Ertapenem non-susceptibility and independent predictors of the carbapenemase production among the Enterobacteriaceae isolates causing intra-abdominal infections in the Asia-Pacific region: results from the Study for Monitoring Antimicrobial Resistance Trends (SMART)

Shio-Shin Jean,1,2 Wen-Sen Lee,3,4 Po-Ren Hsueh5,6 on behalf of the SMART Asia-Pacific Group 1Department of Emergency, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 2Department of Emergency Medicine, Department of Emergency and Critical Care Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 3Division of Infectious Diseases, Department of Internal Medicine, Wan Fang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan; 5Departments of Laboratory Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan; 6Department of Internal Medicine, National Taiwan University Hospital, National Taiwan University College of Medicine, Taipei, Taiwan Objectives: This study investigated the prevalence rates of carbapenemase positivity, antibiotic susceptibility, and independent predictors of carbapenemase producers among the Enterobacteriaceae isolates recovered from patients with intra-abdominal infections (IAI) in the Asia-Pacific region between 2008 and 2014.Materials and methods: Multiplex PCR was used for the detection of specific β-lactamases, while the broth microdilution method was used to determine the minimum inhibitory concentrations (MICs) of antibiotics among the IAI-related Enterobacteriaceae isolates. We studied the abovementioned parameters in 484 ertapenem-non-susceptible (Erta-NS) isolates and explored the independent predictors of carbapenemase-producing Enterobacteriaceae (CPE) isolates.Results: Eighty (16.5%) Erta-NS-IAI Enterobacteriaceae isolates were found to be CPE. Vietnam and the Philippines had the highest CPE prevalence rates. The IAI isolates of Enterobacter species and Klebsiella pneumoniae followed by Escherichia coli were the three major pathogens with 77.4%, 40.9%, and 11.7% Erta-NS prevalence rates, respectively. Furthermore, the highest CPE prevalence (35%) was noted among the Erta-NS-K. pneumoniae isolates. The CPE isolates harboring the blaNDM, blaKPC, or blaOXA-48-like alleles had higher imipenem MIC levels than those harboring the blaIMP alleles. Using multivariate logistic regression analysis, we concluded that Erta-NS-IAI isolates with an imipenem non-susceptible phenotype (OR, 56.4), with cefepime MIC >8 µg/mL (OR, 4.4), cultured from the peritoneal space samples (tissue or abscess; OR, 3.3), and harboring the extended-spectrum β-lactamase encoding allele (OR, 11.5) are independent predictors of CPE.Conclusion: Imipenem non-susceptibility, cefepime MIC >8 μg/mL, and the peritoneal space as a culture site are independent clinical predictors of CPE among the Erta-NS-IAI Enterobacteriaceae isolates in the Asia-Pacific region. Keywords: intra-abdominal infection, antimicrobial susceptibility, ertapenem-non-susceptible, carbapenemase-producing Enterobacteriacea