Journal Article

Preservation of topoisomerase genetic sequences during <i>in vivo</i> and <i>in vitro</i> development of high-level resistance to ciprofloxacin in isogenic <i>Stenotrophomonas maltophilia</i> strains

Sylvia Valdezate, Ana Vindel, Juan Antonio Saéz-Nieto, Fernando Baquero and Rafael Cantón

in Journal of Antimicrobial Chemotherapy

Published on behalf of British Society for Antimicrobial Chemotherapy

Volume 56, issue 1, pages 220-223
Published in print July 2005 | ISSN: 0305-7453
Published online May 2005 | e-ISSN: 1460-2091 | DOI: http://dx.doi.org/10.1093/jac/dki182
Preservation of topoisomerase genetic sequences during in vivo and in vitro development of high-level resistance to ciprofloxacin in isogenic Stenotrophomonas maltophilia strains

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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.

Keywords: QRDR; fluoroquinolone resistance; efflux pump inhibitors

Journal Article.  2317 words. 

Subjects: Medical Oncology ; Critical Care

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