In vitro activities of imipenem, vancomycin, and rifampicin against clinical Elizabethkingia species producing BlaB and GOB metallo-beta-lactamases

Abstract

Elizabethkingia genus is emerging in hospitals and resistant to multiple antibiotics. The intrinsic imipenem resistance of Elizabethkingia genus is related to two chromosome-encoded metallo-beta-lactamases (MBLs), BlaB and GOB. This study was aimed to investigate the in vitro activity of imipenem, vancomycin, and rifampicin in clinical Elizabethkingia species. The distribution and heterogeneity of MBLs responsible for imipenem resistance were also evaluated. A total of 167 Elizabethkingia isolates from different patients were collected, including E. anophelis (142), E. meningoseptica (11), and E. miricola (14). All isolates were evaluated by the broth microdilution assay, ethylenediaminetetraacetic acid (EDTA) combination disk test, and EDTA-based microdilution test. The characteristics of BlaB and GOB were evaluated in phylogenetic analysis and heterologous expression experiments. Most of the isolates were susceptible to rifampin (94%), whereas none of the isolates were susceptible to imipenem. Vancomycin showed intermediate effectiveness. EDTA could reduce 4 folds or more minimum inhibitory concentrations (MICs) of imipenem in 105 isolates (62.9%). Of the isolates, the amino acid sequences of BlaB and GOB were divided into 22 and 25 different types, respectively. Phylogenetic analysis showed BlaB and GOB are species-specific proteins. Furthermore, GOB and BlaB from E. anophelis showed higher imipenem hydrolysis efficiency than those from the other two species. Rifampicin remained the most active agent in the current study. The mechanism of Elizabethkingia resistance to imipenem primarily stemmed from MBLs but other mechanisms could also exist, which requires further investigation.