Frequencies and mechanisms of resistance to moxifloxacin in nosocomial isolates of Acinetobacter baumannii.
OBJECTIVE
To compare the in vitro activity of moxifloxacin and ciprofloxacin against 226 nosocomial isolates of Acinetobacter baumannii from 44 hospitals in the UK.


METHODS
MICs of ciprofloxacin and moxifloxacin were determined by Etest. PCR analysis was used to detect chromosomal mutations in the gyrA and parC genes. Isolates resistant to ciprofloxacin and susceptible to moxifloxacin were examined for the ability to generate spontaneous moxifloxacin-resistant isolates.


RESULTS
Of 226 isolates, 49.1% were resistant to ciprofloxacin and 39.4% were moxifloxacin-resistant according to BSAC criteria. Approximately 20% of isolates resistant to ciprofloxacin remained susceptible to moxifloxacin. A GyrA mutation at Ser-83 was found in all ciprofloxacin-resistant isolates. Single mutations in both the gyrA and parC genes at codons Ser-83 and Ser-80, respectively, were found in ciprofloxacin- and moxifloxacin-resistant isolates. Isolates that were ciprofloxacin-resistant but moxifloxacin-susceptible generated spontaneous moxifloxacin-resistant mutants when grown on medium containing up to 8x their initial MIC. However, these mutants were not stable and none displayed high-level moxifloxacin resistance.


CONCLUSIONS
Moxifloxacin retained in vitro activity against some ciprofloxacin-resistant clinical A. baumannii isolates. Mutations in both gyrA and parC were necessary for resistance to moxifloxacin in most isolates of A. baumannii.
Spence
Richard P
RP
Molecular Diagnostics and Typing Unit, Department of Microbiology, University Hospital, Queens Medical Centre, Nottingham NG7 2UH, UK.
Towner
Kevin J
KJ
D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000382:microbiology; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000254:growth & development; D001372:Aza Compounds / Q000494:pharmacology / Q000627:therapeutic use*; D003428:Cross Infection / Q000188:drug therapy* / Q000382:microbiology; D004305:Dose-Response Relationship, Drug; D024881:Drug Resistance, Bacterial / Q000187:drug effects* / Q000502:physiology; D024841:Fluoroquinolones; D006801:Humans; D008826:Microbial Sensitivity Tests / Q000379:methods; D000077266:Moxifloxacin; D011804:Quinolines / Q000494:pharmacology / Q000627:therapeutic use*
D001372:Aza Compounds; D024841:Fluoroquinolones; D011804:Quinolines; D000077266:Moxifloxacin