OBJECTIVES: To ascertain the participation of topoisomerase mutations in the development of ciprofloxacin resistance in isogenic Stenotrophomonas maltophilia mutants. METHODS: gyrAB and parCE sequences in three paired in vivo isogenic ciprofloxacin-susceptible (MIC range 0.5-4 mg/L) and resistant (16-128 mg/L) S. maltophilia strains (PFGE-characterized) sequentially isolated from three patients, and their corresponding in vitro mutants (ciprofloxacin MIC range 2->128 mg/L), were studied. Efflux phenotype was also investigated. RESULTS: Despite different quinolone susceptibilities, each paired clinical strain displayed identical gyrAB and parCE sequences as well as their corresponding in vitro mutants. Up to 50% (18/36) of in vitro mutants displayed a positive efflux phenotype when nalidixic acid was combined with MC-207,110, while 6% (2/36) showed the phenotype when exposed to nalidixic acid and reserpine. Carbonyl cyanide m-chlorophenylhydrazone or arsenite failed to alter quinolone MICs. CONCLUSIONS: The increase of ciprofloxacin MICs in in vivo and in vitro isogenic S. maltophilia mutant strains was not related to quinolone resistance determining region mutations. Highly effective efflux mechanisms might preserve topoisomerase targets from a ciprofloxacin challenge in S. maltophilia.
OBJECTIVES: To ascertain the participation of topoisomerase mutations in the development of ciprofloxacin resistance in isogenic Stenotrophomonas maltophilia mutants. METHODS: gyrAB and parCE sequences in three paired in vivo isogenic ciprofloxacin-susceptible (MIC range 0.5-4 mg/L) and resistant (16-128 mg/L) S. maltophilia strains (PFGE-characterized) sequentially isolated from three patients, and their corresponding in vitro mutants (ciprofloxacin MIC range 2->128 mg/L), were studied. Efflux phenotype was also investigated. RESULTS: Despite different quinolone susceptibilities, each paired clinical strain displayed identical gyrAB and parCE sequences as well as their corresponding in vitro mutants. Up to 50% (18/36) of in vitro mutants displayed a positive efflux phenotype when nalidixic acid was combined with MC-207,110, while 6% (2/36) showed the phenotype when exposed to nalidixic acid and reserpine. Carbonyl cyanide m-chlorophenylhydrazone or arsenite failed to alter quinolone MICs. CONCLUSIONS: The increase of ciprofloxacin MICs in in vivo and in vitro isogenic S. maltophilia mutant strains was not related to quinolone resistance determining region mutations. Highly effective efflux mechanisms might preserve topoisomerase targets from a ciprofloxacin challenge in S. maltophilia.
Authors: Theodore R Pak; Deena R Altman; Oliver Attie; Robert Sebra; Camille L Hamula; Martha Lewis; Gintaras Deikus; Leah C Newman; Gang Fang; Jonathan Hand; Gopi Patel; Fran Wallach; Eric E Schadt; Shirish Huprikar; Harm van Bakel; Andrew Kasarskis; Ali Bashir Journal: Antimicrob Agents Chemother Date: 2015-08-31 Impact factor: 5.191
Authors: Mark A Toleman; Peter M Bennett; David M C Bennett; Ronald N Jones; Timothy R Walsh Journal: Emerg Infect Dis Date: 2007-04 Impact factor: 6.883