Hg; known history of hypersensitivity to cefepime, vancomycin or netilmicin; known history of aminoglycoside ototoxicity; current antibiotic therapy for any reason; known history of cirrhosis, diverticulosis, and malignancy; peritonitis attributed to other surgical cause suspected on clinical grounds; inability to administer IP drugs; presence of peritonitis attributed to fungus or mycobacterial infection; pregnancy

Interventions

Treatment group

  • Cefepime: 2 g IP loading dose, 1 g IP daily for 10 days

Control group

  • Vancomycin: 1 g IP day 1 and day 7

    • Vancomycin ceased day 5 if gram negative bacteria isolated

  • Netilmicin: 80 mg IP loading dose, 40 mg IP daily for 10 days

    • Netilmicin ceased day 5 if gram positive bacteria isolated

Co-interventions

  • Antibiotics changed if no clinical improvement; antibiotics continued if clinical improvement, even if isolated bacteria was resistant

Outcomes
  • Treatment failure

  • Relapse

  • Death due to peritonitis

  • Hospitalisation rate

  • Duration of hospitalisation

  • Side effects of treatment

Notes

Exclusions post randomisation but pre-intervention

  • Fungal peritonitis (6); incorrect diagnosis (2)

Definition of peritonitis

  • Signs and symptoms of peritoneal inflammation; dialysate WCC > 100/mL, and > 50% polymorphonuclear cells, and bacteria on gram stain or culture

Definition of cure

  • Clearing of peritoneal fluid by day 10; clinical improvement

Definition of treatment failure

  • Modification of treatment required because of persistence of signs and symptoms of peritonitis at days 5 through to 10; dialysate WCC > 100 on day 10

Definition of relapse

  • Dialysate cleared on day 10 but peritonitis due to the same organism occurred within 28 days of completion of antibiotic treatment

Completeness of follow-up

  • Eligible/considered for inclusion: 81

  • Enrolled/randomised: 81

  • Analysed: 73

  • Per cent followed: 90.1%

Risk of bias
BiasAuthors' judgementSupport for judgement
Random sequence generation (selection bias)Unclear riskNo information provided
Allocation concealment (selection bias)Low riskQuote from paper: "Patients were randomized...by drawing sealed envelopes..."
Blinding of participants and personnel (performance bias)
All outcomes
High riskQuote from paper: "The study is a prospective, open-label...clinical trial."
Blinding of outcome assessment (detection bias)
All outcomes
Unclear riskNo information provided
Incomplete outcome data (attrition bias)
All outcomes
Unclear riskComment: 8 patients were excluded after randomisation, 5 in group A and 3 in group B. 6 exclusions were due to fungal peritonitis, but the distribution between groups A and B is not stated
Selective reporting (reporting bias)Low riskAll clinically significant outcomes reported
Other biasUnclear riskNone apparent

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Al-Wali 1992Results reported according to individual agents used rather than allocated treatment group
Albin 1986Not appropriate population
Artic 1997Not appropriate population
Bannister 1987Not appropriate intervention
Casey 2000Not appropriate population
Cavdar 2004Not appropriate population
Celik 1999Letter, not RCT
Chadwick 1999Retrospective study, not RCT
Chaimovitz 1994Review article, not RCT
Danielsson 1997Not appropriate population
de Fijter 1989Not appropriate population
De Groc 1983Not RCT
Dratwa 1987Not RCT
Dryden 1993Letter, not RCT
Durand 1994Considered peritonitis prevention rather than treatment
Ersoy 1998Not RCT
Fabbri 1982Considered peritonitis prevention rather than treatment
Flanigan 1994Not appropriate population
Goffin 1997Letter, not RCT
Greenbaum 1995Not appropriate outcome
Guest 1996Not RCT
Hancock 1989Letter, not RCT
ISRCTN39675087Not appropriate population
Keller 1984Not appropriate population
Klaus 2002Not appropriate population
Lai 1997Not RCT
Levesque 2003Retrospective study, not RCT
Li 2000Not RCT
McIntosh 1985Not appropriate outcome
Mylotte 1999Not appropriate population
Plum 1997aNot appropriate population
Posthuma 1997Not appropriate population
Qamar 2009Not appropriate intervention
Ranganathan 2010Not appropriate population
Read 1985Retrospective control, not RCT
Restrepo 2010Not appropriate outcome
Sharma 1971Considers peritonitis prevention rather than treatment
Sit 2007Not appropriate population
Stegmayr 1991Not appropriate population
Stein 1995Not appropriate population
Thomae 1982Not appropriate outcome
van der Muelen 1989Not appropriate population
Varghese 2002Not RCT
Wang 1996Considered exit site infections rather than peritonitis
Warady 2003Not appropriate population
Watkins 1998Not appropriate population
Wong 2004bNot appropriate population
Yudis 1995Not RCT
Zacherle 1996Not RCT
Zhang 1993Not RCT

Characteristics of ongoing studies [ordered by study ID]

ISRCTN74962920

Trial name or titleA single centre randomised study to assess the need for performing a line change when a peritoneal dialysis patient presents with peritonitis
MethodsRCT
Participants

Details not provided at time of registration

Target number of participants: 40-50 patients and 40-50 control patients, total 100

InterventionsAntibiotics and no line change compared to antibiotics and a line change
OutcomesPrimary outcome measure(s): To evaluate whether recurrence of peritonitis is more common in patients who present with peritonitis and receive antibiotics and no line change compared to patients who receive antibiotics and a line change
Starting date01/06/2000
Contact information

Ms Patricia Thorn

Renal Unit
Churchill Hospital
Headington

Oxford

UK

Notes 

NCT01785641

Trial name or titleSingle versus combined antibiotic therapy for bacterial peritonitis in continuous ambulatory peritoneal dialysis patients
MethodsParallel RCT
Participants

Inclusion criteria

  • Age ≥ 18 years old

  • ESRD patients on continuous ambulatory peritoneal dialysis more than 4 weeks

  • Presence of symptom or sign of peritonitis

  • Presence of WBC > 100 cell/mm³ with PMN >50% in peritoneal dialysate or gram stain positive for gram positive or gram negative bacteria

Exclusion criteria

  • Presence of polymicrobial organism, non-fermentative gram negative organism, fungus, mycobacteria in peritoneal fluid or culture-negative

  • Peritonitis from the organisms that required combined antibiotic therapy according to ISPD guideline 2010

  • Hospital-acquired peritonitis

  • Presence of catheter-related infection

  • History of peritonitis within 4 weeks

  • Currently taking antibiotic

  • Allergic to the antibiotic that used in the study(penicillin or cephalosporin or quinolone or aminoglycoside)

Interventions

Treatment group 1

  • Ceftazidime+ciprofloxacin

  • 2 synergistic antibiotics: ceftazidime IP + ciprofloxacin orally for gram negative bacterial peritonitis

Control group 1

  • Ceftazidime monotherapy

  • Ceftazidime IP for gram negative bacterial peritonitis

Treatment group 2

  • Cefazolin+gentamicin

  • Cefazolin IP + gentamicin IP for gram positive bacterial peritonitis

Control group 2

  • Cefazolin monotherapy

  • Cefazolin IP for gram positive bacterial peritonitis

OutcomesRelapse or recurrent rate
Starting dateDecember 2012
Contact information

Nalinee Saiprasertkit, MD

Chulalongkorn University

Thailand

Notes 

Ancillary