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Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults

  1. Richard Pugh1,*,
  2. Chris Grant2,
  3. Richard PD Cooke3,
  4. Ged Dempsey2

Editorial Group: Cochrane Acute Respiratory Infections Group

Published Online: 5 OCT 2011

Assessed as up-to-date: 9 MAR 2011

DOI: 10.1002/14651858.CD007577.pub2


How to Cite

Pugh R, Grant C, Cooke RPD, Dempsey G. Short-course versus prolonged-course antibiotic therapy for hospital-acquired pneumonia in critically ill adults. Cochrane Database of Systematic Reviews 2011, Issue 10. Art. No.: CD007577. DOI: 10.1002/14651858.CD007577.pub2.

Author Information

  1. 1

    Glan Clwyd Hospital, Department of Anaesthetics, Rhyl, Denbighshire, UK

  2. 2

    University Hospital Aintree, Department of Critical Care, Liverpool, Merseyside, UK

  3. 3

    University Hospital Aintree, Department of Microbiology, Liverpool, Merseyside, UK

*Richard Pugh, Department of Anaesthetics, Glan Clwyd Hospital, Rhyl, Denbighshire, LL18 5UJ, UK. pughr@hotmail.com.

Publication History

  1. Publication Status: Edited (no change to conclusions)
  2. Published Online: 5 OCT 2011

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This is not the most recent version of the article. View current version (24 AUG 2015)

 
Characteristics of included studies [ordered by study ID]
Bouadma 2010

MethodsThe PRORATA study. A multi-centre study based in France. Unblinded, randomised controlled trial comparing strategy utilising serum procalcitonin measurement to guide initiation and cessation of antibiotics for ICU patients with suspected bacterial infection, with antibiotic administration according to an agreed guideline


Participants630 adult ICU patients (8 medical, surgical or medical-surgical ICUs; 6 hospitals). Mean age was 62; 66% male; SAPS II 47; SOFA score 7.8) with suspected bacterial infection (either at admission or during ICU stay). 89% patients were medical.16% enrolled patients were defined as being "Immunocompromised" (including patients with AIDS, solid organ transplant, haematological malignancy, prior chemotherapy or radiotherapy, and long-term corticosteroid or other immunosuppressant therapy); identifying and excluding data from these patients for the purpose of the systematic review was not possible. There appear not to have been significant differences in baseline characteristics between treatment groups. Of 621 patients entered into the analysis, 214 (34%) had VAP or "HAP": 141 (23%) patients were diagnosed with VAP, and 73 (12%) patients had HAP not requiring mechanical ventilation. For all patients with microbiologically-confirmed infection, initial antibiotic therapy was appropriate in 92% cases. Diagnostic criteria for VAP and HAP were not provided in the full-text article

Exclusions: pregnancy, expected ICU stay < 3 days, bone marrow transplant or chemotherapy-induced neutropenia, infections requiring long-term course antibiotic therapy (e.g. infective endocarditis), poor chance of survival (SAPS II > 65), DNR order


InterventionsPatients randomised to intervention group (311 randomised; 4 withdrew consent; 307 included in analysis; 75 patients with VAP; 29 with HAP not requiring mechanical ventilation) had serum procalcitonin level measured at inclusion, at each infectious episode until day 28, and for every morning that antibiotics were administered. The guidance for withholding or stopping antibiotic therapy was: i. antibiotics to be withheld when procalcitonin was < 0.5 µg/L on day of study entry; ii. antibiotics to be discontinued when procalcitonin level had fallen to < 0.5 µg/L or to less than 20% of the peak procalcitonin concentration

For patients randomised to control group (319 randomised; 4 withdrew; 1 randomised twice; 314 included in analysis; 66 patients with VAP; 44 patients with HAP not requiring mechanical ventilation), physicians were encouraged to administer antibiotics according to agreed recommendations (including duration of therapy)


OutcomesMost outcome data were presented for all patients, without specific reference to patients with VAP or HAP (non-ventilated)

For all patients, the following outcomes were presented:

  • Mortality (28-day and 60-day)
  • Number of days without antibiotics (28-day)
  • Relapse or superinfection (28-day)
  • Mechanical ventilation-free days (28-day)
  • SOFA scores (Days 1, 7, 14, 21 and 28)
  • Duration of stay in ICU
  • Duration of stay in hospital
  • Days of exposure to each antibiotic per 1000 patient days
  • Number of days of continuous antibiotic treatment (28-day)
  • Duration of antibiotic treatment according to infection site
  • Percentage of emerging multi-drug resistant bacteria isolated from routine microbiological assessment (28-day)


For patients specifically with VAP, the following outcomes were presented:

  • Duration of first episode of antibiotic treatment
  • Number of days without antibiotics (28-day)
  • Mortality (28-day)


NotesProcalcitonin measurements were used to guide whether to initiate antibiotic therapy as well as when to discontinue therapy. A very low proportion of recruited patients were surgical, which may limit generalisability of results. There was a high incidence of protocol non-adherence; the algorithm for antimicrobial therapy administration was not followed (overall) in 162 patients (53%) in the intervention group, nor for 141 patients in the control group (45%). For all patients, a non-significant increase in 60-day mortality was observed in the procalcitonin group (92/307 (30%) versus 82/ 314 (26.1%)] in the control group). Furthermore, the study may have been under-powered to determine non-inferiority of PCT-guided therapy in terms of death, since it was based upon a 35% absolute mortality in the control group and a 10% between-group mortality difference. For all patients, in the procalcitonin group there were non-significantly greater relapse rates (20/ 307 (6.5%) versus 16/ 314 (5.1%) in control group; P = 0.45) and superinfection rates (106/ 307 (34.5%) versus 97/ 314 (30.9%) in the control group; P = 0.29)


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Independent, centralised, computer-generated randomisation sequence... was used to randomly assign patients."

Allocation concealment (selection bias)Low risk"Investigators were masked to assignment before... randomisation."

