title: In vivo selection of a target/efflux double mutant of Pseudomonas aeruginosa by ciprofloxacin therapy.
abstract: We report the emergence after 4 days of ciprofloxacin monotherapy of a double mutant of Pseudomonas aeruginosa overexpressing the multidrug efflux system MexAB-OprM and harbouring a mutation in the gyrB gene. Compared with its initial susceptible counterpart, this mutant exhibited a significant increase in resistance to most of the beta-lactam antibiotics tested (16 x MIC of ticarcillin) and to ciprofloxacin (128 x MIC). Combined ceftazidime and amikacin therapy finally eradicated the resistant isolate and cured the patient of his infection. This case illustrates how strains of P. aeruginosa may develop high levels of fluoroquinolone resistance by combining efflux mechanisms and target alterations.
authors.affiliation: Laboratoire de Microbiologie, Hôpital Robert Debré, 48 Boulevard Serurier, F-75395 Paris cedex 19, France.
authors.forename: I
authors.initials: I
authors.lastname: Le Thomas
authors.forename: G
authors.initials: G
authors.lastname: Couetdic
authors.forename: O
authors.initials: O
authors.lastname: Clermont
authors.forename: N
authors.initials: N
authors.lastname: Brahimi
authors.forename: P
authors.initials: P
authors.lastname: Plésiat
authors.forename: E
authors.initials: E
authors.lastname: Bingen
mesh_terms: D000293:Adolescent; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001425:Bacterial Outer Membrane Proteins / Q000378:metabolism; D002352:Carrier Proteins / Q000378:metabolism; D002939:Ciprofloxacin / Q000494:pharmacology* / Q000627:therapeutic use*; D027081:DNA Gyrase / Q000235:genetics; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics* / Q000502:physiology; D006801:Humans; D007769:Lactams / Q000494:pharmacology; D026901:Membrane Transport Proteins; D008826:Microbial Sensitivity Tests; D009154:Mutation; D016133:Polymerase Chain Reaction; D011552:Pseudomonas Infections / Q000188:drug therapy / Q000382:microbiology; D011550:Pseudomonas aeruginosa / Q000187:drug effects / Q000235:genetics / Q000378:metabolism; D019105:Random Amplified Polymorphic DNA Technique
chemical_list: D000890:Anti-Infective Agents; D001425:Bacterial Outer Membrane Proteins; D002352:Carrier Proteins; D007769:Lactams; D026901:Membrane Transport Proteins; C118598:MexA protein, Pseudomonas aeruginosa; C118597:MexB protein, Pseudomonas aeruginosa; C402263:OprM protein, Pseudomonas aeruginosa; D002939:Ciprofloxacin; D027081:DNA Gyrase