Journal of Antimicrobial Chemotherapy (1999) 44, 743-748
© 1999 The British Society for Antimicrobial Chemotherapy
Analysis of the mechanisms of quinolone resistance in clinical isolates of Citrobacter freundii
Departament de Microbiologia, IDIBAPS, Hospital Clínic, Facultat de Medicina, Universitat de Barcelona, Villarroel 170, 08036-Barcelona, Spain
The presence of gyrA, gyrB and/or parC mutations, quinolone
uptake,
outer membrane protein profiles and epidemiological relationship were studied in 12 clinical
isolates of Citrobacter freundii. No alterations were observed in the gyrB gene
of any of the
strains, or gyrA or parC of the four quinolone-susceptible strains (nalidixic acid
MIC
of 24 mg/L, and a ciprofloxacin MIC of 0.0060.06 mg/L). The
quinolone-resistant
strains were classified into two groups: one group (group A) composed of strains resistant to
nalidixic
acid but not to ciprofloxacin and another (group B) including those resistant to both antibiotics
with a
mutation at codon 83 of the gyrA gene (Thr
Ile), but no alteration in either parC or gyrB genes. In group B, three of the four resistant isolates, with a nalidixic
acid MIC > 1024 mg/L and ciprofloxacin MIC of 832 mg/L, showed concomitant
mutations at codons 83
and 87 of the gyrA gene (Thr
Ile and Asp
Tyr, respectively) as well as a
single
mutation in codon 80 of the parC gene (Ser
Ile). The fourth isolate did not possess
the
mutation at codon 87 of gyrA. Two strains belong to the same clone and, although they
had
the same type of mutations in the gyrA and parC genes, showed different MICs
of
ciprofloxacin. This difference was related to an efflux pump mechanism. Mutations in the gyrA and parC genes play the main role in quinolone resistance development in Citrobacter
freundii, although other factors such as overexpression of efflux pumps can play a
complementary
role and thus modulate the final quinolone MIC.
* Corresponding author. Tel: +34-3-2275522; Fax: +34-3-2275454; E-mail: vila{at}medicina.ub.es
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