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded study

Incomplete outcome data (attrition bias)
All outcomes
Low risk2 patients lost to follow-up, 1 from intervention and 1 from control group. This is unlikely to have a clinically relevant impact

Selective reporting (reporting bias)Unclear riskUnclear

Other biasHigh riskThe algorithm for antimicrobial therapy administration was not followed (overall) in 162 patients (53%) for the intervention group, nor for 141 patients in the control group (45%)

Chastre 2003a

MethodsThe PNEUMA study, a multi-centre study based in France. Unblinded, randomised controlled trial comparing fixed durations (8-day versus 15-day) of antibiotic therapy for VAP. Randomisation occurred 3 days after bronchoscopy confirming diagnosis of VAP


Participants401 adult patients. 51 French ICUs. 72% male; mean age 61; episodes due to NF-GNB 32.5%, MRSA 11.2%; mean SAPS II score 45; mean SOFA score 7.4 at admission. VAP was diagnosed according to the following criteria: new and persistent radiographic infiltrate, plus 1 of: purulent tracheal secretions, temperature of 38.4 °C or higher, or leukocyte count > 10,000/µL; and positive quantitative culture of 104 cfu/mL from BAL or 103 cfu/mL from PSB. Duration of mechanical ventilation prior to VAP: 13.6 days. No significant differences between groups at baseline, with the exception of significantly higher proportion of men (76.6%) in 8-day regimen versus men in 15-day regimen (67.6%; P = 0.046). All patients received appropriate initial antibiotics. Exclusions included early onset pneumonia (within 5 days of commencing mechanical ventilation) in patients who had received no antimicrobial therapy in the 15 days prior to diagnosis of pneumonia, and immunocompromised state, characterised by: neutropenia, AIDS, long-term corticosteroids or other immunosuppressant therapy


Interventions197 patients received fixed 8-day course of antibiotics (chosen by treating physician); 204 patients received a 15-day course


OutcomesThe following outcome measures were reported:

  • Death from any cause (28-day and 60-day)
  • Microbiologically-confirmed pulmonary infection recurrence (28-day)
  • Antibiotic-free days (28-day)
  • Mechanical ventilation-free days (28-day)
  • Number of organ failure-free days (28-day)
  • Evolution of parameters comprising the SOFA score and ODIN score (Day 1 to 28)
  • Clinical features relevant to pulmonary infection (fever, leukocyte count, PaO2/ FiO2 ratio, radiologic score; Day 1 to 28)
  • Duration of stay ITU
  • Rate of unfavourable outcome (death, recurrence, prescription of new antibiotic therapy)
  • In-hospital mortality
  • Percentage of emerging multiresistant bacteria during ITU in bronchoscopic samples collected to investigate possible recurrence


NotesRepeat bronchoscopy was performed on the basis of fever, purulent secretions, new or progressive pulmonary infiltrates, or deterioration in respiratory or haemodynamic parameters. It was not performed routinely, e.g. on completion of 8-day course of therapy, and consequently data regarding persistent colonisation with NF-GNB is not available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low risk"Randomisation was performed...and stratified... according to a computer-generated random-number table."

Allocation concealment (selection bias)Low risk"Randomisation performed centrally, using an interactive voice system... randomisation was not communicated to the investigators until day 8... On that day, investigators had to telephone the randomisation centre to receive the treatment assignment by fax."

Blinding (performance bias and detection bias)
All outcomes
High risk"...Patients, medical and nursing staffs, and pharmacists remained blinded until [day 8]." However, importantly, no attempt was made to blind from day 8, i.e. the point from which thereafter allocation might make a significant difference

Incomplete outcome data (attrition bias)
All outcomes
Low riskFollowing randomisation, 0 patients were lost to follow-up. 1 patient excluded from analysis following withdrawal of consent

Selective reporting (reporting bias)Unclear riskStudy protocol not available for examination. However, outcome measures are those expected and appropriately presented within the report

Other biasLow riskThere was a significantly higher proportion of men in the 8-day group (76.6%) compared with the 15-day group (67.6%; P = 0.046). However, there were not significant differences in illness severity scores, prior duration of mechanical ventilation, prior antibiotic administration, micro-organisms responsible for VAP, and antibiotic regimes to treat VAP

Data regarding proportions of patients who contrary to protocol did not receive a full 8-day or 15-day course of antibiotics are not provided. However, absolute antibiotic-treatment days and 28-day antibiotic-free day data indicates significantly less antibiotic exposure as a consequence of allocation to short or prolonged-course therapy

Fekih Hassen 2009

MethodsSingle-centre study based in Tunisia. RCT comparing fixed durations (7-day versus 10-day) of antibiotic therapy for VAP


ParticipantsMedical ICU. 30 adult patients (63% male; mean age 63 years; NF-GNB 72%; SAPS II 42.4). VAP (onset more than 48 hours after mechanical ventilation in ICU) diagnosed was suspected on the basis of: new and persistent radiographic infiltrate, purulent secretions, fever or deteriorating gas exchange or white cell count and confirmed on quantitative analysis of culture of endotracheal aspirate (> 104 cfu/ml) or protected distal respiratory specimens (>103 cfu/ml). Mean onset of VAP after institution of mechanical ventilation: 10 days. Initial antibiotics were appropriate in 94% of cases. No significant differences in baseline characteristics between the 2 groups

Exclusions include: second episode of pneumonia during single hospitalisation, terminal illness, failure to isolate bacterial growth

30 patients randomised from 39 patients with clinical features of VAP: 9 not enrolled because of terminal illness or failure to isolate bacteria


Interventions14 patients randomised to receive 7-day course of antibiotics; 16 patients to receive 16-day course. Choice of antibiotic: on microbiology advice, taking into account whether early (up to including 5 days after commencing mechanical ventilation) or late-onset VAP, and whether risk factors for multi-resistant bacteria present, and modified according to culture/sensitivity results

94% patients received appropriate initial antibiotic therapy


OutcomesThe following outcome measures were presented:

  • Mortality (14-day and 28-day)
  • Antibiotic-free days (28-day)
  • Microbiological resolution (timescale not specified)
  • CPIS resolution (days 1, 10, 14)
  • Mechanical ventilation-free days (28-day)
  • Recurrence: relapse or super-infection (timescale not specified)
  • Duration of ITU stay


NotesData regarding protocol violations and patients lost to follow-up not available. Unable to make contact trial with authors to request supplementary information


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskUse of random number table

Allocation concealment (selection bias)Unclear riskInadequately reported

Blinding (performance bias and detection bias)
All outcomes
Unclear riskInadequately reported

Incomplete outcome data (attrition bias)
All outcomes
Unclear riskInadequately reported

Selective reporting (reporting bias)Unclear riskInadequately reported

Other biasLow riskNo evidence of other source of bias

Medina 2007

Methods2 centre study, based in Uruguay, conducted May 2003 to December 2006 (during the period December 2005 to April 2006 recruitment was interrupted while eligible patients were enrolled in the Pontet 2007 study). Randomised controlled study comparing fixed short (8-day) and long (12-day) courses of antibiotic therapy for VAP.


