Resistance to ceftazidime/avibactam in infections and colonisations by KPC-producing Enterobacterales: a systematic review of observational clinical studies

Ceftazidime/avibactam (CAZ-AVI), approved in 2015, is an important first-line option for Klebsiella pneumoniae carbapenemase-producing Enterobacterales (KPC-E). Although still uncommon, resistance to CAZ-AVI has emerged and may represent a serious cause of concern. We performed systematic literature review clinical microbiological features infections colonisations by CAZ-AVI-resistant KPC-E, focused on the vivo emergence different scenarios. Twenty-three papers were retrieved accounting 42 patients 57 isolates, mostly belonging K. ST258 harbouring D179Y substitution KPC enzyme. The USA, Greece Italy accounted 80% cases. In one-third isolates was not associated with previous exposure. Moreover, 20% strains colistin-resistant extended-spectrum β-lactamase (ESBL)-producers. majority infected had severe underlying diseases (39% cancer, 22% solid-organ transplantation) 37% died. abdomen, lung blood most involved infection sites. Infections mainly treated combination therapy (85% cases), meropenem being common (65%) followed tigecycline (30%), gentamicin (25%), colistin (25%) fosfomycin (10%). Despite resistance, 35% received CAZ-AVI. Taken together, these data highlight need prompt susceptibility testing including Enterobacterales, at least critical areas. Resistance urgent issue monitor order improve both empirical targeted use as well management caused strains.