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

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Abstract

Background

Pneumonia is the most common hospital‐acquired infection affecting patients in the intensive care unit (ICU). However, the optimal duration of antibiotic therapy for hospital‐acquired pneumonia (HAP) is uncertain.

Objectives

To assess the effectiveness of short versus prolonged‐course antibiotic administration for HAP in critically ill adults, including patients with ventilator‐associated pneumonia (VAP).

Search methods

We searched the Cochrane Central Register of Controlled Trials (CENTRAL) (The Cochrane Library 2011, Issue 1), which includes the Cochrane Acute Respiratory Infections Group's Specialised Register, MEDLINE (1950 to February week 4, 2011), EMBASE (1974 to March 2011), LILACS (1985 to March 2011) and Web of Science (1985 to March 2011).

Selection criteria

We considered all randomised controlled trials (RCTs) comparing fixed durations of antibiotic therapy, or comparing a protocol intended to limit duration of therapy with standard care, for HAP (including patients with VAP) in critically ill adults.

Data collection and analysis

Two review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information.

Main results

Eight studies (1703 patients) were included. Methodology varied considerably and we found little evidence regarding patients with a high probability of HAP who were not mechanically ventilated. For patients with VAP, a short seven to eight‐day course of antibiotics compared with a prolonged 10 to 15‐day course (three studies, N = 508) increased 28‐day antibiotic‐free days (mean difference (MD) 4.02; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi‐resistant organisms (odds ratio (OR) 0.44; 95% CI 0.21 to 0.95), without adversely affecting other outcomes. However, for cases of VAP due to non‐fermenting Gram‐negative bacilli (NF‐GNB), recurrence was greater after short‐course therapy (OR 2.18; 95% CI 1.14 to 4.16; two studies, N = 176), though other outcome measures did not significantly differ. Discontinuation strategies utilising clinical features (one study; N = 302) or procalcitonin (three studies; N = 323) led to a reduction in duration of therapy and, in the procalcitonin studies, increased 28‐day antibiotic‐free days (MD 2.80; 95% CI 1.39 to 4.21) without negatively affecting other outcomes.

Authors' conclusions

We conclude that for patients with VAP not due to NF‐GNB, a short fixed‐course (seven or eight days) antibiotic therapy may be more appropriate than a prolonged course (10 to 15 days). Use of an individualised strategy (incorporating clinical features or serum procalcitonin) appears to safely reduce duration of antibiotic therapy for VAP.

PICOs

Population
Intervention
Comparison
Outcome

The PICO model is widely used and taught in evidence-based health care as a strategy for formulating questions and search strategies and for characterizing clinical studies or meta-analyses. PICO stands for four different potential components of a clinical question: Patient, Population or Problem; Intervention; Comparison; Outcome.

See more on using PICO in the Cochrane Handbook.

Plain language summary

A review of strategies intended to limit duration of antibiotic therapy for hospital‐acquired pneumonia in intensive care unit patients

Hospital‐acquired pneumonia (HAP) is the major cause of hospital‐acquired infection in the intensive care unit (ICU). There are a number of factors which predispose the critically ill to developing pneumonia, among which the most important may be tracheal intubation to enable mechanical ventilation; indeed, the majority of ICU patients with HAP have what is termed ventilator‐associated pneumonia (VAP).

There is concern that unnecessary prolongation of antibiotic therapy may lead to the patient acquiring antibiotic‐resistant organisms, which may be more difficult to treat when they cause infection, and will increase pharmacy costs. On the other hand, too short a course of therapy risks the treatment failing.

We aimed to evaluate the evidence from randomised controlled trials (RCTs) comparing a short with a long course of antibiotics, or comparing a protocol that aimed to shorten the course of antibiotics with standard care, for ICU patients with HAP (including those with VAP).

The eight RCTs (involving 1703 patients) we identified applied diverse methodological approaches to patient populations which differed substantially, limiting opportunities for combining data in a meta‐analysis. Furthermore, we found very few data regarding duration of antibiotic therapy for ICU patients who have HAP, but are not mechanically ventilated. However, for patients with VAP, a course of seven or eight days of antibiotics was associated with an overall decrease in antibiotic administration and reduced the recurrence of pneumonia due to resistant organisms when compared with a 10 to 15‐day course. Nevertheless, in cases when the VAP was due to a particular type of organism ('non‐fermenting Gram‐negative bacilli') which can be difficult to eradicate with antibiotics, the risk of pneumonia recurring appeared higher after a short course of antibiotics.

Lastly, some studies indicated that having an individualised stop‐point for antibiotics (for example, clinical features, such as temperature, or results of a blood test) was associated with a shorter course of treatment and reduction in overall antibiotic exposure without negatively affecting other outcomes.