Participants77 patients (medical, surgical and neurosurgical; mean age 59 years, 53% male, 63.6% NF-GNB, 9.1% MRSA; median APACHE II score 21, MODS score 5, SOFA score 6) with VAP. VAP was diagnosed on the basis of: new and persistent radiographic infiltrates, 2 of temperature ≥38.5 ºC or <36 ºC, leukocytes ≥12,000/ mm3 or ≤ 4 x103/ mm3, and BAL culture ≥ 104 cfu/ml, or positive ETA plus CPIS > 6, or micro-organism in ≥ 2 blood cultures with identical sensitivity to tracheal secretions and in absence of other possible infection, or positive culture of pleural fluid. Mean time after commencing mechanical ventilation before onset of VAP: 9.3 days. 68% patients had received a prior course of antibiotics. In 97% cases, initial antibiotic therapy for VAP was appropriate. There were no significant differences in baseline characteristics between treatment groups
Exclusion criteria: failure to meet clinical and microbiological criteria, decision not to institute antibiotic therapy, duration of therapy < 6 days, death before 6th day of treatment, onset of VAP within 48 hours of admission from other centre


Interventions77 patients randomised to 8-day treatment or 12-day course on Day 8 of antibiotic therapy. Antibiotic choice was that of the attending physician; in 75/77 (97%) cases, initial antibiotic therapy was appropriate. The most commonly used antibiotics were: cefoperazone-sulbactam, carbapenem and other third-generation cephalosporins. In 51% cases, antibiotic combinations were used


OutcomesThe following outcomes were studied:

  • ITU mortality
  • VAP-related mortality
  • Clinical resolution of VAP
  • Non-resolution of VAP ("Therapeutic failure")
  • Recurrence of VAP
  • Duration of mechanical ventilation


Notes0 patients were lost to follow-up. No patient received a shorter duration of antibiotic therapy than allocated; data incomplete for patients who had antibiotics continued beyond the allocated duration


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation using random number table

Allocation concealment (selection bias)Low riskSealed, numbered envelopes opened sequentially

Blinding (performance bias and detection bias)
All outcomes
High riskUnblinded study

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo patients lost to follow-up

Selective reporting (reporting bias)Unclear riskUnclear. Data incomplete for patients who had antibiotics continued beyond the allocated duration

Other biasLow riskStudy appears to be free of other sources of bias

Micek 2004

MethodsSingle-centre, medical ICU from USA. Randomised controlled study comparing strategy involving discontinuation policy to decrease antibiotic administration for VAP with standard-therapy


Participants302 patients receiving antibiotic treatment for VAP were randomised. VAP was diagnosed on the basis of: new persistent radiographic infiltrates together with one of: positive pleural culture (same organism as in sputum/tracheal aspirate), radiographic cavitation, histopathologic evidence of pneumonia, or 2 of: fever, leukocytosis and purulent tracheal aspirate or sputum. Mean age 60 years; 50% male; 29% COPD; APACHE II score 23; mean CPIS 7.1; Pseudomonas or Acinetobacter infection 11%; MRSA 20%. 25% patients had received prior antibiotics. Proportion of patients receiving appropriate initial antibiotic therapy was 94% overall. 18.6% patients were defined as "Immunosuppressed". No significant differences in baseline characteristics between groups

Exclusions: transfers to host institution because of lack of capacity at external institutions


Interventions154 patients randomised to discontinuation group; one of investigators recommended discontinuation of antibiotics to treating physician on weekdays if: non-infectious cause for radiographic infiltrates identified, signs and symptoms of active infection had resolved (in terms of temperature, white cell count, radiographic appearance, sputum characteristics and PaO2/ FiO2 ratio). 148 patients were randomised to the control group. Recommendations regarding choice of antibiotic therapy were made to both groups


OutcomesReported outcome measures:

  • Duration of antibiotic therapy for VAP
  • ITU mortality
  • Hospital mortality
  • Duration of ITU stay
  • Duration of hospital stay
  • Duration of mechanical ventilation
  • VAP recurrence during same ITU stay


NotesOutcome data was missing for 4 patients in the intervention group, and for 8 patients in the control group. Among intervention group, recommendations to discontinue antibiotics were given to the physicians of 142 patients (94.7%); among 88.7% of these patients antibiotics were discontinued within 48 hours of the recommendation. Trial author contacted, but no further information available


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskNo details provided

Allocation concealment (selection bias)Unclear riskNo details provided

Blinding (performance bias and detection bias)
All outcomes
High riskIntervention involved investigators contacting the physician team

Incomplete outcome data (attrition bias)
All outcomes
High riskOutcome data missing in 12/302 (4%) cases; no information given regarding missing outcome data

Selective reporting (reporting bias)Unclear riskUnclear

Other biasLow riskThere do not appear to be other major potential sources of bias

Pontet 2007

Methods4-centre Uruguayan study, conducted December 2005 to April 2006; 2 of these centres also recruited to the study Medina 2007, but outside this time period. Unblinded, randomised controlled study comparing PCT-guided strategy for antibiotic cessation versus standard therapy for VAP


Participants81 adult patients (medical, surgical, cardiothoracic and neurosurgical; mean age 54 years, 63% male; NF-GNB 23.4%; MRSA 6.1%; Day 1 MODS 6.2; Day 1 SOFA score 4.8) with suspected VAP. VAP was diagnosed on the basis of: new and persistent radiographic infiltrates, 2 of temperature ≥ 38.5 ºC or < 36 ºC, leukocytes ≥12,000/ mm3 or ≤ 4 x103/ mm3, and BAL culture ≥ 104 cfu/ml, or positive ETA plus CPIS > 6, or micro-organism in ≥ 2 blood cultures with identical sensitivity to tracheal secretions and in absence of other possible infection, or positive culture of pleural fluid. Patients were excluded on the basis of: AIDS, leukaemia or immunosuppression. A further 14 patients were excluded after randomisation; from control group, 5 patients were excluded because of short duration of treatment (3 patients) or negative BAL (3 patients); from the PCT group, 9 patients were excluded post-randomisation because Day 1 or 2 PCT was < 0.5 ng/mL. There were no significant baseline differences between groups in terms of demographics, underlying disease or prior antibiotic administration


