Antibiotics versus placebo for prevention of postoperative infection after appendicectomy.

  • Review
  • Intervention

Authors


Abstract

Background

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. The cause of appendicitis is unclear and the mechanism of pathogenesis continues to be debated. Despite improved asepsis and surgical techniques, postoperative complications, such as wound infection and intraabdominal abscess, still account for a significant morbidity. Several studies implicate that postoperative infections are reduced by administration of antimicrobial regimes.

Objectives

This review evaluated the use of antibiotics compared to placebo or no treatment in patients undergoing appendectomy. Will these patients benefit from antimicrobial prophylaxis? The outcomes were described according to the nature of the appendix, as either simple appendicitis (including the non-infectious stage) and complicated appendicitis. The efficacy of different antibiotic regimens were not evaluated.

Search methods

We searched The Cochrane Central Register of Controlled Trials (Cochrane Library 2005 issue 1); Pubmed ; EMBASE; and the Cochrane Colorectal Cancer Group Specialised Register (April 2005). In addition, we manually searched the reference lists of the primary identified trials.

Selection criteria

We evaluated Randomised Controlled Trials (RCTs) and Controlled Clinical Trials (CCTs) in which any antibiotic regime were compared to placebo in patients suspected of having appendicitis, and undergoing appendectomy. Both studies on children and adults were reviewed. The outcome measures of the studies were: Wound infection, intra abdominal abscess, length of stay in hospital, and mortality.

Data collection and analysis

Eligibility and trial quality were assessed, recorded and cross-checked by two reviewers.

Main results

Forty-five studies including 9576 patients were included in this review. The overall result is that the use of antibiotics is superior to placebo for preventing wound infection and intraabdominal abscess, with no apparant difference in the nature of the removed appendix. Studies exclusively on children and studies examining topical application reported results in favour to the above, although the results were not significant.

Authors' conclusions

Antibiotic prophylaxis is effective in the prevention of postoperative complications in appendectomised patients, whether the administration is given pre-, peri- or post-operatively, and could be considered for routine in emergency appendectomies.

摘要

背景

抗生素與安慰劑在闌尾切除術後預防感染所扮演的角色

闌尾炎是最常見的腹部急症且需要緊急進行手術。致病原因目前仍不明確,致病機轉仍在討論中。儘管開刀技術已進步許多,但術後併發症,如:傷口感染、腹內膿瘍…等等併發症仍影響很大。部分研究指出在術後給予抗生素,能降低術後感染。

目標

此次的回顧是為了評估闌尾切除術後的病人給予抗生素與安慰劑,或不做任何治療的效果。給予預防性的抗生素是否有較好的預後?最後依據闌尾炎的致病原因(感染或非感染)來做結論。給予不同的抗生素的療效並不在本篇的討論範圍。

搜尋策略

我們搜尋了以下資料庫及臨床試驗: The Cochrane Central Register of Controlled Trials (Cochrane Library 2005 issue 1); Pubmed; EMBASE; and the Cochrane Colorectal Cancer Group Specialised Register (2005四月)。另外,我們再額外搜尋了這些臨床試驗引用之文章。

選擇標準

我們評估了隨機對照試驗(Randomised Controlled Trials, RCTs)及對照臨床試驗(Controlled Clinical Trials, CCTs)中,在疑似闌尾炎及進行闌尾切除術的病人身上給予任何抗生素與安慰劑的比較。這些研究都包括了成人與小孩。研究評估包括傷口感染、腹內膿瘍、住院天數及死亡率。

資料收集與分析

臨床試驗的合適性與品質經由兩位審閱者評估、紀錄以及交叉比對。

主要結論

這次分析包括了45個研究,總共9576個病人。總結全部的研究,不管是闌尾炎的致病原因為何,對於傷口感染與腹內膿瘍的預防,抗生素優於安慰劑。儘管研究結果不顯著,一些小孩研究及外用抗生素的研究結論也是跟之前一樣。

作者結論

使用預防性抗生素對於減少闌尾炎術後併發症,不論是在術前、術中還是術後都是有效的,甚至在緊急闌尾切除手術中,預防性抗生素是可以常規使用。

翻譯人

本摘要由臺北榮民總醫院吳嘉榮翻譯。

此翻譯計畫由臺灣國家衛生研究院(National Health Research Institutes, Taiwan)統籌。

總結

預防性抗生素在緊急闌尾切除術可以常規使用。闌尾炎是最常見的腹部急症且需要進行緊急手術,這樣會增加術後的併發症,其中最常見的就是傷口感染。標準預防方式是給予抗生素治療。為了減少醫療費用、藥物毒性及產生細菌抗藥性,建立最短且有效的預防性治療是值得期待的。這次研究回顧了解不管在闌尾切除之術前、術中或術後使用預防性抗生素,對於預防術後併發症是有效的。

Plain language summary

Antibiotic prophylaxis could be considered for routine in emergency appendectomies.

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention. This is associated with increased risk of postoperative complications, wound infection being the most commonly reported. Standard prophylaxis is an anti-bacterial treatment. In order to reduce cost, toxicity and the risk of developing bacterial resistance, it is desirable to establish the shortest and most effective prophylaxis for postoperative complications.
This review reports that antibiotic prophylaxis is effective in the prevention of postoperative complications in people who had the appendix removed. Regardless whether the antibiotic was given before, during or after the surgery.

Background

Appendicitis is the most common cause of acute abdominal pain requiring surgical intervention, and affects all age groups. On suspicion of acute appendicitis the standard procedure is surgery.
The number of patients undergoing appendectomy (removal of the appendix) in the population is significantly higher than the number of diagnosed acute appendicitis. Fenyö (Fenyö1995) reported that 15-30% of all appendectomies are unnecessary due to a non-inflamed appendix, and Luckmann (Luckmann 1989) suggests even higher numbers. The actual incidence of acute appendicitis varies, the overall lifetime risk for acute appendicitis is 6-20% (Blewett 1995; Addiss 1990). Addiss reported 8.6% for males and 6.7% for females, compared to an overall life time risk for appendectomy of 12% (males) and 23.1% (females) in US.
Removal of the appendix is most frequently reported in adolescents (10-20 years of age). The incidence in children under the age of 5, and in adults over 70 years of age, is small (Graffeo 1996; Addiss 1990; Luckmann 1989).

The cause of acute appendicitis is unclear. The mechanism of pathogenesis could involve obstruction of the appendiceal lumen, preventing the escape of intraluminal secretion (Arnbjörnsson 1983). This could result in increased intraluminal pressure, leading to transmural tissue necrosis . However, the mechanisms of pathogenesis continue to be debated.
The predominant microbial flora associated with acute appendicitis are E.Coli, Kleibciella, Proteus and Bacteroides (Altemeier 1938; Leigh 1974; Bennion 1990; Blewett 1995). These microbes may cause postoperative infection depending on the degree of inflammation of appendix, surgical technique and duration of operation. Postoperative complications parallel that found from perforated viscus of any cause. The most common being intra abdominal abscess and wound infection was reported in as high as 40% of all appendectomy cases (Almqvist 1995). Despite improved asepsis and surgical techniques, postoperative infections still accounts for morbidity and increased length of stay in hospital as major consequences.
Several studies have implicated that postoperative infections are reduced by the administration of antimicrobial regimes. The general assumption is that it is better to treat patients with complicated appendicitis with antibiotics than with placebo, in contrast to patients with simple appendicitis. Yet other studies have questioned the use of antibiotics at all in appendectomised patients. In order to reduce cost, toxicity and the risk of developing bacterial resistance, it is desirable to establish the shortest and most effective prophylaxis for postoperative complications.

Bearing the above points in mind, and given that the use of antibiotics in clinical practice is frequently questioned, in this systematic review we examined the effect of antimicrobial treatment versus placebo treatment in appendectomised patients. To reflect the clinical decision-making process we wanted to explore whether patients operated on suspicion of appendicitis could prevent postoperative infection if they received antimicrobial therapy prior to surgery or during surgery. This implicates that appendectomy is carried out for reasons other than acute appendicitis (negative appendectomy), and is included in this study as well, due to exposure of the colonic microbial flora.

A description of the alternatives to antimicrobial prophylaxis, such as delayed closure and surgical lavage, will not be covered in this review.

The clinical diagnosis of appendicitis is generally divided in two subgroups:

Simple appendicitis include terms like 'non-inflamed' (normal appendix), 'acutely inflamed', 'phlegmonous', 'acute', 'suppurative', 'mildly inflamed with or without peritonitis'. This condition also covers minimal appendicitis, early appendicitis, and uncomplicated appendicitis.
Complicated appendicitis includes 'gangrenous appendicitis', 'perforated appendicitis', 'local pus collection at operation', 'general peritonitis', and 'intra abdominal abscess'.

The analyses are stratified to include subgroups of patients with simple appendicitis and complicated appendicitis.

Objectives

A systematic search for relevant literature from controlled clinical trials was performed to find evidence relating to the use of antibiotics in patients undergoing appendectomy on the suspicion of appendicitis.
Relevant data were extracted from these reports of clinical trials and analysis performed which reflects the clinical decision-making process. Given the fact, that patients are operated upon suspicion of appendicitis, we wished to explore whether postoperative infection and prolonged stay in hospital could be prevented if the patients were given antimicrobial therapy prior to, under, or after the surgery.

Methods

Criteria for considering studies for this review

Types of studies

This review evaluated randomised controlled trials (RCTs) and controlled clinical trials (CCTs) in which treatment with any antimicrobial regime was compared to placebo in patients with suspected appendicitis undergoing appendectomy. The authors did not discriminate between trials that describe appendices in various stages, that is if they are non inflamed or perforated.
Studies in which the antimicrobial regime was compared to a control group receiving no treatment were excluded from this review, unless perioperative treatment was stated and subject blinding was found adequate.

Types of participants

Children and adults with suspected appendicitis based on either clinical conditions or intra operatively diagnosed by the surgeon. No restrictions to age or gender.

Appendectomised patients were ideally reported in two subgroups: Simple appendicitis and complicated appendicitis. If pathology was not stated in a trial, the data were admitted statistically into the subgroup 'appendicitis', which covers all aspects of pathology.

The definition of 'simple appendicitis' includes the appendix which is normal at operation (non-inflamed); acutely inflamed; phlegmonous; acute; suppurative; mildly inflamed with or without peritonitis. This condition also covers minimal appendicitis; early appendicitis; and uncomplicated appendicitis.
The definition of 'complicated appendicitis' includes gangrenous appendicitis; perforated appendicitis; local pus collection at operation; general peritonitis; and intra abdominal abscess.
Trials reporting patients with periappendicular abscess not operated upon are excluded from this review.

Types of interventions

Trials comparing any antimicrobial regime versus placebo administered before, during, or after appendicectomy, and reporting postoperative infection, length of stay in hospital, and mortality, were considered for this review.

The primary topic was to examine whether antimicrobial therapy given to patients operated on suspicion of appendicitis could prevent postoperative infection.

The types of intervention are specified in the table of comparisons.

The term 'clinical diagnosis' refers to the condition pre- or perioperatively diagnosis, usually performed by the clinician. The use of paraclinical diagnosis (bloodtest, urintest e.g.) is included in this term.

The term 'pathoanatomical diagnosis' refers to the more accurate postoperative diagnosis in which the nature of the removed appendix have been established either macroscopically or microscopically.

Trials reporting patients treated topically with antimicrobial agents disolved in aqueous solution were considered for inclusion if the comparison group was treated with the aqueous solution. Otherwise we excluded the study.

Types of outcome measures

Trials were considered if one or more of the following clinical outcomes were reported:

1) Wound infection (discharge of pus from the wounds).

