Generating Genotype-Specific Aminoglycoside Combinations with Ceftazidime/Avibactam for KPC-Producing <i>Klebsiella pneumoniae</i>
Yanqin Huang, Karol Sokolowski, Amisha P. Rana, Nidhi Singh, Jiping Wang, Ke Chen, Yinzhi Lang, Jieqiang Zhou, Neera Kadiyala, Fiorella Krapp, Egon A. Ozer, Alan R. Hauser, Jian Li, Jürgen B. Bulitta, Zackery P. Bulman
Abstract
Antibiotic combinations, including ceftazidime/avibactam (CAZ/AVI), are frequently employed to combat KPC-producing Klebsiella pneumoniae (KPC-Kp), though such combinations have not been rationally optimized. Clinical KPC-Kp isolates with common genes encoding aminoglycoside-modifying enzymes (AMEs), aac(6′)-Ib′ or aac(6′)-Ib , were used in static time-kill assays ( n = 4 isolates) and the hollow-fiber infection model (HFIM; n = 2 isolates) to evaluate the activity of gentamicin, amikacin, and CAZ/AVI alone and in combinations.