InterventionsIntervention: for the group receiving PCT-guided therapy; if at day 7 PCT was < 0.5 ng/ml, antibiotic discontinuation was encouraged. Duration of therapy in control group was according to pre-existing guidelines in place at each ICU. Choice of antibiotic therapy was that of the treating physician. Most commonly used antibiotics were: cephalosporins, ampicillin-sulbactam and amikacin; antibiotic combinations were used in 54.5% cases


OutcomesData are presented as a per-protocol analysis. The following outcome measures were reported:

  • ITU mortality
  • VAP-related ITU mortality
  • Duration of mechanical ventilation
  • Duration of ITU stay
  • Non-resolution (therapeutic failure)
  • Relapse (Day 29)
  • Super-infection (Day 29)
  • Clinical resolution
  • CPIS (Day 1, 7)
  • MODS (Day 1, 7)
  • SOFA score (Day 1, 7)


NotesAll patients in the procalcitonin group completed at least 7 days of antibiotic therapy. At Day 7, antibiotics were discontinued for all patients with procalcitonin < 0.5 ng/ml


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Low riskBlock randomisation using random number table

Allocation concealment (selection bias)Low riskSealed, numbered envelopes opened in sequence

Blinding (performance bias and detection bias)
All outcomes
High riskTreating team were made aware of assignment on Day 7, when PCT measured and communicated to PCT group

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo patients lost to follow-up

Selective reporting (reporting bias)Unclear riskUnclear

Other biasHigh riskPotential source of bias as this is a per-protocol analysis; exclusion of 9 patients with low PCT measurements in the PCT group may exclude a higher proportion of relatively well patients compared with the control group

Singh 2000

MethodsSingle-centre study from the USA. Randomised controlled trial comparing strategy of 3 days' ciprofloxacin monotherapy versus standard therapy (duration and antibiotic choice at the discretion of physician) for patients with pulmonary infiltrates but low-probability pneumonia


ParticipantsStudy entry criteria: new-onset pulmonary infiltrate associated with possible nosocomial pneumonia. Modified Clinical Pulmonary Infection Score (CPIS) < 7 on Day 1 (suggesting low probability pneumonia)

81 adult medical and surgical ICU patients; 47 (58%) receiving mechanical ventilation; mean age 66.7 years; no data on sex. APACHE III score 41.8; mean CPIS 4.9. Prior mean duration of ICU stay 8.8 days and duration of mechanical ventilation 7.6 days. Chronic obstructive airways disease present in 27% cases. 5% patients were transplant recipients. With the exception of abnormal respiration (92% experimental group versus 71% standard-therapy group, P = 0.016), there were no significant differences in baseline characteristics between the 2 groups

Exclusions: HIV, chemotherapy-induced neutropenia, concurrent antibiotic administration (other than surgical prophylaxis), flouroquinolone allergy


InterventionsRandomised at Day 1 of episode of possible pneumonia. Intervention group (N = 39): 3 days' ciprofloxacin monotherapy. At Day 3 if CPIS < 7, antibiotics would be discontinued; if CPIS > 6, therapy would be continued, with choice of agent and duration of therapy at the discretion of treating physician, and incorporating microbiology results

Standard therapy (N = 42): choice and duration of antibiotic therapy at choice of treating physician


OutcomesThe following outcomes were reported:

  • Mortality (Day 3, 14, 30)
  • Duration of ITU stay
  • Emergence of antimicrobial resistance or superinfection (Day 28)
  • Duration of antibiotic therapy
  • Antimicrobial therapy cost


NotesPathogens associated with possible HAP were incompletely presented

For patients allocated to the short-course therapy, 0 patients with CPIS < 7 at Day 3 had antibiotics continued beyond 72 hours

A significant decrease in duration of therapy in "Standard therapy" group was observed with time (P = 0.0001), thought to be a result of unblinded nature of study. The study was terminated by institutional review board as it was deemed "unethical to continue study."


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear riskRandomisation process not described

Allocation concealment (selection bias)Unclear riskRandomisation/concealment not described

Blinding (performance bias and detection bias)
All outcomes
High riskThis was an unblinded study

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo missing outcome data

Selective reporting (reporting bias)High riskThe components of the composite measure of "emergence of antimicrobial resistance or superinfection" are not reported

Other biasHigh riskStopped early by institutional review board. Results for patients managed in "experimental" group appear to have influenced management of patients subsequently allocated to "standard therapy group"

Stolz 2009a

MethodsThe ProVAP study, an international, multi-centre study involving 7 ICUs in USA and Switzerland. Unblinded, randomised controlled trial comparing strategy utilising serum procalcitonin measurement to guide discontinuation of antibiotics for ICU patients with VAP, with antibiotic administration according to an agreed guideline


Participants101 patients with VAP; 36% NF-GNB; 10% MRSA; mean age 56; 75% male; 27% surgical patients; 19% with chronic obstructive airways disease. Mean SAPS II score 43; ODIN score 2.1; SOFA score 7.8. Mean duration of mechanical ventilation before onset of VAP 6 days. 75% received antibiotics during the 14 days before VAP. 89% patients had CPIS ≥ 6.ODIN score was slightly higher in the control group than the procalcitonin group (2.3 versus 1.9; P = 0.042); otherwise, there were no significant differences in baseline characteristics. VAP diagnosed according to clinical criteria: new or persistent infiltrates on chest radiography with at least 2 of purulent tracheal secretions, temperature > 38 ºC, leukocyte count > 11,000/ µL or < 3000/ µL; microbiological confirmation was not an essential criterion, and indeed was absent in 27% patients. Exclusions: treatment with immunosuppressants or long-term corticosteroid treatment; or underlying immunosuppressant disorder; co-existing extrapulmonary infection


Interventions101 patients were randomised on day of diagnosis of VAP (Day 0). Serum procalcitonin levels were measured from Day 0 to Day 10 for all patients (including patients in the control group). For the 51 patients in the intervention group, discontinuation of antibiotic therapy was encouraged according to an algorithm 72 hours (Day 2) after randomisation if PCT was < 0.5 µg/L or had decreased to 20% or less of level on Day 0

For the 50 patients randomised to the control group, procalcitonin levels were withheld, and duration of therapy was determined by treating physician

In both intervention and control groups, choice of antibiotic therapy was that of the attending physician


OutcomesThe following outcome measures were reported:

  • Mortality (Day 28)
  • In-hospital mortality
  • Duration of antibiotic therapy
  • Antibiotic-free days (Day 28)
  • Mechanical ventilation-free days (Day 28)
  • Duration of hospital stay
  • Number of ITU-free days alive (Day 28)
  • Clinical features associated with respiratory infection
  • PaO2/ FiO2
  • SOFA score
  • ODIN score
  • CPIS


NotesIt is unclear how many patients were treated with antibiotics beyond the point at which discontinuation was advocated by the protocol


Risk of bias

BiasAuthors' judgementSupport for judgement

Random sequence generation (selection bias)Unclear risk"Arbitrary allocation to... treatment assignments based on sealed, opaque envelopes."