2) Postoperative intra abdominal abscess (persistent pyrexia without any other focus, after operation, palpable mass in the abdomen or discharge of pus from the rectum).

3) Length of stay in hospital

4) Mortality

In this review we analysed patients with a normal appendix and patients with perforated appendix. This approach considered the pathoanatomical distinction of appendicitis, using the terms for subgroup analysis as described above.

Search methods for identification of studies

The following bibliographic databases were searched in order to identify relevant primary studies:

Cochrane Central Register of Controlled Trials (CENTRAL), Cochrane Library 2005 issue 1
PubMed, from 1966 to April 2005
EMBASE, from 1980 to April 2005
Cochrane Colorectal Cancer Group Specialised Register, April 2005

The following strategy was used to search the Pubmed database, combined with the Cochrane Collaboration highly sensitive search strategy for identifying randomised controlled trials and controlled clinical trials:

#1 appendic*
#2 appendec*
#3 appendek*
#4 #1 or #2 or #3
#5 apendic*
#6 apendec*
#7 apendek*
#8 #5 or #6 or #7
#9 appendix*
#10 apendix*
#11 #9 or #10
#12 #4 or #8 or #11

From the studies identified with the search term appendix* we have excluded Boon*, Spong*, Neuro* and Psyc*.

The Cochrane Central Register of Controlled Trials (CENTRAL) and CCCG specialised register were searched using the above search strategy, but without the Cochrane Collaboration highly sensitive search strategy for identifying randomised controlled trials and controlled clinical trials.

The search strategies were then combined with free text words (truncation as indicated):

#1 antibiot*
#2 antimic*
#3 metronida*
#4 #1 or #2 or #3

All identified trials from the search were evaluated for inclusion. Identified and included studies were further examined for additional studies from the respective reference list. .

The EMBASE database was searched using the following strategy. Search string from #22 to #33 describes the filter used for identification of randomised controlled trials and controlled clinical trials:

#35 #29 or #34
#34 #21 and #33
#33 random*
#32 #29 or #31
#31 #21 and #28
#30 case*
#29 #21 and #27
#28 random* or clin*
#27 #22 or #24 or #26
#26 #23 not #25
#25 'case-control-study' / all subheadings
#24 'randomization-' / all subheadings
#23 explode 'controlled-study' / all subheadings
#22 explode 'clinical-trial' / all subheadings
#21 #19 not #20
#20 boon* or spong*
#19 #17 not #18
#18 neuro* or psyc*
#17 #8 and #16
#16 #11 or #15
#15 #12 or #13 or #14
#14 metronida*
#13 antimic*
#12 antibiot*
#11 #9 or #10
#10 explode 'antibiotics-and-their-derivatives' / all subheadings
# 9 explode 'antibiotic-agent' / all subheadings
# 8 #1 or #7
# 7 #5 or #6
# 6 #2 or #3 or #4
# 5 'appendectomy-' / all subheadings
# 4 'appendix-perforation' / all subheadings
# 3 'acute-appendicitis' / all subheadings
# 2 'appendicitis-' / all subheadings
# 1 append* or apend*

The final number was manually searched for trials fulfilling the inclusion criteria.

This update revealed 11 new eligible studies, of which five were considered for inclusion (Harahsheh 2002; McGreal 2002; Taylor 2000; Taylor 2004; Simpson 2002). The remaining six trials described interventions outside the scope of this review. None of the five studies fulfilled the inclusion criteria for various reasons. One study was an abstract (Simpson 2002) and is awaiting assessment, and the four studies were excluded as described in the table of characteristics of excluded studies

Data collection and analysis

Appropriate criteria for assessing the quality of the included studies are methods (either qualitative or quantitative) that combine searches, outcomes, and meta-analysis.

Location and selecting studies:
All identified trials were reviewed independently by two authors (HKA and BRA) in order to evaluate, whether the trial should be included or should be excluded. A data extraction form was prepared prior to the search for literature. Disagreements were solved in an consensus meeting eventually with help from a third author.
Excluded studies were detailed in the table of excluded studies.

Critical appraisal of studies:
The methodological quality of each trial was assessed by the same two authors. Details of the randomisation method, blinding, and the number of patients lost during the study were recorded. When necessary information was missing from a published trial, the primary author were contacted for clarification.

Collecting data:
Data was independently extracted using a standard data extraction form. Recorded data was cross-checked. The data was entered into Metaview in RevMan 4.2.6 for analysis. The following parameters were extracted: wound infections; intra abdominal abscesses; number of days in hospital; and mortality.

Results

Description of studies

See: Characteristics of included studies; Characteristics of excluded studies.

Forty-five studies, including 9576 patients, were included in the meta-analyses of this review. Twelve studies had more than one arm; seven studies had two arms and five studies had three arms. Age-range of the included patients was three months to 94 years of age. Sixteen studies reported the male/female ratio. The morphologic descriptions of the pathoanatomical distinction of appendicitis were very weakly described. Twenty-one of the studies did not divide the appendix into pathological subgroups. Twenty-one of the studies reported a division into simple or complicated appendicitis. No attempt was made to elucidate age- or gender related correlations.
In summary, including the arms of all identified studies we examined 63 trials; 46 trials examined single drug therapy and 17 trials examined a combination of two or more drugs. The antibiotics used in the studies were divided into nine major antibiotic groups. The most common antibiotics used were Cephalosporin and imidazole derivatives.
All forty-five studies reported wound infection. Twelve studies reported intra abdominal abscess and ten studies reported length of stay in hospital. Only two studies reported mortality.

Thirty-two of the identified studies were excluded for various reasons, and one study is awaiting assesment (Simpson 2002). Allocation concealment being the major factor, followed by insufficient information on treatment strategies. Sixteen of those were potentially eligible for the meta-analysis, but any doubt on subject blinding led to their exclusion. In eleven of the studies the patients in the placebo group received no treatment. In nine studies, the antibiotics in the treatment group was administrated in a way, that made it possible for the patient as well as the clinician to know whether the patient was in the treatment group or in the control group. These studies were excluded because of inadequate blinding (Amgwerd 1981, Bates 1974, Bröte 1976, Evans 1973, Feltis 1967, Gómez-Alonso 1984, Kling 1985, McLean 1983, Okubadejo 1976). Two trials (Crosfill 1969, Gilmore 1975) were excluded because it was unclear which patients received systemic antibiotics. Yet another three studies described interventions that could make it difficult to establish the effect of antibiotics alone (Harahsheh 2002; Taylor 2000; Taylor 2004). One trial (Birkigt 1989) was excluded due to discord in the table of the results. Another trial (Herrera-Garcia 1985) did not distinguish between wound infection and intra abdominal abscess in the result section. Yet another study was excluded due to irrigation with physiological serum in the control group (Badia 1994).
Five studies did not fulfil the inclusion criteria for any meta-analyses. Two of the trials did not have results on appendicitis exclusively (Dixon 1984, Pollock 1972) and one (Rambo 1972) only reported one case of appendicitis. One trial was an abstract which did not obtain all the necessary details and it was impossible to get the full study. One trial were based on prior published trials (Leigh 1978). A detailed description is available in the reference list under "excluded studies".

Risk of bias in included studies

The methodological quality of each trial were assessed by the same two authors (HKA and BRA). Details of the randomisation method, blinding, and the number of patients lost during the study were recorded.
Missing information from reports of trials was sought by contacting the authors.
As a common denominator studies were excluded if the placebo group was not stated. However, if subject blinding was adequately described, studies reporting "control" or "no treatment" were considered for peri-operatively treatment only .

The randomisation method of included studies was adequately defined in 17 of the 45 studies, either by computerised random numbers or sealed envelopes. In twenty-three studies the randomisation method was not stated. The last five studies were indexed as quasi-randomised (CCT), by using birth date as concealment method. These studies were all categorised as having inadequate randomisation. Thirty of the studies were double or triple blinded. Ten of the studies had at least blinding of the patient, but unclear blinding of surgeon and outcome assessor. In five of the studies the blinding was found unclear.
Six studies displayed odd numbers in the comparison groups. They were individually evaluated for drop-outs or other reasons to clarify the imbalance and were finally included.
Wound infection was defined in 34 of the studies. The definition differed, but the major description was discharge of pus from the wounds. Three out of eleven studies defined intra abdominal abscess.
We did not observe any time related variations regarding the methodological quality of the studies. Older studies such as Stoller 1965 were found to be adequately randomised and fully comparable to newer studies.

Effects of interventions

Study validation in meta-analysis
In the current updated systematic review we have identified a total of 78 RCT's and CCT's for inclusion, of which 32 studies were excluded for various reasons. One trial is awaiting assessment.

In the first published version of this systematic review, we identified 70 RCT's and CCT's, of which 27 were excluded. In the first updated version (2003) we identified additional three studies, one was included and two were excluded. In this updated version we identified additional five studies, four excluded and one awaiting assessment.
Forty-five controlled trials (9576 patients), of which five trials were dealing with topical use of antibiotics, were included in the meta-analysis of this review. Outcome measures were sought divided in either simple or complicated appendicitis according to the definition in "types of participants". If no attempt was made to sub-divide the patients, results were presented as "appendicitis". Results are pooled data from all studies and focus on appendectomied patients without specification of the clinical severity of disease or pato-anatomic characterisation of the removed appendix. Analyses of pato-anatomic clinical relevant entities (normal removed appendix, simple appendicitis (phlegmonuos) or complicated appendicitis (gangrenous or perforated) confirmed the overall result: An effect of antibiotics when compared to placebo. A subgroup analysis of different treatment strategies (see table 1) confirmed this overall result.

The clinical heterogeneity
amongst the trials was reflected in parameters such as study population; diagnosis; strategy of treatment; type of antibiotics; the outcome analysis and length of follow up. The majority of included studies did not distinguish between adults and children. Six trials exclusively on children (a total of 776 patients, aged 3 months - 15 years of age) were reported. Included studies were different in strategy and use of antibiotics but all compared to placebo or control treatment (subject blinded).

The statistical heterogeneity depends on the clinical and methodological differences within the trials. We used a validated quality scale (Jadad 1996) in order to identify systematic differences among the included trials. This scale produces scores from 0-5 points. Trials with less than 3 point considered "poor quality studies". Each of the included trials was quality assessed independently by two of the three authors and the scores were compared.
Visual inspection of trials sorted by either size or quality score did not affect the outcome. Therefore, it was decided not to exclude low score studies.
To assess publication bias we used the regression test for asymmetry in the funnel plot a specified cut-off number of five trials in the meta-analysis was chosen. In total we performed visual inspection for asymmetry in a total of nine different outcomes, without detecting any discrepancies. This finding further supports the notion, that small trials show the same results as greater trials.
Sub-group analysis after randomisation may introduce bias due to significantly different population sizes. In addition, we observed that some of the included studies were unequally randomised as 3:2 or 2:1 and even 2:1:1 in multiple arm studies. Observed imbalance in the comparisons groups were evaluated to ensure an effect of the study design or any drop-outs on the overall results. Reasons for odd numbers in comparisons group were either multiple arm studies (Donovan 1979 A, Foster 1981 A, Viitanen 1984 A), unequally numbers of post-operative drop-outs or other reasons (Azabache 1987 A, Gledhill 1983, Keiser 1983, Stoller 1965).
In summary, we found that none of the included 45 studies revealed any significant discrepancy from the overall result. Conclusively, the statistical and clinical heterogeneity of the trials included in this review still make comparison of the individual trials possible with respect to the overall question - antibiotics versus placebo (no treatment).

