Abstract: We included 12 studies with 3571 participants. All included studies examined the empiric use of one antimicrobial regimen versus another for the treatment of adults with VAP, but the particular drug regimens examined by each study varied. There was potential for bias because some studies did not report outcomes for all participants. All but one study reported sources of funding or author affiliations with pharmaceutical companies. We found no statistical difference in all-cause mortality between monotherapy and combination therapy (N = 4; odds ratio (OR) monotherapy versus combination 0.97, 95% confidence interval (CI) 0.73 to 1.30), clinical cure (N = 2; OR monotherapy versus combination 0.88, 95% CI 0.56 to 1.36), length of stay in ICU (mean difference (MD) 0.65, 95% CI 0.07 to 1.23) or adverse events (N = 2; OR monotherapy versus combination 0.93, 95% CI 0.68 to 1.26). We downgraded the quality of evidence for all-cause mortality, adverse events, and length of ICU stay to moderate for this comparison. We determined clinical cure for this comparison to be of very low-quality evidence. For our second comparison of combination therapy with optional adjunctives only one meta-analysis could be performed due to a lack of trials comparing the same antibiotic regimens. Two studies compared tigecycline versus imipenem-cilastatin for clinical cure in the clinically evaluable population and there was a statistically significant increase in clinical cure for imipenem-cilastatin (N = 2; OR tigecycline versus imipenem-cilastatin 0.44, 95% CI 0.23 to 0.84). Of importance, this effect was due to a single study. We found no statistical difference in all-cause mortality between carbapenem and non-carbapenem therapies (N = 1; OR carbapenem versus non-carbapenem 0.59, 95% CI 0.30 to 1.19) or adverse events (N = 3; OR carbapenem versus non-carbapenem 0.78, 95% CI 0.56 to 1.09), but we found that carbapenems are associated with a statistically significant increase in the clinical cure (N = 3; OR carbapenem versus non-carbapenem 1.53, 95% CI 1.11 to 2.12 for intention-to-treat (ITT) analysis and N = 2; OR carbapenem versus non-carbapenem 2.29, 95% CI 1.19 to 4.43 for clinically evaluable patients analysis). For this comparison we downgraded the quality of evidence for mortality, and clinical cure (ITT and clinically evaluable populations) to moderate. We determined the quality of evidence for adverse events to be low. We did not find a difference between monotherapy and combination therapy for the treatment of people with VAP. Since studies did not identify patients with increased risk for multidrug-resistant bacteria, these data may not be generalisable to all patient groups. However, this is the largest meta-analysis comparing monotherapy to multiple antibiotic therapies for VAP and contributes further evidence to the safety of using effective monotherapy for the empiric treatment of VAP. Due to lack of studies, we could not evaluate the best antibiotic choice for VAP, but carbapenems as a class may result in better clinical cure than other tested antibiotics.

Plain-language summary: We looked at studies involving adults aged over 18 years who were treated in intensive care units for ventilator-associated pneumonia and needed antibiotic treatment. We analysed 12 studies with 3571 participants. All included studies looked at the use of one antibiotic treatment plan versus another, but these varied among studies. There was potential for bias because some studies did not report outcomes for all participants, and funding for many was provided by pharmaceutical companies and study authors were affiliated with these companies. We used statistical techniques to evaluate our results. For single versus multiple antibiotics, we found no difference in rates of death or cure, or adverse events. For our comparison of combination therapies with optional adjunctives we were only able to analyse clinical cure for one the antibiotics Tigecycline and imipenem-cilastatin for which imipenem-cilastatin was found to have higher clinica cure. We also looked at carbapenem (antibiotics used to treat infections caused by multidrug-resistant bacteria) versus non-carbapenem treatment; we found no difference in death rate or adverse effects, but we found that carbapenems are associated with an increase in clinical cure. We assessed evidence quality as moderate for most outcomes, and very low for clinical cure when single-antibiotic treatment was compared with multiple antibiotic therapy. We also found that evidence quality was low for adverse events when carbapenem was compared with non-carbapenem treatment. We did not find differences between single and combination therapy, lending support to use of a single-antibiotic treatment plan for people with ventilator-associated pneumonia. This may not be applicable to all patients because studies did not identify patients who are at risk of exposure to harmful types of bacteria. We could not evaluate the best single-antibiotic choice to treat people with ventilator-associated pneumonia because there were too few studies, but carbapenems may achieve better cure rates than other tested antibiotics.