Allocation concealment (selection bias)Low risk"Treating physicians were not aware of envelope contents before randomisation."

Blinding (performance bias and detection bias)
All outcomes
High riskNot blinded

Incomplete outcome data (attrition bias)
All outcomes
Low riskNo patients lost to follow-up

Selective reporting (reporting bias)High riskComplete data on numbers of patients for whom physicians violate (PCT) protocol not presented

Other biasLow riskThere appear not to be other major potential sources of bias

 
Characteristics of excluded studies [ordered by study ID]

StudyReason for exclusion

Cai 2001A randomised controlled study investigating diagnostic strategies (quantitative versus qualitative culture of respiratory tract specimens) on outcome from VAP

CCCTG 2006This 2-by-2 factorial randomised controlled study aiming to compare: i. invasive and non-invasive diagnostic strategies for diagnosis of VAP, and ii. initial empiric treatment with meropenem or meropenem plus ciprofloxacin for suspected VAP. There was no significant difference in number of antibiotic-free days between groups of patients allocated to invasive or non-invasive strategies

Chastre 2003bData subsequently published in full (Chastre 2003a)

Fagon 2000This was a randomised study designed to compare strategies for diagnosis and selection of initial antimicrobial therapy of VAP, not duration of therapy. For groups of patients randomised to both invasive and non-invasive diagnostic strategies, recommended duration of therapy in the presence of positive respiratory culture (i.e. confirmed pneumonia) was 14 days

Hochreiter 2009This was a randomised controlled study comparing a strategy using serial procalcitonin (PCT) measurement to guide discontinuation of antibiotic therapy for treatment of sepsis in 110 surgical intensive care patients with standard therapy. Of these patients, 43 had "pneumonia"; it is unclear what proportion had nosocomial or community-acquired pneumonia, and what proportion of patients was receiving mechanical ventilation at time of diagnosis. Duration of antibiotic therapy was significantly shorter in the intervention (PCT-guided) group (5.9 +/- 1.7 days versus 7.9 +/- 0.5 days), but outcome data relevant to this systematic review are restricted to duration of ITU stay and hospital mortality

Ibrahim 2001Non-randomised before-and-after study investigating a clinical guideline regarding initial treatment and subsequent discontinuation of antibiotic therapy

Kim 2009This was an RCT investigating effectiveness of an antibiotic de-escalation protocol for patients with low probability of HAP (according to CPIS and culture results), published in abstract form only. It has not been possible to contact study authors for further details. It is unclear whether it was a single or multi-centre study. 109 patients (unclear whether exclusively adults or not) with HAP (diagnostic criteria not described) were randomised to the de-escalation protocol (N = 54) or standard therapy (N = 55). The protocol is not described nor relevant outcome data presented adequately for inclusion in this review. In addition, the significantly higher rate of appropriate initial antibiotic therapy in the de-escalation group represents a potential risk of bias

Kollef 2005Prospective observational study investigating application of previously described clinical guideline (Ibrahim 2001) for patients with suspected VAP, but negative quantitative BAL results

Maldonado-Ortiz 2004This multi-centre randomised controlled study from Mexico enrolled 65 patients in a study intended to evaluate a strategy of early discontinuation of empirical antibiotic therapy: it has been published in abstract form only. 31 patients were allocated to early (< 8 days) discontinuation of empirical therapy versus 34 patients to late discontinuation (> 9 days). Patient characteristics and diagnostic criteria were not described. Outcome data presented in the abstract was inadequate for the study's inclusion in this review, and contact with a trial author did not yield any further information. Furthermore, a highly significant risk of bias was identified: antibiotic discontinuation at Day 8 was higher (70.6%) among patients allocated to late discontinuation than among patients allocated to early discontinuation (67.7%)

Nobre 2008This was a randomised controlled study comparing a strategy using serial measurements of procalcitonin (PCT) to guide cessation of antibiotic therapy with standard therapy in critically ill patients with sepsis or septic shock. 79 patients were randomised, of whom a total of 47 patients had sepsis of pulmonary origin. A high proportion of patients (68%) had community-acquired sepsis. A significant proportion of patients in the PCT group (19%) had the protocol overridden to receive a longer course of antibiotics than advised by the algorithm. On intention-to-treat analysis, the difference in antibiotic days between control and intervention groups for all patients was not significant. A decision was made to exclude this study on the basis of small numbers of the subgroup of patients with suspected HAP or VAP and the lack of significant difference between groups in terms of duration of therapy

Peery 2001This was a randomised study comparing diagnostic strategies for suspected VAP. It was not designed to investigate duration of therapy; there were no protocols to guide duration of antibiotic therapy

Rello 2004This was an observational rather than a randomised controlled study. It investigated outcomes following introduction of a "De-escalation" strategy which incorporated the initial administration of broad spectrum antibiotics and subsequent simplification of antibiotic treatment with culture results: 1. changing to monotherapy in absence of Pseudomonas sp; 2. shortening therapy to < 5 days if culture negative and > 48 hours of defervescence; 3. changing from broad to narrow spectrum agent on basis of culture results

Sanchez-Nieto 1998A randomised clinical trial comparing the effects of an invasive quantitative diagnostic strategy versus a non-invasive strategy on management of and outcome from suspected VAP

Schroeder 2007This was a RCT comparing a procalcitonin-guided antibiotic discontinuation strategy with standard treatment for surgical intensive care patients with severe sepsis. The reasons for exclusion of this study are: 1. its very small size (of the 27 patients enrolled in this study, only 8 were diagnosed with pneumonia); 2. it is unclear what proportion of patients had nosocomial versus community-acquired infection; 3. of the patients with "pneumonia" it is unclear what proportion were receiving mechanical ventilation at time of diagnosis; 4. limited outcome data relevant to this systematic review are published (in-hospital mortality and duration of ICU stay)

Singh 1998Data subsequently published in full (Singh 2000)