Outcomes:
The major outcome "wound infection" was described in all included trials. However it must be emphasised, that the definition of wound infection is subject to a broad variety and in 9 of the 45 included trials no description was stated. In addition, clinical test for wound infection was also subject to broad variety in the studies describing this parameter.
The outcome "intra abdominal abscess" was described in 16 of the 45 included trials.
The outcome "length of hospital stay" was described in nine of the 45 included trials. Despite a marked heterogeneity among the trials, we decided to present the meta-analysis. The overall tendency in the included trials was no intention of describing the length of follow-up.
The outcome "mortality" was described in two trials with a total of three deaths. One patient died from lung emboli after three months, another from cardiac infarction and a third from peritonitis due to a perforated appendix. Therefore, no direct comparison was made possible, and no meta-analysis was made.

Study groups and results:
Thirty-four of the included trials include patients with all clinical aspects of appendicitis. The meta-analysis of this review are presented according to the clinical distinguishable diagnosis:
normal removed appendix, simple appendicitis (phlegmonuos) or complicated appendicitis (gangrenous or perforated).
The overall result is that the use of antibiotics is superior to placebo for the outcomes "wound infection" and "intra abdominal abscess".

None of the 45 trials described "exclusion of children", rather a variety in age for included patients. seven trials exclusively on children (776 patients, aged 3 months - 15 years) were reported, and the resulting meta-analysis showed non-significant effects.

Four trials examined topical application of antibiotics compared to placebo ( 679 patients). The meta-analysis did not show a significant effect.

Treatment strategies and subgroup results are presented in 'comparisons and data'. The drugs are administered either systemic or topical, without distinguishing between antibiotic regimens. Time of administration was divided in either pre- or peri-operatively, as the term post-operatively from a clinical point of view is irrelevant and not reported in the studies. However, the later may be relevant with one of the two former.

Number of drugs used is characterised as either 'single agent' or 'multiple agents'. Frequency of administration is divided in either 'single dose' or 'repetitive dose'.

The results are presented summarically as Peto/odds ratio (95% CI), fixed-effect model (log scale ranging from 0.01 to 10.00 shown in the meta-analysis graphs). Values less than 1.0 favour treatment with antibiotics. In addition the numerical values are notified as incidences/included patients for each Group (antibiotics versus placebo). The overall result shows a significant advantage for the use of antibiotics compared to administration of placebo.

Discussion

Recent studies have produced significant evidence to support the use of antibiotic therapy in patients undergoing appendectomy. We therefore tested the hypothesis:

"Does antibiotic treatment reduce post-operative infection rates in appendectomised patients"?

Antibiotic prophylaxis is one of many measures that should be taken into account in order to reduce postoperative morbidity (primarily wound infection). Many have reviewed the value of antimicrobial prophylaxis in clean-contaminated, contaminated and in clean operations, but even though benefits are well established, no general recommendations on antibiotic prophylaxis have been settled. This systematic review focus on appendectomised patients, randomly assigned either antibiotic therapy or placebo (control) treatment. Recommended duration of antibiotic administration is not possible from the presented meta-analysis, as we did not compare single dose versus multiple dose. In addition, the efficacy of the therapeutic use of different antibiotic regimens efficacy was not the scope of this review.
From a clinical point of view, the main concern on administration of antibiotics is how to reduce post surgical complications and the intention to shorten the length of the hospital stay. We did not address the use of antibiotics in the treatment of appendicitis without surgery.

The results confirm an overall effect of antibiotics, regardless administered as either prophylactics (single dose administration) in case of "normal removed appendix" or "simple appendicitis"(phlegmonous), or as repetitive treatment in case of "complicated appendicitis" (gangrenous or perforated).

Wound infection (superficial) or intra abdominal abscess (deep infection) are the most common post surgical complications and reflect the severity of disease and/or quality of surgical procedure. Long-term complications such as intestinal obstruction and infertility are not addressed in the included controlled studies with short follow up period, but need analysis from large epidemiological trials.
The outcome "length of hospital stay" is closely associated with the nature of post surgical infections and indirectly to the efficacy of antibiotics. A limited number of placebo controlled studies reviewed the length of hospital stay (Bates 1980, Bauer 1989, Busuttil 1981 A, Gurry 1976, Keiser 1983, Paakkonen 1982, Raahave 1970, Winslow 1983). From a historical point of view, we have to emphasise radical changes in "hospital stay policy", presently favouring early hospital discharge.
In summary, the presented meta-analysis on this parameter is based on studies from the past three decades and therefore difficult to interpret.

Mortality is a rare complication to appendectomy and only reported in two trials. Since the main outcome is short term investigation on the effect of antibiotic versus placebo on wound infection and intra abdominal abscess, this could explain the low number of reported deaths due to exclusion from study. Only one trial reported short term mortality as a reason for exclusion of patients from the study. An overview on actual mortality rate should be sought in epidemiological studies rather than randomised studies.

Seven trials exclusively on children (age: 3 months -15 year) were identified. Both nature of disease and treatment were comparable to the ones for adults. Interestingly, subgroup analysis of this population showed a non-significant reduction in infection rate, which can be explained by a limited number of patients without heterogeneity between single study results. Another factor is the reported pathogenesis of appendicitis in children, which shows higher incidence of complicated appendicitis. However, although not divided in specific sub-populations, the majority of studies include children in their analysis. It is only reasonable to assume that the overall antibiotic efficacy also is representative for children. Several non-randomised studies have revealed differences in the pathology of the diagnosed appendicitis which could explain the non-significant reduction in the infection rate.

The meta-analysis on topical use of antibiotics shows clinical heterogeneity, primarily explained in a reported diversity of experimental set-up. Eklund 1987 exclude all patients with perforated appendicitis and Gurry 1976 only include those patients. Eklund 1987 exclude patients treated with additional antibiotics before randomisation and Stoller 1965 exclude those patients after randomisation. Gurry 1976 and Foster 1981 A do not describe their procedure. In addition, the trials use four types of antibiotics and different ways of administration. Eklund 1987 and Gurry 1976 use a solution, Foster 1981 A uses powder and Stoller 1965 uses an aerosol. Regarding statistical heterogeneity, the trials express some methodological differences as well. Three of the trials are randomised-controlled trials and one of the trials is a controlled clinical trial. Foster 1981 A uses single blinding (patients), Eklund 1987 double blinding, and Gurry 1976 and Stoller 1965 triple-blinding.
Therefore, non-significant results could be explained by clinical and methodological differences. Historically, topical use of antibiotics is now generally replaced with a higher hygienic standard.

Wound infection is significantly reduced in pooled data as well as subgroup analysis, without any indication of statistical heterogeneity, confirmed by quality assessment of single studies, where high quality studies were compared to low quality studies without discrepancies in the effect parameter. Only deviance from this pattern is the non-significant result from topical use of antibiotics.

The meta-analysis of intra abdominal abscess show identical patterns, but only the analyse of the pooled data is statistical significant. Interestingly, the subgroup analysis show non-significant effect of antibiotics, which can be explained by the limited number of patients / events rather than heterogeneity or study quality.

We analysed the efficacy of antibiotics, administered either prophylactic or post-surgically, notified as "short term versus long term treatment". Both strategies reduces wound infection significantly and intra abdominal abscess non-significantly (again due to a low number of events). Although significant results we are not in a position of comparing these strategies, which needs to be adressed in a review comparing the different regimens.

Authors' conclusions

Implications for practice

It seems reasonable to conclude that antibiotic prophylaxis is effective in the prevention of post-operative complications in appendectomied patients, whether the administration is given pre-, per- or post-operatively, and should be considered for routine use in emergency appendicectomy. The overall strategy (type of antibiotics and/or preferred time of administration) needs to be evaluated in another systematic review.

Our results indicate that single doses have the same impact as multiple doses. In order to reduce cost, toxicity and the risk of developing bacterial resistance, it is desirable to establish the shortest, effective prophylaxis for post-operative complications, and from the meta-analysis it seem that single doses have the same impact as multiple doses.

The general assumption is that it is better to treat patients with complicated appendicitis with antibiotics than with placebo, in contrast to patients with simple appendicitis. Yet other studies have questioned the use of antibiotics at all in appendectomised patients.

Implications for research

Despite the presented meta-analysis indicate similar results on single dose efficacy and multiple dose efficacy, we did not compare these outcome parameters. In addition, the time for administration did not seem to have any significant impact at all, but weren't compared either. Conclusively these parameters should therefore be reviewed. Other strategies such as irrigation and delayed closure could alternatively have positive effects on reduction of postoperative complications, but need further examination in another systematic review.
This review confirms the effect of antibiotics in reducing wound infection and abscess formation in all pato-anatomic subgroup and after removal of a normal appendix. Recommendations to the use of antibiotics in all cases of appendectomies patients is still controversy regarding the general accepted recommendations prescribing only use of antibiotics in case of complicated appendicitis. On the other hand the literature stated superior effects following preoperatively administration incompatible to per operatively verifying (by visualisation) of the disease severity as condition for initialisation of antibiotic treatment.

Acknowledgements

We are specially grateful for a careful reading, valuable comments and suggestions from the peer reviewers, Dr. Roland Andersson, Department of surgery, Rykov Hospital, Jönköping Sweden, and Professor Mario Lise, University Hospital, Padova, Italy, and the key editor of the manuscript, Professor Ole Kronborg, Odense University Hospital, Denmark.
And for the incoming suggestions for improvenment from various colleagues.

Data and analyses

Download statistical data

Comparison 1. Systemic Antibiotics vs Placebo (Clinical)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection478812Peto Odds Ratio (Peto, Fixed, 95% CI)0.33 [0.29, 0.38]
1.1 Appendicitis212343Peto Odds Ratio (Peto, Fixed, 95% CI)0.31 [0.24, 0.42]
1.2 Simple appendicitis265317Peto Odds Ratio (Peto, Fixed, 95% CI)0.37 [0.30, 0.46]
1.3 Complicated appendicitis241152Peto Odds Ratio (Peto, Fixed, 95% CI)0.28 [0.21, 0.38]
2 Postoperative intra abdominal abscess164468Peto Odds Ratio (Peto, Fixed, 95% CI)0.43 [0.25, 0.73]
2.1 Appendicitis81033Peto Odds Ratio (Peto, Fixed, 95% CI)0.35 [0.13, 0.91]
2.2 Simple appendicitis82968Peto Odds Ratio (Peto, Fixed, 95% CI)0.46 [0.23, 0.94]
2.3 Complicated appendicitis4467Peto Odds Ratio (Peto, Fixed, 95% CI)0.54 [0.12, 2.43]
3 Length of stay in hospital81200Mean Difference (IV, Fixed, 95% CI)-1.69 [-1.78, -1.61]
Analysis 1.1.

Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 1 Wound infection.

Analysis 1.2.

Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 2 Postoperative intra abdominal abscess.

Analysis 1.3.

Comparison 1 Systemic Antibiotics vs Placebo (Clinical), Outcome 3 Length of stay in hospital.

Comparison 2. Systemic antibiotics vs placebo (Pathoanatomic)
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection211704Peto Odds Ratio (Peto, Fixed, 95% CI)0.32 [0.22, 0.47]
1.1 Normal appendix211555Peto Odds Ratio (Peto, Fixed, 95% CI)0.28 [0.18, 0.44]
1.2 Perforated appendicitis6149Peto Odds Ratio (Peto, Fixed, 95% CI)0.47 [0.22, 1.00]
2 Postoperative intra abdominal abscess3741Peto Odds Ratio (Peto, Fixed, 95% CI)0.28 [0.08, 0.91]
2.1 Normal appendix3673Peto Odds Ratio (Peto, Fixed, 95% CI)0.45 [0.10, 1.98]
2.2 Perforated appendicitis168Peto Odds Ratio (Peto, Fixed, 95% CI)0.12 [0.02, 0.86]
Analysis 2.1.

Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 1 Wound infection.

Analysis 2.2.

Comparison 2 Systemic antibiotics vs placebo (Pathoanatomic), Outcome 2 Postoperative intra abdominal abscess.

Comparison 3. Topical Antibiotics vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection4679Peto Odds Ratio (Peto, Fixed, 95% CI)0.77 [0.49, 1.23]
1.1 Appendicitis2113Peto Odds Ratio (Peto, Fixed, 95% CI)0.65 [0.27, 1.54]
1.2 Simple appendicitis2399Peto Odds Ratio (Peto, Fixed, 95% CI)1.30 [0.64, 2.64]
1.3 Complicated appendicitis2167Peto Odds Ratio (Peto, Fixed, 95% CI)0.43 [0.18, 1.01]
2 Postoperative intra abdominal abscess00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Lenght of stay in hospital129Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 3.1.

Comparison 3 Topical Antibiotics vs Placebo, Outcome 1 Wound infection.

Analysis 3.3.

Comparison 3 Topical Antibiotics vs Placebo, Outcome 3 Lenght of stay in hospital.

Comparison 4. Pre-operatively administered single agent, single dose Antibiotics vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection112191Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.25, 0.45]
1.1 Appendicitis2234Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.14, 0.80]
1.2 Simple appendicitis91514Peto Odds Ratio (Peto, Fixed, 95% CI)0.37 [0.25, 0.54]
1.3 Complicated appendicitis8443Peto Odds Ratio (Peto, Fixed, 95% CI)0.29 [0.18, 0.47]
2 Postoperative intra abdominal abscess2446Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.05, 2.45]
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis2382Peto Odds Ratio (Peto, Fixed, 95% CI)0.34 [0.05, 2.45]
2.3 Complicated appendicitis164Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital1121Mean Difference (IV, Fixed, 95% CI)0.40 [-0.01, 0.81]
Analysis 4.1.

Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 1 Wound infection.

Analysis 4.2.

Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 2 Postoperative intra abdominal abscess.

Analysis 4.3.

Comparison 4 Pre-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 3 Length of stay in hospital.

Comparison 5. Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection2215Peto Odds Ratio (Peto, Fixed, 95% CI)0.14 [0.05, 0.39]
1.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.12 [0.02, 0.61]
1.2 Simple appendicitis182Peto Odds Ratio (Peto, Fixed, 95% CI)0.16 [0.04, 0.59]
1.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2 Postoperative intra abdominal abscess00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 5.1.

Comparison 5 Pre-operatively administered multiple agent, single dose Antibiotics vs Placebo, Outcome 1 Wound infection.

Comparison 6. Per-operatively administered single agent, single dose Antibiotics vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection123358Peto Odds Ratio (Peto, Fixed, 95% CI)0.43 [0.34, 0.55]
1.1 Appendicitis6585Peto Odds Ratio (Peto, Fixed, 95% CI)0.37 [0.22, 0.60]
1.2 Simple appendicitis62347Peto Odds Ratio (Peto, Fixed, 95% CI)0.52 [0.37, 0.73]
1.3 Complicated appendicitis5426Peto Odds Ratio (Peto, Fixed, 95% CI)0.35 [0.21, 0.58]
2 Postoperative intra abdominal abscess32115Peto Odds Ratio (Peto, Fixed, 95% CI)0.67 [0.32, 1.42]
2.1 Appendicitis2380Peto Odds Ratio (Peto, Fixed, 95% CI)0.69 [0.12, 3.99]
2.2 Simple appendicitis11554Peto Odds Ratio (Peto, Fixed, 95% CI)0.74 [0.31, 1.79]
2.3 Complicated appendicitis1181Peto Odds Ratio (Peto, Fixed, 95% CI)0.32 [0.03, 3.29]
3 Length of stay in hospital2209Mean Difference (IV, Fixed, 95% CI)-0.80 [-1.34, -0.26]
Analysis 6.1.

Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 1 Wound infection.

Analysis 6.2.

Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 2 Postoperative intra abdominal abscess.

Analysis 6.3.

Comparison 6 Per-operatively administered single agent, single dose Antibiotics vs Placebo, Outcome 3 Length of stay in hospital.

Comparison 7. Per-operatively administered multiple agent, single dose Antibiotics vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection4216Peto Odds Ratio (Peto, Fixed, 95% CI)0.23 [0.12, 0.45]
1.1 Appendicitis3161Peto Odds Ratio (Peto, Fixed, 95% CI)0.24 [0.11, 0.52]
1.2 Simple appendicitis143Peto Odds Ratio (Peto, Fixed, 95% CI)0.19 [0.04, 0.89]
1.3 Complicated appendicitis112Peto Odds Ratio (Peto, Fixed, 95% CI)0.25 [0.03, 2.52]
2 Postoperative intra abdominal abscess00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 7.1.

Comparison 7 Per-operatively administered multiple agent, single dose Antibiotics vs Placebo, Outcome 1 Wound infection.

Comparison 8. Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection3256Peto Odds Ratio (Peto, Fixed, 95% CI)0.16 [0.07, 0.36]
1.1 Appendicitis3256Peto Odds Ratio (Peto, Fixed, 95% CI)0.16 [0.07, 0.36]
1.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2 Postoperative intra abdominal abscess2161Peto Odds Ratio (Peto, Fixed, 95% CI)0.12 [0.02, 0.89]
2.1 Appendicitis2161Peto Odds Ratio (Peto, Fixed, 95% CI)0.12 [0.02, 0.89]
2.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 8.1.

Comparison 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo, Outcome 1 Wound infection.

Analysis 8.2.

Comparison 8 Operatively single agent and post-operatively single agent, single dose Antibiotics vs placebo, Outcome 2 Postoperative intra abdominal abscess.

Comparison 9. Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection142097Peto Odds Ratio (Peto, Fixed, 95% CI)0.46 [0.35, 0.60]
1.1 Appendicitis81039Peto Odds Ratio (Peto, Fixed, 95% CI)0.45 [0.30, 0.68]
1.2 Simple appendicitis6875Peto Odds Ratio (Peto, Fixed, 95% CI)0.46 [0.30, 0.70]
1.3 Complicated appendicitis6183Peto Odds Ratio (Peto, Fixed, 95% CI)0.47 [0.24, 0.90]
2 Postoperative intra abdominal abscess3448Peto Odds Ratio (Peto, Fixed, 95% CI)0.14 [0.01, 1.30]
2.1 Appendicitis2269Peto Odds Ratio (Peto, Fixed, 95% CI)0.13 [0.01, 2.08]
2.2 Simple appendicitis1179Peto Odds Ratio (Peto, Fixed, 95% CI)0.15 [0.00, 7.38]
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital4434Mean Difference (IV, Fixed, 95% CI)-1.0 [-1.81, -0.19]
Analysis 9.1.

Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo, Outcome 1 Wound infection.

Analysis 9.2.

Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo, Outcome 2 Postoperative intra abdominal abscess.

Analysis 9.3.

Comparison 9 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo, Outcome 3 Length of stay in hospital.

Comparison 10. Operatively multiple agent and post operatively multiple agent, single dose Antibiotic vs Placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2 Postoperative intra abdominal absces00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Comparison 11. Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection6851Peto Odds Ratio (Peto, Fixed, 95% CI)0.18 [0.11, 0.27]
1.1 Appendicitis1200Peto Odds Ratio (Peto, Fixed, 95% CI)0.25 [0.10, 0.62]
1.2 Simple appendicitis4562Peto Odds Ratio (Peto, Fixed, 95% CI)0.20 [0.11, 0.35]
1.3 Complicated appendicitis589Peto Odds Ratio (Peto, Fixed, 95% CI)0.08 [0.03, 0.22]
2 Postoperative intra abdominal abscess3488Peto Odds Ratio (Peto, Fixed, 95% CI)0.38 [0.05, 2.72]
2.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.98 [0.06, 15.92]
2.2 Simple appendicitis2355Peto Odds Ratio (Peto, Fixed, 95% CI)0.15 [0.01, 2.38]
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital190Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 11.1.

Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, Outcome 1 Wound infection.

Analysis 11.2.

Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, Outcome 2 Postoperative intra abdominal abscess.

Analysis 11.3.

Comparison 11 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, Outcome 3 Length of stay in hospital.

Comparison 12. Systemic antibiotics vs Placebo in children
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection71090Peto Odds Ratio (Peto, Fixed, 95% CI)0.64 [0.37, 1.10]
1.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.98 [0.39, 2.44]
1.2 Simple appendicitis6704Peto Odds Ratio (Peto, Fixed, 95% CI)0.92 [0.33, 2.57]
1.3 Complicated appendicitis3253Peto Odds Ratio (Peto, Fixed, 95% CI)0.31 [0.12, 0.77]
2 Postoperative intra abdominal abscess61003Peto Odds Ratio (Peto, Fixed, 95% CI)0.29 [0.10, 0.83]
2.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.25 [0.05, 1.26]
2.2 Simple appendicitis5648Peto Odds Ratio (Peto, Fixed, 95% CI)0.14 [0.02, 0.98]
2.3 Complicated appendicitis2222Peto Odds Ratio (Peto, Fixed, 95% CI)0.78 [0.11, 5.70]
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 12.1.

Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 1 Wound infection.

Analysis 12.2.

Comparison 12 Systemic antibiotics vs Placebo in children, Outcome 2 Postoperative intra abdominal abscess.

Comparison 13. Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo in children
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection5953Peto Odds Ratio (Peto, Fixed, 95% CI)0.52 [0.29, 0.93]
1.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.98 [0.39, 2.44]
1.2 Simple appendicitis4598Peto Odds Ratio (Peto, Fixed, 95% CI)0.85 [0.26, 2.80]
1.3 Complicated appendicitis2222Peto Odds Ratio (Peto, Fixed, 95% CI)0.16 [0.06, 0.44]
2 Postoperative intra abdominal abscess6955Peto Odds Ratio (Peto, Fixed, 95% CI)0.29 [0.10, 0.83]
2.1 Appendicitis1133Peto Odds Ratio (Peto, Fixed, 95% CI)0.25 [0.05, 1.26]
2.2 Simple appendicitis5600Peto Odds Ratio (Peto, Fixed, 95% CI)0.14 [0.02, 0.98]
2.3 Complicated appendicitis2222Peto Odds Ratio (Peto, Fixed, 95% CI)0.78 [0.11, 5.70]
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 13.1.

Comparison 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo in children, Outcome 1 Wound infection.

Analysis 13.2.

Comparison 13 Operatively single agent and post-operatively single agent, multiple dose Antibiotic vs Placebo in children, Outcome 2 Postoperative intra abdominal abscess.

Comparison 14. Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, children
Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size
1 Wound infection150Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.2 Simple appendicitis150Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
1.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2 Postoperative intra abdominal abscess150Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.1 Appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.2 Simple appendicitis150Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
2.3 Complicated appendicitis00Peto Odds Ratio (Peto, Fixed, 95% CI)Not estimable
3 Length of stay in hospital00Mean Difference (IV, Fixed, 95% CI)Not estimable
Analysis 14.1.

Comparison 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, children, Outcome 1 Wound infection.

Analysis 14.2.

Comparison 14 Operatively multiple agent and post-operatively multiple agent, multiple dose Antibiotics vs placebo, children, Outcome 2 Postoperative intra abdominal abscess.

