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

Abstract

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. To assess the effectiveness of short versus prolonged-course antibiotic administration for HAP in critically ill adults, including patients with ventilator-associated pneumonia (VAP). 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). 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. Two review authors conducted data extraction and assessment of risk of bias. We contacted trial authors for additional information. 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 (odds ratio (OR) 4.02; 95% confidence interval (CI) 2.26 to 5.78) and reduced recurrence of VAP due to multi-resistant organisms (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 (mean difference (MD) 2.80; 95% CI 1.39 to 4.21) without negatively affecting other outcomes. 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.