Fluoroquinolone resistance in carbapenem-resistant Elizabethkingia anophelis: phenotypic and genotypic characteristics of clinical isolates with topoisomerase mutations and comparative genomic analysis.

Abstract

MDR Elizabethkingia anophelis strains are implicated in an increasing number of healthcare-associated infections worldwide, including a recent cluster of E. anophelis infections in the Midwestern USA associated with significant morbidity and mortality. However, there is minimal information on the antimicrobial susceptibilities of E. anophelis strains or their antimicrobial resistance to carbapenems and fluoroquinolones. Our aim was to examine the susceptibilities and genetic profiles of clinical isolates of E. anophelis from our hospital, characterize their carbapenemase genes and production of MBLs, and determine the mechanism of fluoroquinolone resistance. A total of 115 non-duplicated isolates of E. anophelis were examined. MICs of antimicrobial agents were determined using the Sensititre 96-well broth microdilution panel method. QRDR mutations and MBL genes were identified using PCR. MBL production was screened for using a combined disc test. All E. anophelis isolates harboured the blaGOB and blaB genes with resistance to carbapenems. Antibiotic susceptibility testing indicated different resistance patterns to ciprofloxacin and levofloxacin in most isolates. Sequencing analysis confirmed that a concurrent GyrA amino acid substitution (Ser83Ile or Ser83Arg) in the hotspots of respective QRDRs was primarily responsible for high-level ciprofloxacin/levofloxacin resistance. Only one isolate had no mutation but a high fluoroquinolone MIC. Our study identified a strong correlation between antibiotic susceptibility profiles and mechanisms of fluoroquinolone resistance among carbapenem-resistant E. anophelis isolates, providing an important foundation for continued surveillance and epidemiological analyses of emerging E. anophelis opportunistic infections. Minocycline or ciprofloxacin has the potential for treatment of severe E. anophelis infections.