What's new

DateEventDescription
5 September 2008AmendedConverted to new review format.

History

Protocol first published: Issue 1, 1999
Review first published: Issue 2, 2001

DateEventDescription
20 April 2005New citation required and conclusions have changedSubstantive amendment

Contributions of authors

All three members were involved in the study design.
Two reviewers (BRA and HKA) were responsible for data extraction.
BRA and HKA performed all searches, determined inclusion, analysed the data.
All three reviewers wrote the report and performed the interpretation of the results and comments on early and final drafts of the report.
HKA performed the searches for the update of the review, April 2005.

Declarations of interest

None known

Sources of support

Internal sources

  • Copenhagen Hospital Corporation H:S, Denmark.

External sources

  • Danish Pharmacy Foundation of 1991, Denmark.

  • Danish Institute for Health Technology Assessment, Denmark.

Notes

In figure 12.2, a study (Soderquist A+B 1995) has been included for the outcome post-operative abdominal abcess. This study is not a new one, but was previously only presented in the figure 13.2.

Characteristics of studies

Characteristics of included studies [ordered by study ID]

Ahmed 1987

MethodsRandomised controlled trial. Randomisation method not stated.
Double-blinded. Unclear blinding of outcome assessor.
Participants190 patients enrolled in the study.
Age-range: Treatment group: 10-45, Placebo group: 10-40
Mean: Treatment group: 19,2 +/- 6,7 (s.d.), Placebo group: 21,3 +/- 8,7 (s.d.)
Patients with normal, gangrenous or perforated appendix and antibiotics prior to surgery were excluded before randomisation.
InterventionsTreatment group: Metronidazole 500 mg=100 ml i.v inter-operatively.
Placebo group: Saline 100 ml i.v peroperatively
OutcomesWound infection (Purulent discharge from the incision).
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Azabache 1987 A

MethodsRandomised controlled trial. Randomisation method stated as simple. Patient and surgeon blinded. Unclear blinding of outcome assesor.
Participants258 eligible patients. 92 excluded before randomisation. 166, 88 males and 78 females enrolled in the study.
Age-range: 6-71
Mean: 23
12 patients excluded after randomisation.
The study has 2 subgroups (see Azabache 1987 B).
In Azabache 1987 A 110 patients enrolled in study.
InterventionsTreatment group: Gentamycin 4 mg/kg and Clindamycin 15 mg/kg one hour inter-operatively hereafter Gentamycin eighthourly and Clindamycin sixhourly for 24 hours if appendix was suppurativ and 72 hours if appendix was gangrenous/perforated.
Placebo group: Not stated. Regime as above.
OutcomesWound infection (Pus in the cellular space under or above the rectusmuscle 3 weeks postoperatively)
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Azabache 1987 B

MethodsRandomised controlled trial. Randomisation method stated
Participants258 eligible patients. 92 excluded before randomisation. 166, 88 males and 78 females enrolled in the study.
Age-range: 6-71
Mean: 23
12 patients excluded after randomisation.
The study has 2 subgroups (see Azabache 1987 A).
In Azabache 1987 B 110 patients enrolled in study.
InterventionsTreatment group:
Penicilin G 400.000 UI/kg and Chloramphnicol 50 mg/kg one hour intra operatively. Hereafter penicillin G each four hour and chloramphenicol each six hour for 24 hours, if appendix was suppurative and 22 hours if appendix was gangrenous/perforated.
Placebo: Not stated. Regimen as above.
OutcomesWound infection (Pus in the cellular space under or above the rectusmuscle 3 weeks postoperatively)
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Bates 1980

MethodsControlled clinical trial. Random allocation by the admittiong house surgeon. No blinding of the patient. Adequate blinding of surgeon and unclear blinding of outcome assesor.
Participants200 eligible patients. 30 excluded after randomisation. 170, 90 males and 80 females enrolled in study.
Age-range: 0-90
InterventionsTreatment group: 1 g metronidazole supp 1 hour preoperatively and 1 g supp or orally 8 hourly postoperatively for 7 days. children below 12 received half dose.
Placebo group: No treatment
OutcomesWoundinfection (A frank discharge of pus)
Lenght of stay in hospital
NotesNo drain treatment
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Bauer 1989

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and out-come assessor.
Participants2387 eligible patients. 652 excluded after randomisation. 1735 enrolled in study.
Age-range: 3 months - 90 years. Mean 23
Patients with allergy to Cefoxitin or Cefalosoprins, moribund, in coma, impaired renal function, shock, antibiotics within 3 days, lactating and pregnant women, younger than 3 months of age were excluded before randomisation.
InterventionsTreatment group: Cefoxitin 2 g (children <12: 40 mg/kg) i.v inter-operatively.
Placebo group: No treatment.
OutcomesWound infection (Discharge of pus from the wounds occurring spontaneously or after incision).
Postoperative intraabdominal absces (Persistent pyrexia without any other focus, after operation, palpable mass in the abdomen or discharge of pus per rectum).
Length of stay in hospital
No postoperative deaths. One died from aorta aneurism, 1 from livercancer and 2 from thrombosis a. mesenterica.
NotesNo drain treatment.
Antibiotics administered 3-5 min before surgery.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Bergmark 1985

MethodsRandomised controlled trial. Randomisation method not stated.
Double-blinded. Unclear blinding of out-come assessor.
Participants183 eligible patients. 50 patients excluded after randomisation. 133 patients, 59 males and 74 females enrolled in the study.
Age-range: Treatment group: 16-72, Placebo group: 17-69
Mean: Treatment group 39, Placebo group 36
InterventionsTreatment group: Trimethoprim 240 mg and Sulfametizole 1200 mg and Metronidazole 1,5 g (15 ml) i.v preoperatively.
Placebo group: Saline 0,9% 15 ml i.v preoperatively.
OutcomesWound infection (Pus precent in the wounds or if microbiological culture was positive from a wound opening spontaneously or opened by a surgeon when an infefection was inspected).
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Browder 1989 A

MethodsRCT, Computer-generated double-blind trial
Participants175 eligible
122 enrolled
InterventionsCeftizoxime, Cefamandole versus placebo given IV pre-op and 6-12 hours after surgery
Three arm study
OutcomesWound infection (not defined)
NotesOnly Pt's with non-perforative appendicitis were enrolled
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Browder 1989 B

MethodsAs above
ParticipantsAs above
InterventionsAs above
OutcomesAs above
NotesAs above
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearD - Not used

Busuttil 1981 A

MethodsRandomised controlled trial. Randomisation from a masterlist outside the experimential protocol section.
Triple-blinded.
Participants189 eligible patients. 52 patients excluded after randomisation. 136 patients enrolled in study.
Age-range: 4-75, mean 23.
The study has 3 subgroups (see Busuttil 1981 B).
In Busuttil 1981 A 90 patients enrolled in the study.
Patients with perforated appendix, allergy to cephalosporins or penicillins, antibiotic therapy within 72 hours before surgery, pregnacy, inability to 30- days follow-up, serious underlying illnes expected to require antibiotic therapy, were excluded before randomisation.
InterventionsTreatment group: Cefamandole 2 g (children 100-150 mg/kg/day) and Carbenicillin 3 g (children 400-500 mg/kg/day) i.v preoperatively, 4 hours postoperatively and every 6 hour thereafter for 24 hours.
Placebo treatment: Equivalent volumes of dilution i.v preoperatively, 4 hours postoperatively and every 6 hour thereafter for 24 hours.
OutcomesWound infection (Collection of pus drained spontaneously or by incision).
Length of stay in hospital
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Busuttil 1981 B

MethodsRandomised controlled trial. Randomisation from a masterlist outsite the experimental protocol section.
Triple-blinded.
Participants189 eligible patients. 52 patients excluded after randomisation. 136 patients enrolled in the study.
Age-range: 4-75, mean 23
The study has 3 subgroups (see Busuttil 1981 A).
In Busuttil 1981 B 91 patients enrolled in the study.
Patients with perforated appendix, allergy to cephalosporins or penicillins, antibiotic therapy within 72 hours before surgery, pregnacy, inability to 30- days follow-up, serious underlying illnes expected to require antibiotic therapy, were excluded before randomisation.
InterventionsTreatment group: Cefamandole 2 g i.v preoperatively, 4 hours postoperatively and every 6 hours thereafter for 24 hours. Children 100-150 mg/kg/day.
Placebo treatment: Equivalent volume of dilution i.v preoperatively, 4 hours postoperatively and every 6 hours thereafter for 24 hours.
OutcomesWound infection (Collection of pus drained spontaneously or by incision).
Length of stay in hospital
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Chiam 1983 A

MethodsRandomised controlled trial. Randomisation by random numbers. Double-blinded. Unclear blinding of outcome assessor.
Participants400 eligible patients. 117 excluded after randomisation. 283 enrolled in the study.
All patients above 12 years of age.
Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated appendix were excluded before randomisation.
The study has 4 subgroups (see Chiam 1983 B & C).
In Chiam 1983 A 147 patients enrolled in study.
InterventionsTreatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days and Cotrimoxazole 2 ml i.m preoperatively and twice daily for 3 days.
Placebo group: Not specified, but administred as supp and i.m as regime above.
OutcomesWound infection (Pus in the main wound).
NotesPatients with the operative diagnosis of perforated appendix were included in the study.
No comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Chiam 1983 B

MethodsRandomised controlled trial. Randomisation by random numbers. Double-blinded. Unclear blinding of outcome assessor.
Participants400 eligible patients. 117 excluded after randomisation. 283 enrolled in study.
All patients above 12 years of age.
Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated appendix, were excluded before randomisation.
The study has 4 subgroups (see Chiam 1983 A & C).
In Chiam 1983 B 150 patients enrolled in the study.
InterventionsTreatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days.
Placebo group: Not specified, regime above.
OutcomesWound infection (Pus in the main wound).
NotesPatients with the operative diagnosis of perforated appendix were included in the study.
No comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Chiam 1983 C

MethodsRandomised controlled trial. Randomisation by random numbers. Double-blinded. Unclear blinding of outcome assessor.
Participants400 eligible patients. 117 excluded after randomisation. 283 enrolled in the study.
All patients above 12 years of age.
Patients already receiving antibiotics or steroids, diabetic and preoperative diagnosis of perforated appendix, were excluded before randomisation.
The study has 4 subgroups (see Chiam 1983 A & B).
In Chiam 1983 C 134 patients enrolled in the study.
InterventionsTreatment group: Cotrimoxazole 2 ml i.m preoperatively and twice daily for 3 days
Placebo group: Not specified, regime as above.
OutcomesWound infection (Pus in the main wound).
NotesPatients with the operative diagnosis of perforated appendix were included in study.
No comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Corbett 1979

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants105 patients enrolled in the study.
Age-range 5-70.
InterventionsTreatment group: Metronidazole 1 g supp preoperatively and eight-hourly for 3 days. (children <14: ½ dosis)
Placebo group: supp regime as above.
OutcomesWound infection (Definite cellulitis and pyrexia, copious seropurulent discharge)
NotesSome patients received drain.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Creve 1980 A

MethodsRandomised cotrolled trial. Randomisation by sealed envelopes. Blinding of patients and surgeon. Unclear blinding of outcome assesor.
Participants13 patients enrolled in the study.
Age-range: 18-76
InterventionsTreatment group: Gentamycin 80 mg i.v. inter-operatively.
Placebo group: No treatment
OutcomesWound infection (presense of pus which either spontaneously discharged or required evacuation)
NotesNo comments on drain treatment.
The results are a part of a study including other kind of gastrointestinal sugery.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Creve 1980 B

