PREVALENCE OF A PUTATIVE EFFLUX MECHANISM AMONG FLUOROQUINOLONE-RESISTANT CLINICAL ISOLATES OF STREPTOCOCCUS-PNEUMONIAE

Twenty-three norfloxacin-selected first-step mutants of Streptococcus pneumoniae showed low-level fluoroquinolone resistance. Their suscepti bility to norfloxacin in the presence or absence of reserpine and know n efflux pump substrates was determined by an agar dilution method. Fi ve mutants showed four- to eightfold increases in their susceptibility to norfloxacin in the presence of reserpine and four- to eightfold de creases in their susceptibility to acriflavine and ethidium bromide, T his phenotype is suggestive of an efflux mechanism of resistance. A re presentative of these mutants, 1N27, accumulated significantly less et hidium bromide than the parent strain; reserpine abolished these diffe rences. No changes in the quinolone resistance determining regions of parC, parE, gyrA, or gyrB were found in this mutant. By our validated agar dilution method, the efflux phenotype was sought in clinical isol ates of S, pneumoniae, Of 1,037 clinical isolates examined from the Un ited Kingdom, 273 showed reduced susceptibility to norfloxacin or cipr ofloxacin. Of these, 45.4% showed the efflux phenotype, Our findings s uggest that an efflux mechanism may be a frequent cause of clinically significant fluoroquinolone resistance in pneumococci.