Sole 2000A RCT to evaluate invasive versus non-invasive diagnostic methods on outcome from VAP

Stolz 2009bData subsequently published in full (Stolz 2009a)

Svoboda 2007RCT evaluating PCT-guided strategies in the management of septic illness after multiple trauma or major surgery. The study makes no reference to patients with HAP

Wolff 2003Data subsequently published in full (Chastre 2003a)

 
Characteristics of ongoing studies [ordered by study ID]
NCT00934011

Trial name or titleComparative study of C-reactive protein versus procalcitonin to guide antibiotic therapy in patients with severe sepsis and septic shock admitted to the Intensive Care Unit

MethodsRandomised controlled trial

ParticipantsAdult ICU patients with severe sepsis or septic shock

InterventionsCRP-guided antibiotic therapy versus procalcitonin-guided antibiotic therapy

OutcomesPrimary: duration of antibiotic therapy for first episode infection, total antibiotic days, 28-day antibiotic-free days

Starting dateSeptember 2009

Contact informationhttp://clinicaltrials.gov/ct2/show/NCT00934011

NotesNCT00934011

NCT00987818

Trial name or titleReduction of antibiotic use in the ICU: procalcitonin guided versus conventional antibiotic therapy in patients with sepsis in the ICU

MethodsRandomised controlled study

ParticipantsAdult ICU patients receiving antibiotic therapy for sepsis of suspected or proven focus of infection

InterventionsProcalcitonin-guided antibiotic therapy versus standard antibiotic therapy

OutcomesPrimary outcome: duration of antibiotic therapy; secondary outcome: 28-day mortality

Starting dateOctober 2009

Contact informationhttp://clinicaltrials.gov/ct2/show/NCT00987818

NotesNCT00987818

PASS

Trial name or titleThe procalcitonin and survival study (PASS)

MethodsA randomised multi-centre investigator-initiated trial to investigate whether procalcitonin-guided diagnostic and therapeutic strategies can improve survival in intensive care unit patients

Participants1000 critically ill patients

Interventions"Standard of care" versus "standard of care and procalcitonin-guided diagnostics and treatment of infection"

OutcomesPrimary outcome: 28-day mortality

Starting dateIn progress

Contact informationhttp://clinicaltrials.gov/ct2/show/NCT00271752

NotesNCT00271752

Pro-SEPS

Trial name or titleRandomised multicenter prospective study of procalcitonin-guided treatment on antibiotic use and outcome in severe sepsis ICU patients without obvious infection

MethodsRandomised controlled trial

ParticipantsAdult patients hospitalised in resuscitation ward, severe sepsis symptomatology, 2 or more SIRS criteria, at least one organ deficiency, no infectious aetiology

InterventionsDuration of antibiotic therapy guided by procalcitonin level versus standard care

OutcomesPrimary outcome: antibiotic treatment at day 5

Starting dateDecember 2007

Contact informationhttp://clinicaltrials.gov/ct2/show/NCT01025180

NotesNCT01025180

SAPS

Trial name or titleSafety and efficacy of procalcitonin guided antibiotic therapy in adult intensive care units (ICU's) (SAPS)

MethodsRandomised controlled trial

ParticipantsAdult ICU patients with suspected or proven infection

InterventionsProcalcitonin-guided antibiotic therapy versus standard therapy

OutcomesPrimary: 28-day mortality; consumption of antibiotics expressed as the defined daily dosage and duration of antibiotic therapy expressed in days of therapy

Starting dateNovember 2009

Contact informationhttp://clinicaltrials.gov/ct2/show/NCT01139489

NotesNCT01139489

SISPCT

Trial name or titlePlacebo-controlled trial of sodium selenite and procalcitonin guided antimicrobial therapy in severe sepsis (SISPCT)

MethodsProspective, randomised multi-centre 2 x 2 trial

ParticipantsAdult patients with severe sepsis or septic shock, with onset of < 24 hours

Interventions2 x 2 trial:

1. Intravenous sodium-selenite versus placebo

2. Procalcitonin-guided antibiotic therapy versus alternative (non-PCT guided) antibiotic protocol

OutcomesPrimary outcome: 28-day mortality

Starting dateNovember 2009

Contact informationwww.clinicaltrials.gov/ct2/show/NCT00832039

NotesNCT00832039

 
Comparison 1. Short (fixed)-course antibiotic therapy versus prolonged-course antibiotic therapy for HAP

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 28-day mortality2431Odds Ratio (M-H, Random, 95% CI)1.08 [0.66, 1.76]

    1.1 NF-GNB
1127Odds Ratio (M-H, Random, 95% CI)0.71 [0.32, 1.56]

    1.2 MRSA
142Odds Ratio (M-H, Random, 95% CI)1.28 [0.32, 5.09]

    1.3 Non NF-GNB/MRSA
1232Odds Ratio (M-H, Random, 95% CI)1.65 [0.73, 3.73]

    1.4 Unspecified organism
130Odds Ratio (M-H, Random, 95% CI)0.93 [0.21, 4.11]

 2 Recurrence of pneumonia3508Odds Ratio (M-H, Random, 95% CI)1.37 [0.87, 2.17]

    2.1 NF-GNB
2176Odds Ratio (M-H, Random, 95% CI)2.18 [1.14, 4.16]

    2.2 MRSA
249Odds Ratio (M-H, Random, 95% CI)1.56 [0.12, 19.61]

    2.3 Non NF-GNB/MRSA
2253Odds Ratio (M-H, Random, 95% CI)0.98 [0.55, 1.78]

    2.4 Unspecified organism
130Odds Ratio (M-H, Random, 95% CI)1.17 [0.14, 9.59]

 3 28-day antibiotic-free days2431Mean Difference (IV, Random, 95% CI)4.02 [2.26, 5.78]

