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FEMS Immunol Med Microbiol. 1999 Dec;26(3-4):281-7.

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

Author information

1
Institute for Medical Microbiology and Virology, Heinrich-Heine University Düsseldorf, Universitätsstrasse 1, Geb. 22.21, 40225, Düsseldorf, Germany. schmidtfj@uni-duesseldorf.de

Abstract

New fluoroquinolones (FQ) may possibly be used as alternative therapeutic options for Staphylococcus aureus infections. Our objectives were: (1) to define the in vitro activities of seven FQs in a collection of 434 methicillin-susceptible and 457 methicillin-resistant S. aureus from 23 European university hospitals; (2) to characterise the prevalence of mutations in the grlA and gyrA genes in all ciprofloxacin-resistant (n=433) isolates of S. aureus; (3) to determine the percentage of ciprofloxacin-resistant S. aureus strains with measurable quinolone efflux.

METHODS:

(1) The in vitro activities of different FQs were determined by microdilution tests. (2) PCR-amplified DNA was sequenced. (3) Ciprofloxacin minimum inhibitory concentrations (MIC) were determined in the presence and absence of reserpine, which inhibits efflux pumps.

RESULTS:

(1) Irrespective of the methicillin resistance of the isolates, sitafloxacin and clinafloxacin showed the best in vitro activities. (2) All ciprofloxacin-resistant isolates exhibited GrlA alterations, namely Ser-80-->Phe or Tyr or Glu-84-->Lys or Ala-116-->Glu or Pro 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 Lys or Glu-88-->Lys or Val. (3) Reserpine reduced ciprofloxacin MIC values in ca. 30% of the clinical isolates tested.

CONCLUSIONS:

(1) This current European overview of mutations involved in FQ resistance demonstrates that only 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 clinafloxacin are two very promising new FQs with good anti-staphylococcal activity. New FQs, perhaps in combination with efflux pump inhibitors, might play a role in the treatment of S. aureus infections.

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