Mutant prevention concentrations of levofloxacin, pazufloxacin and ciprofloxacin for A. baumannii and mutations in gyrA and parC genes

J Antibiot (Tokyo). 2015 May;68(5):313-7. doi: 10.1038/ja.2014.150. Epub 2014 Nov 5.

Abstract

Fluoroquinolones are antimicrobial agents that are widely used clinically, but the increasing resistance of Acinetobacter baumannii (A. baumannii) to these agents is a matter of concern. We investigated mutant prevention concentrations (MPCs) of three fluoroquinolones, levofloxacin (LVX), pazufloxacin (PAZ) and ciprofloxacin (CIP). We analyzed an A. baumannii standard strain (ATCC19606) for mutation prevention indices (MPIs), MPCs and mutant selection windows as well as MICs of CIP, PAZ and LVX and compared the derived values with 34 A. baumannii strains collected in hospitals. In addition, A. baumannii standard strain (ATCC19606) fluoroquinolone-resistant mutants were investigated for gyrA and parC gene mutations. MPCs of CIP, prevention antibiotics concentration and LVX for A. baumannii ATCC19606 were 12.8, 5.6 and 2.8 μg ml(-1) and their MPIs were 16, 8 and 4, respectively. Clinically isolated A. baumannii strains had CIP, PAZ and LVX MPC value ranges of 1-8, 1-16 and 0.5-2 μg ml(-1) and their MPIs were 8, 8 and 4 μg ml(-1). Single gyrA mutations (Ser(83)-Leu(83)) occurred in 18 resistant strains (48.7%) and single parC mutations (Ala(79)-Asp(79) or (Ser(80)-Leu(80)) occurred in 8 resistant strains (21.6%), whereas gyrA and parC double mutations occurred in 2 (5.4%) of the resistant strains. MPC and MPI values of LVX were lower than that of CIP and PAZ. Single gyrA and parC mutations accounted for the majority of mutations (n=24), whereas double mutations occurred only in two strains.

MeSH terms

  • Acinetobacter baumannii / drug effects*
  • Acinetobacter baumannii / genetics
  • Anti-Bacterial Agents / pharmacology
  • Ciprofloxacin / pharmacology*
  • DNA Gyrase / genetics
  • DNA Gyrase / metabolism*
  • DNA Topoisomerase IV / genetics
  • DNA Topoisomerase IV / metabolism*
  • DNA, Bacterial / genetics
  • Fluoroquinolones / pharmacology*
  • Gene Expression Regulation, Bacterial / physiology
  • Levofloxacin / pharmacology*
  • Microbial Sensitivity Tests
  • Mutation
  • Oxazines / pharmacology*

Substances

  • Anti-Bacterial Agents
  • DNA, Bacterial
  • Fluoroquinolones
  • Oxazines
  • pazufloxacin
  • Ciprofloxacin
  • Levofloxacin
  • DNA Topoisomerase IV
  • DNA Gyrase