Performance of polymyxin B Etest in a setting of high prevalence of KPC-producing Klebsiella pneumoniae

Abstract

Objectives: Polymyxin resistance has been increasing in many regions, and appropriate determination of polymyxin susceptibility is now a major challenge worldwide. Many clinical laboratories rely on gradient diffusion methods to assess polymyxin susceptibility, although broth microdilution (BMD) is the only method currently recommended by the CLSI and EUCAST. The aim of this study was to assess the performance of the polymyxin B (PMB) Etest in a setting with a high prevalence of KPC-producing Klebsiella pneumoniae (KPC-KP). Methods: A commercial Etest susceptibility testing method was evaluated and compared with the reference BMD method, considering isolates with a minimum inhibitory concentration (MIC) ≤2 mg/L for PMB as susceptible to this drug. A total of 310 clinical KPC-KP isolates were evaluated. Results: Susceptibility was significantly higher by Etest compared with BMD (82.6% vs. 75.8%). The MIC50, MIC90 and modal MICs for PMB were 0.25, 32 and 0.25 mg/L (27.1%) by BMD and 0.5, 16 and 0.5 mg/L (49.7%) by Etest, respectively. Although categorical agreement was 90.0%, there was poor essential agreement (50.6%). A high rate (34.7%) of very major errors (VMEs) and a relatively low rate (2.1%) of major errors were found. Conclusion: The considerable number of resistant isolates in this study allowed an accurate estimation of VME rates and, consequently, a more comprehensive assessment of susceptibility testing for polymyxins. Etest did not meet fully the acceptance criteria for US FDA requirements. These data do not support the use of this commercial method for determining PMB MICs in carbapenem-resistant Enterobacterales populations.

Keywords

• Broth microdilution
• Carbapenem resistance
• Colistin
• Gradient test
• Klebsiella pneumoniae
• Polymyxin B