MethodsRandomised cotrolled trial. Randomisation by sealed envelopes. Blinding of patients and surgeon. Unclear blinding of outcome assesor.
Participants4 patients enrolled in the study.
Age-range: 18-76
InterventionsTreatment group: Gentamycin 80 mg and Clindamycin 600 mg i.v inter-operatively.
Placebo group: No treatment
OutcomesWound infection (presense of pus which either spontaneously discharged or required evacuation)
NotesNo comments on drain treatment.
The results are a part of a study including other kind of gastrointestinal sugery.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Donovan 1979 A

MethodsRandomised controlled trial. Randomisation based on a table of random numbers.
Patient blinded. Unclear blinding of surgeon and outcome-assesor.
Participants250 eligible patients.12 patients were excluded after randomisation. 238 patients were enrolled in the study. All patients above 12 years of age.
The study has 3 subgroups (see Donovan B).
In Donovan 1979 A 153 patients enrolled in the study.
Patients who received antibiotics within the previous 7 days before operation or had allergy to penicillin, were excluded before randomisation.
InterventionsTreatment group: Clindamycin 600 mg i.m preoperatively to the anaesthetized patient.
Placebo treatment: Saline 3 ml i.m preoperatively to the anaesthetized patient.
OutcomesWound infection (Discharge of pus from the wound either spontaneously or after incision).
One patient died 3 months postoperative from pulmonary embolism.
NotesDraining of the wound depending on surgeon. 14 patients in the treatment group were drained, 8 contracted wound infection. 12 patients in the placebo group were drained, 6 contracted wound infection.
Some patients received additional antibiotics starting more than 48 hours postoperatively.
Some patients received additional antibiotics starting within 48 hours postoperatively. They were excluded unless they developed a wound infection.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Donovan 1979 B

MethodsRandomised controlled trial. Randomisation based on a table of random numbers.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants250 eligible patients.12 patients were excluded after randomisation. 238 patients were enrolled in the study. All patients above 12 years of age.
The study has 3 subgroups (see Donovan A).
In Donovan 1979 B 157 patients enrolled in the study.
Patients who received antibiotics within the previous 7 days before operation or had allergy to penicillin, were excluded before randomisation.
InterventionsTreatment group: Cefazoline 1 g i.m preoperatively to the anaesthetized patient.
Placebo treatment: Saline 3 ml i.m preoperatively to the anaesthetized patient.
OutcomesWound infection (Discharge of pus from the wound either spontaneously or after incision).
One patient died 3 months postoperative from pulmonary embolism.
NotesDraining of the wound depending on surgeon. 15 patients in the treatment group were drained, 13 contracted wound infection. 12 patients in the placebo group were drained, 6 contracted wound infection.
Some patients received additional antibiotics starting more than 48 hours postoperatively.
Some patients received additional antibiotics starting within 48 hours postoperatively. They were excluded unless they developed a wound infection.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Eklund 1987

MethodsRandomised controlled trial. Randomisation by a list of random numbers.
Double-blinded. Unclear blinding of outcome assessor.
Participants510 eligible patients, 214 males and 296 females enrolled in the study.
All patients more than 12 years of age.
Patients with perforated appendix, treated with antibiotics for other disease and patients undergoing additional procedure were excluded before randomisation.
InterventionsTreatment group: Tinidazole 2 mg/ ml 200 ml topical peroperatively.
Placebo group: Saline 200 ml topical peroperatively.
OutcomesWoundinfection (Wound discharge visible pus either spontaneously or after debridement).
NotesNo comments on drain treatment.
180 patients had normal appendix.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

El-Sefi 1986 A

MethodsRandomised controlled trial. Randomisation based on a table of random numbers.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in the study.
Patients with perforated appendix were excluded after randomisation.
The study has 4 subgroups (see El-Sefi 1986 B & C).
In El-Sefi 1986 A 200 patients enrolled in the study.
InterventionsTreatment group: Metronidazole 500 mg IV preoperatively and eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 250 orally) and Cefazolin 500 mg i.v preoperatively and eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 250 orally).
Placebo group: Not specified, same regime as above
OutcomesWound infection (Presence of pus or a purulent exudate of the wound).
NotesNo comments on drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

El-Sefi 1986 B

MethodsRandomised controlled trial. Randomisation based on a table of random numbers.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in study.
Patients with perforated appendix were excluded after randomisation.
The study has 4 subgroups (see El-Sefi 1986 A & C).
In El-Sefi 1986 B 200 patients enrolled in the study.
InterventionsTreatment group: Metronidazole 500 mg i.v preoperatively and eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 250 orally) and Tobramycin 80 mg i.v preoperatively and eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 80 mg i.m).
Placebo group: Not specified same regime as above.
OutcomesWound infection (Presence of pus or a purulent exudate of the wound).
NotesNo comments on drain treatment
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

El-Sefi 1986 C

MethodsRandomised controlled trial. Randomisation based on a table of random numbers.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants480 eligible patients. 80 patients excluded after randomisation. 400 enrolled in the study.
Patients with perforated appendix were excluded after randomisation.
The study has 4 subgroups (see El-Sefi 1986 A & B).
In El-Sefi 1986 C 200 patients enrolled in the study.
InterventionsTreatment group: Metronidazole 500 mg i.v preoperatively and eight-hourly for the next 3 days. (When the patient tolerated oral medication converted to 250 orally)
Placebo group: Not specified same regime as above.
OutcomesWound infection (Presence of pus or a purulent exudate of the wound).
NotesNo comments on drain treatment
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Foster 1978

MethodsRandomised controlled trial. Randomisation based on a computer list kept by the hospital pharmacist. Triple-blinded
Participants165 eligible patients. 26 excluded after randomisation. 139, 74 males and 65 females enrolled in the study. Patients with perforated appendix and different infections such as pelvic inflammatory disease, were excluded after randomisation.
Patients with allergy to penicillin og cephalosporins, antibiotic administration 48 hours before surgery, expectation of need for antibiotic treatment in the immediate postoperative periode and impaired renal or hepatic function were excluded before randomisation.
InterventionsTreatment group: Cephaloridine 50 mg/kg i.m. The first dose given with preanaesthetic medication and postoperatively x4 daily for 2 days.
Placebo group: Not stated: Regime like the treatment group.
OutcomesWound infection (Not defined).
NotesNo comments on drain treatment
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Foster 1981 A

MethodsRandomised controlled trial. Randomisation methode not stated.
Doubleblinding. Unclear blinding of outcome assesor.
Participants496 patients enrolled in the study.
The study has 3 subgroups (see Foster 1981 B).
In Foster 1981 A 377 patients enrolled in the study.
InterventionsTreatment group: Metronidasole 1 g supp 40 min preoperatively.
Placebo group: Identical supp 40 min preoperatively.
OutcomesWound infection (not defined)
NotesSome patients got drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Foster 1981 B

MethodsRandomised controlled trial. Randomisation methode not stated.
Blinding of patient. No blinding of surgeon and unclear blinding of outcome assesor.
Participants496 patients enrolled in the study.
The study has 3 subgroups (see Foster 1981 A).
In Foster 1981 B 236 patients enrolled in the study.
InterventionsTreatment group: Povidone iodine dry powder per-operatively.
Placebo group: Nothing
OutcomesWound infection (not defined)
NotesSome patients got drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Giacomantonio 1982

MethodsRandomised controlled trial. Randomisation by random numbers in the pharmacy.
Triple-blinded.
Participants42 enrolled in the study.
Age-range: Pediatric.
Only patients with acute appendicitis without perforation.
Patients allergic to penicillin og cephalosporin were excluded before randomisation.
InterventionsTreatment group: Cefamandole 25 mg/kg i.v / i.m preoperatively and immediately postoperatively and 6 hours later.
Placebo group: Not specified, same regime as above.
OutcomesWound infection (Presence of pus in the wound or wound pain, tendernes or erythema or sufficient magnitude to interfere with the patient´s well-being or to prolong hospital stay).
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Gledhill 1983

MethodsClinical controlled trial. Allocation according to the month of their day of birth.
Blinding unclear.
Participants102 enrolled in the study.
mean: Treatment group: 24,9, placebo group: 26,2
Patients with weight less than 25 kg, pregnant women or steroid treatment were excluded before randomsation.
InterventionsTreatment group: Cefamandole 2 g i.v inter-operatively.
Placebo group: Nothing.
OutcomesWound infection (Not defined).
NotesAlle patients received drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Go 1986

MethodsRandomised controlled trial. Randomisation method not stated.
Doubleblinded. unclear blinding of outcome assesor.
Participants159 patients enrolled in the study.
Age-range: 12-79, Mean: 29,6
InterventionsTreatment group: Metronidazole 1 g in 100 ml saline IV inter-operatively.
Placebo group: Saline 100 ml inter-operatively.
OutcomesWound infection (not defined)
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Gottrup 1979

MethodsRandomised controlled trial. Randomisation by random numbers.
Double-blinded
Participants426 eligible patients. 20 patients were excluded after randomisation. 406 patients enrolled in the study. Age-range 5->50.
Patients with allergy to metronidazol, pregnant women, patients with blood dyscrasia, active disease of the central nervous system or alcoholism were excluded before randomisation.
InterventionsTreatment group: Metronidazole 500 mg = 100 ml i.v preoperatively.
Placebo group: 100 ml saline i.v preoperatively.
OutcomesWound infection (Superficial accumulation of pus requiring surgical drainage).
Postoperative intraabdominal abscess (Pyrexia, postoperatively for more than 72 hours, and for wich all other causes could be excluded; Abdominal tenderness or distension; Discharge of pus per rectum).
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Greenall 1979

MethodsRandomised controlled trial. Randomisation method not stated.
Double-blinded. Unclear blinding of outcome-assessor.
Participants116 eligible patients. 16 excluded before the code was broken. 111 patients, 51 males and 49 females enrolled in the study.
Age-range 5-73.
Mean 22 +/- 15 (s.d.) in treatment group, +/- 14 (s.d.) in placebo group.
InterventionsTreatment group: Metronidazole 500 mg in 100 ml saline i.v preoperatively.
Placebo group: Saline 100 ml i.v preoperatively.
OutcomesWound infection (Discharge of pus form the wound).
NotesDraining of the wound depending on surgeon. 5 patients in the treatment group were drained, none contracted wound infection. 9 patients in the placebo group were drained, 3 contracted wound infection.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Griffiths 1976

MethodsRandomised controlled trial. Randomisation method not stated.
Triple-blinded.
Participants28 enrolled in the study.
Patients with antibiotic treatment prior to surgery, pregnant women, or impaired renal function were excluded before randomisation.
Patients with perforated appendix were excluded after randomisation.
InterventionsTreatment group: Tobramycin 1,5 mg and Lincomycin 600 mg in 500 ml saline i.v peroperatively.
Placebo group: No treatment
OutcomesWound infection (Severe: Purulent discharge, cultures positive for potential pathogens; Mild: Erythema, scanty pus, cultures positive; Colonised: Not clinical infected, cultures positive).
NotesTreatment beginning at the time of skin incision .
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Gurry 1976

MethodsClinical controlled trial. Randomisation method not stated. Tripleblinded
Participants29 patients enrolled in study. All patients had perforated appendix
InterventionsActive group: Noxytioline 2,5 g in 100 ml saline instilled in the peritoneal cavity and the wound immediately before closure.
Placebo group: 100 ml saline instilled into the peritoneal cavity and the wound immediately before closure.
OutcomesWoundinfection (Not defined).
Length of stay in hospital
NotesNo drainage in either group.
Postoperative antibiotics were used in two control patients and in one patient in the treatment group. (Persisting peritonitis, chest infection, septicaemia)
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Harnoss 1986