    3.1 NF-GNB
1127Mean Difference (IV, Random, 95% CI)4.5 [2.25, 6.75]

    3.2 MRSA
142Mean Difference (IV, Random, 95% CI)8.0 [4.14, 11.86]

    3.3 Non NF-GNB/ MRSA
1232Mean Difference (IV, Random, 95% CI)3.70 [2.09, 5.31]

    3.4 Unspecified organism
130Mean Difference (IV, Random, 95% CI)2.3 [1.03, 3.57]

 4 ITU mortality2107Odds Ratio (M-H, Random, 95% CI)0.85 [0.37, 1.91]

 5 Non-resolution of pneumonia177Odds Ratio (M-H, Fixed, 95% CI)1.80 [0.65, 5.02]

    5.1 NF-GNB
149Odds Ratio (M-H, Fixed, 95% CI)1.89 [0.49, 7.40]

    5.2 MRSA
17Odds Ratio (M-H, Fixed, 95% CI)11.0 [0.28, 433.80]

    5.3 Non NF-GNB/MRSA
121Odds Ratio (M-H, Fixed, 95% CI)1.0 [0.16, 6.25]

 6 In-hospital mortality1401Odds Ratio (M-H, Fixed, 95% CI)1.09 [0.71, 1.67]

    6.1 NF-GNB
1127Odds Ratio (M-H, Fixed, 95% CI)0.75 [0.36, 1.53]

    6.2 MRSA
142Odds Ratio (M-H, Fixed, 95% CI)1.47 [0.43, 4.95]

    6.3 Non NF-GNB/MRSA
1232Odds Ratio (M-H, Fixed, 95% CI)1.32 [0.72, 2.42]

 7 Recurrence due to multi-resistant organism1110Odds Ratio (M-H, Fixed, 95% CI)0.44 [0.21, 0.95]

 8 Duration of ITU stay2431Mean Difference (IV, Random, 95% CI)-0.01 [-2.30, 2.27]

    8.1 NF-GNB
1127Mean Difference (IV, Random, 95% CI)0.90 [-5.40, 7.20]

    8.2 MRSA
142Mean Difference (IV, Random, 95% CI)2.90 [-8.39, 14.19]

    8.3 Non NF-GNB/MRSA
1232Mean Difference (IV, Random, 95% CI)2.70 [-1.88, 7.28]

    8.4 Unspecified organism
130Mean Difference (IV, Random, 95% CI)-1.60 [-4.61, 1.41]

 9 Duration of hospital stay130Mean Difference (IV, Fixed, 95% CI)-1.0 [-4.11, 2.11]

 10 Duration of mechanical ventilation2107Mean Difference (IV, Random, 95% CI)-0.01 [-0.57, 0.55]

 11 28-day mechanical ventilation-free days2431Mean Difference (IV, Random, 95% CI)0.47 [-0.97, 1.92]

    11.1 NF-GNB
1127Mean Difference (IV, Random, 95% CI)1.50 [-1.77, 4.77]

    11.2 MRSA
142Mean Difference (IV, Random, 95% CI)-1.30 [-6.37, 3.77]

    11.3 Non NF-GNB/MRSA
1232Mean Difference (IV, Random, 95% CI)-1.20 [-3.54, 1.14]

    11.4 Unspecified organism
130Mean Difference (IV, Random, 95% CI)1.30 [-0.03, 2.63]

 12 Mortality associated with VAP177Mean Difference (IV, Fixed, 95% CI)1.0 [-8.85, 10.85]

 
Comparison 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 30-day mortality181Odds Ratio (M-H, Fixed, 95% CI)0.33 [0.10, 1.03]

 2 Episodes of superinfection or antimicrobial resistance181Odds Ratio (M-H, Fixed, 95% CI)0.29 [0.09, 0.92]

 3 Duration of antibiotic therapy181Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 4 Duration of ITU stay181Mean Difference (IV, Fixed, 95% CI)0.0 [0.0, 0.0]

 
Comparison 3. Discontinuation of antibiotics according clinical guideline

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 Recurrence of pneumonia1290Odds Ratio (M-H, Fixed, 95% CI)0.88 [0.48, 1.59]

 2 Duration of antibiotic therapy1290Mean Difference (IV, Fixed, 95% CI)-2.0 [-3.21, -0.79]

 3 In-hospital mortality1290Odds Ratio (M-H, Fixed, 95% CI)0.80 [0.49, 1.29]

 4 Duration of ITU stay1290Mean Difference (IV, Fixed, 95% CI)-0.20 [-1.75, 1.35]

 5 Duration of hospital stay1290Mean Difference (IV, Fixed, 95% CI)0.30 [-3.63, 4.23]

 6 Duration of mechanical ventilation1290Mean Difference (IV, Fixed, 95% CI)-0.30 [-1.79, 1.19]

 
Comparison 4. Discontinuation of antibiotic therapy according to serum procalcitonin level

Outcome or subgroup titleNo. of studiesNo. of participantsStatistical methodEffect size

 1 28-day mortality3308Odds Ratio (M-H, Random, 95% CI)0.66 [0.39, 1.14]

 2 Recurrence of pneumonia166Odds Ratio (M-H, Fixed, 95% CI)2.06 [0.74, 5.70]

 3 28-day antibiotic-free days3308Mean Difference (IV, Random, 95% CI)2.80 [1.39, 4.21]

 4 Duration of antibiotic therapy3308Mean Difference (IV, Random, 95% CI)-3.20 [-4.45, -1.95]

 5 In-hospital mortality1101Odds Ratio (M-H, Fixed, 95% CI)0.63 [0.25, 1.58]

 6 ITU mortality166Odds Ratio (M-H, Fixed, 95% CI)0.76 [0.26, 2.22]

 7 Non-resolution of pneumonia166Odds Ratio (M-H, Fixed, 95% CI)1.17 [0.38, 3.62]

 8 Recurrence due to resistant organism166Odds Ratio (M-H, Fixed, 95% CI)1.75 [0.49, 6.21]

 9 ITU duration of stay2167Mean Difference (IV, Random, 95% CI)-2.68 [-6.01, 0.66]

 10 Duration of hospital stay1101Mean Difference (IV, Fixed, 95% CI)-2.40 [-6.40, 1.60]

 11 Duration of mechanical ventilation2167Mean Difference (IV, Random, 95% CI)-0.35 [-3.24, 2.54]

 
Summary of findings for the main comparison. Should short (fixed duration)-course antibiotic therapy versus prolonged-course antibiotic therapy be used for critically ill patients with hospital-acquired pneumonia?

Should short (fixed duration)-course antibiotic therapy versus prolonged-course antibiotic therapy be used for critically ill patients with hospital-acquired pneumonia?

