Defining the potency of amikacin against Escherichia coli, Klebsiella pneumoniae, Pseudomonas aeruginosa, and Acinetobacter baumannii derived from Chinese hospitals using CLSI and inhalation-based breakpoints

Abstract

Objectives: We report the in vitro activity of amikacin and comparators against Gram-negative bacteria collected from blood and respiratory specimens in China during a 1-year period between December 2015 and December 2016. Materials and methods: Minimum inhibitory concentrations (MICs) were determined by agar dilution methods using Clinical and Laboratory Standards Institute (CLSI) guidelines, and susceptibility was assessed using CLSI breakpoints, except for tigecycline against Enterobacteriaceae. A pharmacodynamic threshold MIC ≤ 256 mg/L was also applied for amikacin since its inhalation formulation has demonstrated activity up to these MICs. Results: For Escherichia coli, including extended-spectrum beta-lactamase (ESBL)-producing isolates (45.7% of population), amikacin demonstrated excellent activity (93.0%-94.7% susceptible) similar to tigecycline, piperacillin/tazobactam, and the carbapenems. Against Klebsiella pneumoniae, only tigecycline retained susceptibility >90%; amikacin inhibited 83.7% and 71.1% of the total and ESBL-producing (24.2%) populations at its breakpoint, respectively. Amikacin susceptibility against Pseudomonas aeruginosa was 91.1%, and only polymyxin B (100%) achieved higher susceptibility rates. Susceptibility declined to 80.9% and 54.5% against carbapenem- and multidrug-resistant (MDR) isolates, respectively. Finally, MDR was very common (84.0%) among Acinetobacter baumannii, with amikacin susceptibility at 30.5% for all isolates and 17.3% for MDR isolates. Since the majority of the amikacin-resistant isolates had amikacin MICs > 256 mg/L, the use of the inhalation pharmacodynamic threshold did not substantially improve the CLSI susceptible value. Conclusion: Amikacin portrayed comparable or better susceptibility rates to most of the tested antibiotics against E. coli, K. pneumoniae, P. aeruginosa, and A. baumannii in China. As few isolates had MICs of 32-256 mg/L, use of the CLSI breakpoint and inhalation pharmacodynamic threshold yielded similar overall susceptibilities.