Carbapenems vs. alternative β-lactams for the treatment of nosocomial pneumonia: A systematic review and meta-analysis

Background: Carbapenems have shown efficacy in treating nosocomial pneumonias in clinical trials despite a reported low lung penetration compared with other beta-lactams. Preserving the clinical activity of carbapenems through stewardship efforts is essential. The aim of this review was to identify any differences in outcomes potentially as a function of decreased penetration. Methods: PubMed and the Cochrane Library were systematically searched for clinical trials comparing carbapenems with other anti-pseudomonal beta-lactams for treatment of nosocomial pneumonia through to end December 2016. Trials reporting clinical and microbiological outcomes associated with treatment were included. Pediatric studies and those with uneven comparators (e.g., carbapenem vs. combination Gram-negative therapy) were excluded. Fixed effects models were used to evaluate the impact of treatment on the odds of clinical failure, death, or microbiological failure. Results: 252 unique articles were identified; five met inclusion criteria and comprised 640 patients in the carbapenem group and 634 patients in the beta-lactam group. No differences in clinical failure (odds ratio [OR] 1.08, 95% confidence interval [CI] [0.81-1.44], I-2 = 16%) or mortality (OR 0.75, CI 0.57-1.11, I-2 = 0%) were noted between groups. Patients infected with P. aeruginosa and treated with imipenem were more likely to experience clinical failure (OR 4.21, CI 1.51-11.12,I-2 = 44%) and to develop resistance to the study carbapenem (OR 2.86, CI 1.08-6.44, I-2 = 13%) than those treated with alternative beta-lactams. Conclusions: No differences in clinical outcomes were observed between carbapenems and noncarbapenem beta-lactams in nosocomial pneumonias. Those infected with P. aeruginosa fared worse and were more likely to have resistance develop if they were treated with imipenem. Additional studies are warranted. (c) 2018 Elsevier B.V. and International Society of Chemotherapy. All rights reserved.