Mutations in gyrA and parC associated with resistance to fluoroquinolones in epidemiologically defined clinical strains of Acinetobacter baumannii.

Abstract

mutations. Mutations in the gyrA gene were present in 49 of 147 strains (33%); double mutations in both gyrA and parC genes were detected in 25 strains (17%). The spectrum of mutations and the corresponding MIC distributions of the various compounds are shown in Table 1. Mutations were significantly more frequent in outbreak-related strains compared with sporadic strains (62% versus 23%; P = 0.005; OR 2.6; 95% CI 1.3–5.5). Double mutations leading to high-level ciprofloxacin resistance (MICs ≥ 32 mg/L) and decreased susceptibility to newer quinolones were found in 26% of outbreak-related strains and 14% of sporadic strains. This is consistent with the suggestion that resistance to fluoroquinolones could be a risk factor for epidemic behaviour in A. baumannii. 1 There were no significant differences in the activity of ciprofloxacin and the various newer quinolones against strains without mutations in gyrA or parC. Against strains with mutations, there was a correlation between the substituting amino acid and the resulting median MIC of the quinolone compounds (Table 1). The newer quinolones were up to three times more active than ciprofloxacin against A. baumannii strains with a single mutation, and up to five times against strains with a double mutation. Vila et al. 2,3 described mutations in gyrA and parC of 15 A. baumannii strains that correlated with resistance to ciprofloxacin. Among 25 Acinetobacter isolates obtained from various locations worldwide, Seward & Towner 7 confirmed mutations in gyrA and parC of 11 ciprofloxacin-resistant isolates and showed that 10 of these isolates were epidemiologically unrelated, as determined by randomly amplified polymorphic DNA analysis. Our findings confirmed that substitution of Ser-83 in GyrA is sufficient to confer ciprofloxacin MICs of ≥4 mg/L. In agreement with other stud