Patient or population: critically ill patients with hospital-acquired pneumonia
Settings: ICU
Intervention: short (fixed duration)-course antibiotic therapy
Comparison: prolonged course antibiotic therapy

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

Prolonged-course antibiotic therapyShort (fixed duration)-course antibiotic therapy

28-day mortalityStudy populationOR 1.08
(0.66 to 1.76)
431
(2 studies)

186 per 1000198 per 1000
(131 to 287)

Medium-risk population

270 per 1000285 per 1000
(196 to 394)

28-day mortality - NF-GNBStudy populationOR 0.71
(0.32 to 1.56)
127
(1 study)
See comment

302 per 1000235 per 1000
(122 to 403)

Medium-risk population

302 per 1000235 per 1000
(122 to 403)

28-day mortality - MRSAStudy populationOR 1.28
(0.32 to 5.09)
42
(1 study)
See comment

238 per 1000286 per 1000
(91 to 614)

Medium-risk population

238 per 1000286 per 1000
(91 to 614)

Recurrence of pneumoniaStudy populationOR 1.37
(0.87 to 2.17)
508
(3 studies)

245 per 1000308 per 1000
(220 to 413)

Medium-risk population

227 per 1000287 per 1000
(203 to 389)

Recurrence of pneumonia - NF-GNBStudy populationOR 2.18
(1.14 to 4.16)
176
(2 studies)

247 per 1000417 per 1000
(272 to 577)

Medium-risk population

241 per 1000409 per 1000
(266 to 569)

Recurrence of pneumonia - MRSAStudy populationOR 1.56
(0.12 to 19.61)
49
(2 studies)

370 per 1000478 per 1000
(66 to 920)

Medium-risk population

298 per 1000398 per 1000
(48 to 893)

28-day antibiotic-free daysThe mean 28-day antibiotic-free days in the intervention groups was
4.02 higher
(2.26 to 5.78 higher)
431
(2 studies)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; MRSA: methicillin-resistant Staphylococcus aureus; NF-GNB: non-fermenting Gram-negative bacilli; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 
Summary of findings 2. Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital-acquired pneumonia

Discontinuation of antibiotics according to Clinical Pulmonary Infection Score for critically ill adults with hospital-acquired pneumonia

Patient or population: critically ill adults with hospital-acquired pneumonia
Settings: ICU
Intervention: discontinuation of antibiotics according to Clinical Pulmonary Infection Score

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlDiscontinuation of antibiotics according to Clinical Pulmonary Infection Score

30-day mortalityStudy populationOR 0.33
(0.1 to 1.03)
81
(1 study)
See comment

310 per 1000129 per 1000
(43 to 316)

Medium-risk population

310 per 1000129 per 1000
(43 to 316)

Episodes of superinfection or antimicrobial resistanceStudy populationOR 0.29
(0.09 to 0.92)
81
(1 study)
See comment

333 per 1000126 per 1000
(43 to 315)

Medium-risk population

333 per 1000126 per 1000
(43 to 315)

Duration of antibiotic therapySee commentSee commentNot estimable81
(1 study)
See comment

Duration of ITU staySee commentSee commentNot estimable81
(1 study)
See comment

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ITU: intensive therapy unit; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 
Summary of findings 3. Discontinuation of antibiotics according to clinical guideline for hospital-acquired pneumonia in critically ill adults

Discontinuation of antibiotics according to clinical guideline for hospital-acquired pneumonia in critically ill adults

Patient or population: patients with hospital-acquired pneumonia in critically ill adults
Settings: ICU
Intervention: discontinuation of antibiotics according to clinical guideline

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlDiscontinuation of antibiotics according to clinical guideline

Recurrence of pneumoniaStudy populationOR 0.88
(0.48 to 1.59)
290
(1)
See comment

193 per 1000174 per 1000
(103 to 275)

Medium-risk population

193 per 1000174 per 1000
(103 to 275)

Duration of antibiotic therapyThe mean duration of antibiotic therapy in the intervention groups was
2 lower
(3.21 to 0.79 lower)
290
(1)
See comment

In-hospital mortalityStudy populationOR 0.8
(0.49 to 1.29)
290
(1)
See comment

371 per 1000321 per 1000
(224 to 432)

Medium-risk population

371 per 1000321 per 1000
(224 to 432)

Duration of ICU stayThe mean duration of ICU stay in the intervention groups was
0.2 lower
(1.75 lower to 1.35 higher)
290
(1)
See comment

Duration of hospital stayThe mean duration of hospital stay in the intervention groups was
0.3 higher
(3.63 lower to 4.23 higher)
290
(1)
See comment

Duration of mechanical ventilationThe mean duration of mechanical ventilation in the intervention groups was
0.3 lower
(1.79 lower to 1.19 higher)
290
(1)
See comment

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ICU: intensive care unit; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.

 
Summary of findings 4. Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital-acquired pneumonia in critically ill adults

Discontinuation of antibiotic therapy according to serum procalcitonin level for hospital-acquired pneumonia in critically ill adults

Patient or population: hospital-acquired pneumonia in critically ill adults
Settings: ICU
Intervention: discontinuation of antibiotic therapy according to serum procalcitonin level

OutcomesIllustrative comparative risks* (95% CI)Relative effect
(95% CI)
No of participants
(studies)
Quality of the evidence
(GRADE)
Comments

Assumed riskCorresponding risk

ControlDiscontinuation of antibiotic therapy according to serum procalcitonin level

28-day mortalityStudy populationOR 0.66
(0.39 to 1.14)
308
(3 studies)

265 per 1000192 per 1000
(123 to 291)

Medium-risk population

258 per 1000187 per 1000
(119 to 284)

Recurrence of pneumoniaStudy populationOR 2.06
(0.74 to 5.7)
66
(1 study)
See comment

286 per 1000452 per 1000
(229 to 695)

Medium-risk population

286 per 1000452 per 1000
(229 to 695)

28-day antibiotic-free daysThe mean 28-day antibiotic-free days in the intervention groups was
2.8 higher
(1.39 to 4.21 higher)
167
(2 studies)

Duration of antibiotic therapy
days
The mean duration of antibiotic therapy in the intervention groups was
3.2 lower
(4.45 to 1.95 lower)
308
(3 studies)

*The basis for the assumed risk (e.g. the median control group risk across studies) is provided in footnotes. The corresponding risk (and its 95% confidence interval) is based on the assumed risk in the comparison group and the relative effect of the intervention (and its 95% CI).
CI: confidence interval; ICU: intensive care unit; OR: odds ratio

GRADE Working Group grades of evidence
High quality: Further research is very unlikely to change our confidence in the estimate of effect.
Moderate quality: Further research is likely to have an important impact on our confidence in the estimate of effect and may change the estimate.
Low quality: Further research is very likely to have an important impact on our confidence in the estimate of effect and is likely to change the estimate.
Very low quality: We are very uncertain about the estimate.