Defining the potency of amikacin against <em>Escherichia coli</em>, <em>Klebsiella pneumoniae</em>, <em>Pseudomonas aeruginosa</em>, and <em>Acinetobacter baumannii</em> 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. Keywords: Gram-negative, resistance, minimum inhibitory concentration, aminoglycoside