Is ceftazidime/avibactam an option for serious infections due to ESBL and AmpC producing Enterobacterales?: a systematic review and meta-analysis.

Carbapenem sparing regimens are needed for the treatment of ESBL/AmpC producing Enterobacterales infections. We sought to compare the clinical efficacy of ceftazidime/avibactam and carbapenems against ESBL/AmpC producing Enterobacterales spp. A systematic review and meta-analysis of randomized controlled trials comparing ceftazidime/avibactam with carbapenems for the treatment of ESBL/AmpC producing Enterobacterales was conducted. Five RCTs with ESBLs/AmpC specific outcome data were compiled. Of the 246 patients infected with an ESBL producing microorganism in the ceftazidime/avibactam arm, 224 (91%) had a clinical response at TOC versus 240 of 271 (89%) patients in the carbapenem arm (RR 1.02, 95% CI 0.97-1.08, P=0.45, I 2=0%). Clinical response for AmpC producers in the ceftazidime/avibactam and carbapenem arms were 32/40 (80%) and 37/42 (88%), respectively (RR 0.91, 95% CI 0.76-1.10, P=0.35, I 2=0%). Microbiological response and mortality rates were not reported specifically for ESBL/AmpC producers. Ceftazidime/avibactam may be a carbapenem-sparing option for the treatment of mild to moderate complicated urinary tract and intraabdominal infections caused by ESBL producing Enterobacterales spp. and the data are limited to provide any conclusive recommendations for the AmpC producers. Care should be taken before extrapolating this to severe infections, given that the representation of this population in the reviewed studies was negligible. Ceftazidime/avibactam is a costly drug active against carbapenem resistant microorganisms, and should be used judiciously to preserve its activity against these.