J Glob Antimicrob Resist. 2021 Apr 22:S2213-7165(21)00091-6. doi: 10.1016/j.jgar.2021.04.001. Online ahead of print.
Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for KPC-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represents a serious cause of concern. We performed a systematic literature review of clinical and microbiological features of infections and colonizations from CAZ-AVI-resistant KPC-E, focused on the in vivo emergence of CAZ-AVI resistance in different clinical scenarios. Twenty-three papers were retrieved accounting for 42 patients and 57 isolates, mostly belonging to K. pneumoniae ST258 harboring D179Y substitution in KPC enzyme. United States, Greece and Italy accounted for 80% of cases. In one third of the isolates resistance was not associated with previous CAZ-AVI exposure. Twenty percent of the strains were colistin-resistant and 80% were extended spectrum beta-lactamases (ESBL) producers. The majority of infected patients had severe underlying diseases (39% had cancer and 22% were solid organ transplant recipients) and 37% died. Abdomen, lung and blood were the most involved infection sites. Infections from CAZ-AVI-resistant strains were mainly treated with combination therapy (85% of cases), with meropenem as the commonest antibiotic (65%) followed by tigecycline (30%), gentamicin (25%), colistin (25%) and fosfomycin (10%). Despite the emergence of resistance, 35% of patients received CAZ-AVI. Taken together these data highlight the need for a prompt susceptibility testing including CAZ-AVI for Enterobacterales, at least in critical areas. Resistance to CAZ-AVI is an urgent issue to monitor in order to improve both empirical and targeted CAZ-AVI use, as well as the management of patients with infections caused by CAZ-AVI-resistant strains.