Reduced Ceftazidime-Avibactam Susceptibility in KPC-Producing Klebsiella pneumoniae From Patients Without Ceftazidime-Avibactam Use History – A Multicenter Study in China

Abstract

KPC-producing Klebsiella pneumoniae (KPC-KP) is the most widely spread carbapenem-resistant Enterobacteriaceae (CRE) in China. Avibactam is a novel non-β-lactam β-lactamase inhibitor which is highly active against KPC. Recently, ceftazidime-avibactam (CAZ-AVI) was approved for clinical treatment in China. Here we conducted a retrospective study to examine the antimicrobial susceptibility of CAZ-AVI prior to its usage in China, and evaluated the potential to develop resistance in KPC-KP. CAZ-AVI MICs were tested in 347 KPC-KP isolates collected from patients with no prior treatment with this combination from six medical centers in China. Almost all isolates (n = 346; 99.7%) were CAZ-AVI-susceptible, with only 12 (3.5%) which showed reduced susceptibility (MIC ≥ 4/4 μg/ml) or resistance. The 12 isolates belong to ST11 and half of them carry virulence genes. In comparison to susceptible isolates, these isolates demonstrated higher blaKPC–2 copy numbers and expressions, and demonstrated higher frequency of developing CAZ-AVI resistance.