Affiliation:
1. Laboratoire de Recherche Moléculaire sur les Antibiotiques, Université Paris VI, Faculté de Médecine Pitié-Salpêtrière, Paris, France.
Abstract
In Pseudomonas aeruginosa, resistance to imipenem is mainly related to a lack of protein OprD and resistance to fluoroquinolones is mainly related to alterations in DNA gyrase. However, strains cross resistant to fluoroquinolones and imipenem have been selected in vitro and in vivo with fluoroquinolones. We investigated the mechanisms of resistance to fluoroquinolones in 30 clinical strains of P. aeruginosa resistant to ciprofloxacin (mean MIC, >8 micrograms/ml), 20 of which were also resistant to imipenem (mean MIC, >16 micrograms/ml). By immunoblotting, OprD levels were markedly decreased in all of the imipenem-resistant strains. Plasmids carrying the wild-type gyrA gene (pPAW207) or gyrB gene (pPBW801) of Escherichia coli were introduced into each strain by transformation. MICs of imipenem did not change after transformation, whereas those of ciprofloxacin and sparfloxacin dramatically decreased (25- to 70-fold) for all of the strains. For 28 of them (8 susceptible and 20 resistant to imipenem), complementation was obtained with pPAW207 but not with pPBW801. After complementation, the geometric mean MICs of ciprofloxacin and sparfloxacin (MICs of 0.3 microgram/ml and 0.5 microgram/ml, respectively) were as low as those for wild-type strains. Complementation was obtained only with pPBW801 for one strain and with pPAW207 and pPBW801 for one strain highly resistant to fluoroquinolones. These results demonstrate that in clinical practice, gyrA mutations are the major mechanism of resistance to fluoroquinolones even in the strains of P. aeruginosa resistant to imipenem and lacking OprD, concomitant resistance to these drugs being the result of the addition of at least two independent mechanisms.
Publisher
American Society for Microbiology
Subject
Infectious Diseases,Pharmacology (medical),Pharmacology
Reference42 articles.
1. Emergence of quinoloneimipenem cross resistance in Pseudomonas aeruginosa after fluoroquinolone therapy;Aubert G.;J. Antimicrob. Chemother.,1992
2. Imipenem resistance in Pseudomonas aeruginosa resulting from diminished expression of an outer membrane protein;Büscher K. H.;Antimicrob. Agents Chemother.,1987
3. Mechanisms of resistance to quinolones;Cambau E.;Drugs,1993
4. Cambau E. E. Perani C. Dib C. Petinon and V. Jarlier. 1993. Role of modification of DNA gyrase in the resistance to ciprofloxacin of Pseudomonas aeruginosa sensitive or resistant to imipenem abstr. 1100 p. 320. In Program and abstracts of the 33rd Interscience Conference on Antimicrobial Agents and Chemotherapy. American Society for Microbiology Washington D.C.
5. Factors influencing the accumulation of ciprofloxacin in Pseudomonas aeruginosa;Celesk R. A.;Antimicrob. Agents Chemother.,1989
Cited by
31 articles.
订阅此论文施引文献
订阅此论文施引文献,注册后可以免费订阅5篇论文的施引文献,订阅后可以查看论文全部施引文献