Carbapenems versus alternative β-lactams monotherapy or in combination for febrile neutropenia Systematic review and meta-analysis of randomized controlled trial

Background: Febrile neutropenia (FN) in cancer patients can be life threatening and require the timely antimicrobial agents treatment. Methods: To compare the effectiveness and safety of carbapenems versus beta-lactams for FN. PubMed, Medline (Ovid SP), Cochrane CENTRAL, and Embase were searched up to March 2019. FN in patients due to undergoing chemotherapy and treated with carbapenems and beta-lactams were included. Odds ratio (OR) and 95% confidence interval (CI) were estimated. Results: Fifty randomized controlled trials (RCTs) studies involving 10,995 participants were included. Carbapenems were more likely to experience treatment success without modification (OR = 1.34, 95% CI = 1.24-1.46) compared with beta-lactams. Meropenem (OR = 1.36, 95% CI = 1.18-1.56; OR = 1.24, 95% CI = 1.01-1.53), imipenem/cilastatin (OR = 1.40, 95% CI = 1.19-1.65; OR = 1.31, 95% CI = 1.04-1.67) showed higher effectiveness from that by beta-lactams monotherapy or in combination with aminoglycoside, respectively. Carbapenems-aminoglycoside combination therapy does not provide an advantage over carbapenems alone. Meropenem showed similar risk of adverse events (AEs) versus beta-lactams. Imipenem/cilastatin was related to higher risk of AEs compared with beta-lactams. There was no significant difference between carbapenems and beta-lactams monotherapy or in combination. Conclusion: Meropenem and imipenem/cilastatin monotherapy appears to be available treatment for FN compared with beta-lactams. Imipenem/cilastatin was related to higher risk of AEs. Balancing the evidence for drug efficacy and side effects, meropenem monotherapy appears to be available treatment for FN. Individual centers should select the best matching therapy regimens according to local epidemiology and susceptibility patterns.