MethodsRCT double blind
Participants175 eligible Pts
145 enrolled
No children under the age of 14 years of age
InterventionsOne shot 500 mg Metronidazole peri-operative, IV
versus placebo (not stated)
OutcomesWound infection in simple appendicitis
NotesNo perforated appendicitis are included.
An overview of other studies are described in table 4
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearD - Not used

Hutchinson 1983

MethodsRandomised controlled trial. Randomisation by numbered envelopes.
Double-blinding. Unclear blinding af outcome assessor.
Participants145 eligible patients. 12 excluded after randomisation. 133 patients, 91 males and 42 females enrolled in the study.
Age-range: 16 months - 15 years of age. Mean 6,7
InterventionsTreatment group: Metronidazole (0-3 years 125 mg, 3-6 years 250 mg, 7-15 years 500 mg) supp. preoperatively and eight-hourly for the next 72 hours.
Placebo group: Supp. preoperatively and eight-hourly for the next 72 hours.
OutcomesWound infection (Discharge of pus from the wounds).
Postoperative intraabdominal abscess (Not defined).
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Keiser 1983

MethodsRandomised controlled trail. Randomisation by random numbers.
Double-blinded. Unclear blinding of outecome assessor.
Participants98 eligibel patients, 26 excluded after randomisation. 98 enrolled in the study.
Age-range: 15-60. Mean: 27,5
Patients with active neurologic diseasis, blodd dyscrasia, hypothyroidism, hypoadrenalism, were pregnant, and patients who refused to enter the stydy were excluded.
InterventionsTreatment group: Metronidazole 1 g IV preoperatively and 500 mg eight-hourly 5 times.
Placebo treatment: Not specified. Regime as above.
OutcomesWound infection (Wound erythema, definitely infected or purulent discharge).
Length of stay in hospital
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Kekomäki 1983

MethodsRandomised clinical controlled trial on children
Participants115 eligible
91 enrolled
24 excluded due to various reasons
Interventionsmetronidazole versus placebo rectal suppositorium prior to surgery and 4 days follow up
OutcomesWound infection (not defined)
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kizilcan 1992 A

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants100, 66 males and 34 females enrolled in the study.
Age-range: 0-15.
Patients presenting parameters suggesting complicated appendicitis were not included.
The study has 4 subgroups (see Kizilcan 1992 B & C).
In Kizilcan 1992 A 50 patients enrolled in study study. 5 patients excluded after randomisation.
InterventionsTreatment group: Ornidazole 20 mg/kg/day divided in 2 doses initiated preoperatively.
Placebo group: Not specified in same regime as above
OutcomesWound infection (Not defined).
Postoperative intraabdominal abscess (Not defined).
NotesNo drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kizilcan 1992 B

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants100, 66 males and 34 females enrolled in the study.
Age-range: 0-15.
Patients presenting parameters suggesting complicated appendicitis were not included.
The study has 4 subgroups (see Kizilcan 1992 A & C).
In Kizilcan 1992 B 50 patients enrolled in the study. 5 patients excluded after randomisation.
InterventionsTreatment group: Penicillin 200.000 U/kg/day divided in 8 doses and Tobramycine 4 mg/kg/day divided i 3 doses initiated preoperatively.
Placebo group: Not specified in same regime as above
OutcomesWound infection (Not defined).
Postoperative intraabdominal abscess (Not defined).
NotesNo drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kizilcan 1992 C

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants100, 66 males and 34 females enrolled in the study.
Age-range: 0-15.
Patients presenting parameters suggesting complicated appendicitis were not included.
The study has 4 subgroups (see Kizilcan 1992 A & B).
In Kizilcan 1992 A 50 patients enrolled in the study. 6 patients excluded after randomisation.
InterventionsTreatment group: Piperacillin Na 200 mg/kg/day divided in 3 doses initiated preoperatively.
Placebo group: Not specified in same regime as above
OutcomesWound infection (Not defined).
Postoperative intraabdominal abscess (Not defined).
NotesNo drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Kortelainen 1982

MethodsClinical controlled trial. Allocation based on the last digit of the patients birth year.
Participants315 eligible patients, 278 enrolled. Age range 15-83 years, 159 males and 119 females
InterventionsTreatment group: Metronidazole suppository (1 g) 30-60 min preoperatively.
Control group: No antimicrobial therapy
OutcomesWound infection, defined as the presence of pus or a purulent exudate at the wound
NotesAppendicitis defined as either normal, inflamed or gangrenous
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Leigh 1976

MethodsClinical controlled trial. Randomisation method not stated. Double-blinded.
Participants200 patients, 103 males and 97 females enrolled in study. Age-range 0->40. Patients with macroscopic perforation of the appendix, pre-existing peritonitis or abscess formation were excluded.
InterventionsTreatment group: Lincomycin 600 mg = 2 ml i.m following closure of the wound.
Control group: Saline 2 ml i.m following closure of the wound.
OutcomesWound infection (Discharge of purulent fluid from the operation wound with associated inflammation of the skin edges).
Postoperative intraabdominal abscess (Not defined).
Notes6 patients in the treatment group and 2 patients in the placebo group had microscopic perforation of the appendix.
Draining of the wound depending on the surgeon. 8 patients in the treatment group were drained, none contracted wound infection. 6 patients in the placebo group were drained, 5 contracted wound infection.
11 patients in each group recieved additional antibiotics (Wound infection, urinary tract infection, postoperative chest infection).
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Morris 1980 A

MethodsRandomised controlled trial. Randomisation by a list of random numbers.
Double-blinded. Unclear blinding of outcome-assessor.
Participants340 eligble patients. 69 excluded after randomisation. 271 patients enrolled in the study.
The study has 4 subgroups (see Morris 1980 B & C).
In Morris 1980 A 133 patients enrolled in study.
All patients above 14 years.
Patients with diabetes or who received antibacterial or steroid treatment or had severe peritonitis requiring antibacterial therapy or had allergy to cephalosporin, were excluded before randomisation.
InterventionsTreatment group: Metronidazole 1 g suppositorium preoperatively and eight-hourly to a total of four doses.
Placebo group: Supp. preoperatively and eight-hourly to a total of four doses.
OutcomesWound infection (Presence of pus in the wounds).
NotesNo comments on drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Morris 1980 B

MethodsRandomised controlled trial. Randomisation by a list of random numbers.
Double-blinded. Unclear blinding of outcome-assessor.
Participants340 eligible patients. 69 excluded after randomisation. 271 patients enrolled in the study.
The study has 4 subgroups (see Morris 1980 A & C).
In Morris 1980 B 137 patients enrolled in the study.
All patients above 14 years.
Patients with diabetes or who received antibacterial or steroid treatment or had severe peritonitis requiring antibacterial therapy or had allergy to cephalosporin, were excluded before randomisation.
InterventionsTreatment group: Cefazolin 500 mg IV / IM preoperatively and eight-hourly to a total of four doses.
Placebo group: An injection i.v /i.m preoperatively and eight-hourly to a total of four doses.
OutcomesWound infection (Presence of pus in the wounds).
NotesNo comments on drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Morris 1980 C

MethodsRandomised controlled trial. Randomisation by a list of random numbers.
Double-blinded. Unclear blinding of outcome-assessor.
Participants340 eligble patients. 69 excluded after randomisation. 271 patients enrolled in the study.
The study has 4 subgroups (see Morris 1980 A & B).
In Morris 1980 C 133 patients enrolled in the study.
All patients above 14 years.
Patients with diabetes or who recieved antibacterial or steroid treatment or had severe peritonitis requiring antibacterial therapy or had allergy to cephalosporin, were excluded before randomisation.
InterventionsTreatment group: Metronidazole 1 g suppositorium and Cefazolin 500 mg i.v / i.m preoperatively and eight-hourly to a total of four doses.
Placebo group: Supp. and injection i.v / i.m preoperatively and eight-hourly to a total of four doses.
OutcomesWound infection (Presence of pus in the wounds).
NotesNo comments on drain treatment.
Wrote to author to specify subgrouping on drop-outs.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Paakkonen 1982

MethodsRandomised controlled trial. Randomisation by the anaesthetist.
Double-blinded. Unclear blinding of outcome-assessor.
Participants158 eligible patients. 27 patients excluded after randomisation. 131, 68 males and 63 females enrolled in the study.
Age-range: Treatment group 15-85, placebo group 15-80.
Mean: Treatment group 39,7, placebo group 35,5
InterventionsTreatment group: Metronidazole 500 mg IV preoperatively.
Placebo group: Saline 100 ml i.v preoperatively.
OutcomesWound infection (Accumulation of pus with spontanously or surgical drainage).
Postoperative intraabdominal abscess (Not defined).
Length of stay in hospital
NotesNo drain treatment.
Patients with perforated appendix all received antibiotics. That subgroup is excluded from this review.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Raahave 1970

MethodsRandomised controlled trial. Randomisation method not stated.
Double-blinded. Unclear blinding of outcome assessor.
Participants30 eligible patients. 2 patients excluded after randomisation. 28 enrolled in the study
Age-range: 3-70.
All patients had perforated appendix.
InterventionsTreatment group: Kanamycin 250-1000 mg depending on S-crea. first dosis topical, hereafter im.
Placebo group: Saline, regime as above.
OutcomesWound infection (Not defined).
Postoperative intra abdominal absces (Not defined).
Length of stay in hospital
No mortalities.
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Richards 1981

MethodsRandomised controlled trial. Both surgeon and outcome assessor are blinded
Participants143 eligible
129 enrolled
of which 55 had appendectomy
InterventionsGentamycin and glindamycin versu placebo
Outcomespost-operative infection
Notes 
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Rodgers 1979

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants102 eligible patients. 12 patients were excluded after randomisation. 90 patients enrolled in the study.
InterventionsTreatment group: Metronidazole 1 g suppositorium preoperatively and herafter 8 hourly the next 2 days.
Placebo group: Witepsol supp preoperatively and hereafter 8 hourly the next 2 days.
OutcomesWound infection (Pus or purulent exudate at the wound).
Postoperative intra abdominal abscess (Not defined).
NotesDraining of the wound depending on purulent peritoneal exudate, gangrenous/perforated appendix. 8 patients in the treatment group were drained, none contracted wound infection. 4 patients in the placebo group were drained, 3 contracted wound infection.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Rowlands 1982

MethodsRandomised controlled trial. Randomisation method not stated.
Triple-blinded.
Participants71 patients enrolled in the study.
Patients who were pregnant, clinical jaundiced, had chronic liver or renal disease, astma, eczema, impaired eight nerve function, had already recieved antibiotics or hypersensitivity were excluded before randomisation.
InterventionsTreatment group: Clindamycin 600 mg IV and Gentamycin 120 mg peroperatively. (=150 ml)
Placebo group: Glucose 150 ml i.v peroperatively
OutcomesWound infection (Discharge of purulent material from the wound or stitch sites or a nonpurulent discharge from wich a positive bacteriological culture was obtained).
NotesDrain treatment depending on surgeon.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Saario 1981

MethodsClinical controlled trial. Allocation based on the last digit of the patients birth year.
Participants203 eligible patients. 23 patients excluded after randomisation. 180 patients, 111 males and 69 females enrolled in the study.
All patients above 6 years of age.
Mean: Treatment group: 28,7 +/- 16,3 (s.d), Placebo group: 28,3 +/- 14,7 (s.d).
Patients with perforated appendix, receiving antibiotics 7 days before surgery, pregnant women, or active neurologic disease, were excluded before allocation.
InterventionsTreatment group: Metronidazole 500 mg IV (children half dose) inter-operatively after the surgeon had seen the state of the appendix.
Placebo group: Nothing
OutcomesWound infection (Discharge of pus from the wound either spontaneously or after incision).
Postoperative intra abdominal abscess (Not defined).
Length of stay in hospital
NotesNo comments on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Salo 1981

