Comparative efficacy and safety of β-lactam/β-lactamase inhibitors versus cabapenems for febrile neutropenia empiric therapy: A systematic review and meta analysis

Background: The efficacy and safety of β-lactam/β-lactamase inhibitors (BL/BLIs) versus carbapenems for febrile neutropenia empiric therapy are controversial. Methods PubMed, Embase, Cochrane library databases, Web of Science and Google scholar were searched up to 1 April 2020. Studies were included if they compared BL/BLIs versus carbapenem for febrile neutropenia patients undergoing chemotherapy for either solid tumours or haematological malignancies among adults and children. We pooled the treatment success rate, mortality and adverse events. Results Nine RCTs were included. There was no differences between carbapenems and BL/BLIs were observed in terms of treatment success without modification (RR 1.04, 95% CI 0.93–1.15), no differences were observed in the subgroups of BL/BLIs, adults and children. No significant differences were found in all-cause mortality (RR 1.15, 95% CI 0.64–2.06). Our study shows that gastrointestinal events are the most common adverse effects, nausea/vomiting were significantly more common with carbapenems (RR 2.83, 95% CI 1.35–5.92, P  = 0.006), however, diarrhea were more common with BL/BLIs (RR 0.47, 95% CI 0.27–0.80, P  = 0.006). Conclusions The efficacy and safety of BL/BLIs with carbapenems were comparable in empiric treatment of febrile neutropenia.