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.
Highlights
With the widely use of carbapenem antibiotics, carbapenem-resistant Enterobacteriaceae (CRE) have been increasingly detected worldwide
In this collection 347 (56.3%) K. pneumoniae contained blaKPC, without coexistence of metalloβ-lactamases genes, the majority of which were from Kunming (119, 34.3%) followed by Chengdu (97, 28.0%), Guangzhou (49, 14.1%), Beijing (34, 9.8%), Suzhou (25, 7.2%), and Yinchuan (23, 6.6%) (Table 1)
Minimal inhibitory concentrations of CAZ-AVI inhibiting KPCKP ranged from ≤0.125/4 to 16/4 μg/ml, with only one strain which was resistant (16/4 μg/ml) according to the CLSI breakpoint (Clinical and Laboratory Standards Institute, 2018)
Summary
With the widely use of carbapenem antibiotics, carbapenem-resistant Enterobacteriaceae (CRE) have been increasingly detected worldwide. The production of carbapenemases is the leading cause of carbapenem resistance in CRE. Klebsiella pneumoniae carbapenemase (KPC) is currently the most widely spread carbapenemase in the world, including China (Nordmann and Poirel, 2014), Reduced CAZ-AVI Susceptibility in KPC-KP while K. pneumoniae is the main clinical species producing KPC (Zhang et al, 2017). KPC-type β-lactamases could hydrolyze carbapenems and almost all β-lactam antibiotics, and traditional β-lactamase inhibitors have limited effects on KPC (PappWallace et al, 2010). Isolates producing KPC are commonly resistant to many other clinical agents (Pollett et al, 2014) due to the co-expression of several resistant determinants. Novel treatments for infections caused by KPC-producing K. pneumoniae (KPC-KP) are in urgent need
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