MethodsRandomised controlled trial. Randomisation method not stated.
Double-blinded. Unclear blinding of outcome assessor.
Participants223 eligible patients. 2 patients excluded after randomisation. 221 enrolled in the study.
Mean: Treatment group: 32,6, Placebo group: 32,7
InterventionsTreatment group: Tinidazole 500 mg in 100 ml saline i.v preoperatively.
Placebo group: Saline 100 ml properatively.
OutcomesWound infection (Presence of pus in the operation wound requiring surgical incision)
NotesNo comment on drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Sole 1982

MethodsRandomised controlled trial by use of sealed envelope.
Participants231 eligible pts 113 enrolled
withdrawals not stated
Interventions500 mg Metronidazole one shot peri-operatively. IV versus control
OutcomesWound infection (Presence of pus in the operation wound requiring
NotesNo children under the age of 12 years
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Stoller 1965

MethodsRandomised controlled trial. Randomisation by random cards. Triple-blinded.
Participants84 enrolled in the study.
Patients who were given systemic antibiotic immediate postoperatively were excluded after randomisation.
InterventionsTreatment group: Polybactrim spray, topical after closure of peritoneum.
Placebo group: Not specified, regime as above.
OutcomesWoundinfection (An inflammatory erythema in clear excess of normal healing process or if serum or pus discharged from the wound).
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Söderquist 1995 A

MethodsRandomised controlled trial
Randomisation method not stated
Participants857 eligible patients. 313 patients excluded after randomisation.
544 patients enrolled in study. Alle children.
Patients with perforated appendicitis were excluded. Patients allergic to antibiotics or recieving antibiotic within 72 hours before surgery were excluded. 193 patients received treatment compared to 176 in the control group
InterventionsTreatment group: metronidazole 20 mg/ kg IV 1 hour preoperatively.
Placebo group: No treatment
OutcomesWound infection (subcutaneus abscess with suppuration confirmed by spontaneus wound rupture debriemnt or incision)
Intrabadominal absces (absces within the intraabdominal cagvity diagnosed at operation or by rectal examination, x-ray or ultrasound)
NotesNo comment on drain treatment
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Söderquist 1995 B

MethodsRandomised controlled trial
Randomisation method not
Participants857 eligible patients. 313 patients excluded after randomisation.
544 patients enrolled in study. Alle children.
Patients with perforated appendicitis were excluded. Patients allergic to antibiotics or recieving antibiotic within 72 hours before surgery were excluded. 175 patients received treatment compared to 176 in the control group.
InterventionsTreatment group: Metronidazole 20 mg/kg + cefuroxime 50 mg/kg iv 1 hour preoperatively.
Placebogroup: no treatment
OutcomesWound infection (subcutaneus abscess with suppuration confirmed by spontaneus wound rupture debriemnt or incision)
Intrabadominal absces (absces within the intraabdominal cagvity diagnosed at operation or by rectal examination, x-ray or ultrasound)
NotesNo comment on drain treatment
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Tanner 1980

MethodsRandomised controlled trial. Randomisation method not stated.
Patient blinded. Unclear blinding of surgeon and outcome-assessor.
Participants111 eligible patients. 7 patients excluded. 104, 51 males and 53 females enrolled in the study.
Age-range 8-71
Mean: Treatment group: 26 +/- 14 (s.d.), placebo group: 25 +/- 15 (s.d)
InterventionsTreatment group: Metronidazole 1 g suppositorium preoperatively.
Placebo group: Glycerine supp preoperatively.
OutcomesWound infection (Presence of pus or a purulent exudate at the wound).
NotesDrain treatment to all patients with perforated appendix.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Viitanen 1984 A

MethodsClinical controlled trial. Allocation by birthday.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants588 eligible patients. 123 excluded after randomisation. 465 enrolled in the study.
Age-range: 15-94 Mean: 33,4
315 enrolled in this part of the study.
The study has 3 subgroups (see Viitanen 1984 B).
In Viitanen 1984 A 315 patients enrolled in study.
InterventionsTreatment group: Tinidazole 500 mg in 100 saline i.v preoperatively.
Placebo group: No treatment.
OutcomesWound infection (Pus from the wounds).
Two patients died, 1 of peritonitis induced by perforation of the appendix, 1 died of cardiac infarction.
NotesTreatment initiated on anaesthetized patient.
No drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Viitanen 1984 B

MethodsClinical controlled trial. Allocation by birthday.
Patient blinded. Unclear blinding of surgeon and outcome assessor.
Participants588 eligible patients. 123 excluded after randomisation. 465 enrolled in the study.
Age-range: 15-94 Mean: 33,4
315 enrolled in this part of the study.
The study has 3 subgroups (see Viitanen 1984 A).
In Viitanen 1984 B 327 patients enrolled in study.
InterventionsTreatment group: Tinidazole 500 mg in 100 saline IV preoperativly and 500 mg three time daily for three days.
Placebo group: No treatment.
OutcomesWound infection (Pus from the wounds).
Two patients died, 1 of peritonitis induced by perforation of the appendix, 1 died of cardiac infarction.
NotesTreatment initiated on anaesthetized patient.
No drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearD - Not used

Wayand 1982

MethodsRandomised controlled trial. Randomisation by a list of random numbers.
Blinding unclear.
Participants220 eligible patients. 25 excluded after randomisation. 195, 85 males and 110 females enrolled in the study.
Mean-age: 23
Patients who received antibiotics within the previous 3 days before operation, had allergy to antibiotics, were pregnant, and breast-feeding women, patients with kreatinin >3 mg%, and patients who denied consent, were excluded before randomisation.
InterventionsTreatment group: Cefamandol 2 g IV preoperatively and eight-hourly altogether 5 doses.
Placebo group: Not specified 2 g iv preoperatively and eight-hourly altogether 5 doses.
OutcomesWound infection (Not defined).
NotesNo comments on drain treatment
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?YesA - Adequate

Willis 1976

MethodsRandomised controlled trial, method not stated
Participants105 eligible pt
95 enrolled
10 pts excluded due to prior antibiotic record or failure in randomisation procedure
InterventionsMetronidazole versus placebo as suppository for seven days
Outcomeswound infection
(discharge from the wound)
NotesAll suppositories contain Witepsol 35 and 75
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?UnclearB - Unclear

Winslow 1983

MethodsRandomised controlled trial. Randomisation by the last number in the patients birthday.
Triple-blinded.
Participants147 eligible patients. 44 excluded after randomisation. 103 enrolled in the study.
Age-range 4-67. Mean 22.
Patients receiving antibiotics 72 hours prior of surgery, had allergy to cephalosporins or penicillin, had impaired renal function and serious underlying disease, were excluded before randomisation
InterventionsTreatment group: Cefoxitin 1 g (children 20-40 mg/kg/dose) IV peroperatively and 6 and 12 hours postoperatively.
Placebo group: Saline regime as above.
OutcomesWound infection (Not defined).
Postoperative intra abdominal abscess (Not defined)
Length of stay in hospital
NotesNo drain treatment.
Risk of bias
ItemAuthors' judgementDescription
Allocation concealment?NoC - Inadequate

Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion
Amgwerd 1981Adequate randomisation, but control group received no treatment, and treatment group received pre-operative and post-operative IM treatment which means inadequate blinding and the results of infection may be biased.
Andersen 1972All patients received post-operative antibiotic.
Badia 1994The treatment group (antibiotics) is compared to a 'control group' receiving a solution with physiological serum.
Bates 1974Randomisation by sealed envelopes. Control group received no treatment, and treatment group received peri-operative topical treatment which means inadequate blinding and the results of infection may be biased.
Birkigt 1989Randomised clinical trial. There are discord in the table of results. The number of patients differ within the same groups.
Birkigt 1991Unknown allocation consealment and odd distribution numbers in the treatment group versus control group.
Bröte 1976Randomisation not stated. Control group received no treatment, and treatment group received postoperative IV treatment which means inadequate blinding and the results of infection may be biased.
Calman 1971Abstract. It has been impossible for the reviewers to get a full study.
Crosfill 1969Randomised controlled trial. Systemic antibiotics were given as supplement to topical treatment to the most seriously ill. The author does not describe which patients that get systemic antibiotics.
Dixon 1984The trial group is patients in elective and emergency operations. No reports on appendicitis exclusively.
Evans 1973Randomisation by toss of a coin. Control group received no treatment, and treatment group received postoperative IM treatment which means inadequate blinding and the results of infection may be biased.
Everson 1977Insufficient subject blinding. Patients receiving post-operative injection three times compared to control group (no treatment)
Feltis 1967Randomisation method not stated. Control group received no treatment, and treatment group received pre-operative, peri-operative and post-operative IV treatment, which means unclear blinding, and the results of infection may be biased.
Gilmore 1973Inadequate allocation consealment
Gilmore 1975Randomisation by af table of random numbers. Unclear which patients received systemic antibiotic treatment within the topical treatment and placebogroup.
Gómez-Alonso 1984Adequate randomisation, but control group received no treatment, and treatment group received pre-operatively and post-operative IM treatment which means inadequate blinding and the results of infection may be biased.
Harahsheh 2002Randomised single blin trial, in which all pts received daily antiseptic dressings with povidone-iodine (10% in alcohol).
Herrera-Garcia 1985Adequate randomisation, but no differentiation between wound infection and intra-abdominal abscess in the result section.
Kling 1985Adequate randomisation, but control group received no treatment, and treatment group received preoperative IV treatment 1-3 hours prior to operation, which means unclear blinding and the results of infection may be biased.
Leigh 1978A study based on prior publised trials, of which we have included one, excluded one (not randomised), and yet another not possible to identify.
Marti 1978Initially three arm study comparing two different antibiotics, which later becomes a two-arm study. No indication of wound infection - only abscesses are described.
McGreal 2002All pts received antibiotic prophylaxis. Clinical question focuses on two different ways of wound closure.
McLean 1983Adequate randomisation. Control group received no treatment, and treatment group received post-operative IV and orally administrated treatment, which means inadequate blinding and the results of infection may be biased.
Okubadejo 1976Randomisation by Fisher´s tabels. Control group received no treatment, and treatment group received post-operative treatment which means inadequate blinding and the results of infection may be biased.
Pietila 1982No statement of placebo/control and any indication of withdrawal of patients.
Pollock 1972The treatment group is composed of abdominal surgery, potentially contaminated operations. No reports on appendicitis exklusively.
Rambo 1972Randomisation adequate. The trial include miscellaneous emergency surgery, of which only one appendectomy was reported.
Tanphiphat 1978Unclear what treatment is given to who post-operatively. In addition, wound lavage is offered all enrolled pt, so it is difficult to establish a clear effect of antibiotic treatment.
Taylor 2000Both comparisons groups received antibiotic treatment
Taylor 2004Both comparisons groups received antibiotic treatment. The protocol seem identical to the Taylor 2000 reference
Walsh 1981Unclear what treatment is given to who post-operative. From table 1, there is a clear distinction between antibiotics and control group. From table 3 it is difficult to establish a clear effect of antibiotic treatment. Therefore we decided to exclude the study.
Willis 1979A summary of metronidazole in the prevention and treatment of anaerobic sepsis, in which appendicitis is a part. Seems identical to prior publication in 1976 (which is included)

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