Molecular epidemiology of quinolone resistance and comparative in vitro activities of new quinolones against European Staphylococcus aureus isolates

New fluoroquinolones (FQ) may possibly be used as alternative therapeutic o ptions for Staphylococcus aureus infections. Our objectives were: (1) to de fine the in vitro activities of seven FQs in a collection of 434 methicilli n-susceptible and 457 methicillin-resistant S. aureus from 23 European univ ersity hospitals; (2) to characterise the prevalence of mutations in the gr lA and gyrA genes in all ciprofloxacin-resistant (n = 433) isolates of S. a ureus; (3) to determine the percentage of ciprofloxacin resistant S. aureus strains with measurable quinolone efflux. Methods: (1) The in vitro activi ties of different FQs were determined by microdilution tests. (2) PCR-ampli fied DNA was sequenced. (3) Ciprofloxacin minimum inhibitory concentrations (MIC) were determined in the presence and absence of reserpine, which inhi bits efflux pumps. Results: (1) Irrespective of the methicillin resistance of the isolates, sitafloxacin and clinafloxacin showed the best in vitro ac tivities. (2) All ciprofloxacin-resistant isolates exhibited GrlA alteratio ns, namely Ser-80 --> Phe or Tyr or Glu-84 --> Lys or Ala-116 --> Glu or Pr o or a combination of Ser-80 --> Phe and Glu-84 --> Val. These alterations in GrlA were combined with alterations in GyrA, namely Ser-84 --> Leu or Ly s or Glu-88 --> Lys or Val. (3) Reserpine reduced ciprofloxacin MIC values in ca. 30% of the clinical isolates tested. Conclusions: (1) This current E uropean overview of mutations involved in FQ resistance demonstrates that o nly a limited number of classical mutations in grlA and gyrA contributed to resistance in clinical isolates. (2) An efflux pump is involved in ca. 30% of ciprofloxacin-resistant S. aureus isolates. (3) Sitafloxacin and clinaf loxacin are two very promising new FQs with good anti-staphylococcal activi ty. New FQs, perhaps ill combination with efflux pump inhibitors, might pla y a role in the treatment of S. aureus infections. (C) 1999 Federation of E uropean Microbiological Societies. Published by Elsevier Science B.V. All r ights reserved.