NON-GYRA-MEDIATED CIPROFLOXACIN RESISTANCE IN LABORATORY MUTANTS OF STREPTOCOCCUS-PNEUMONIAE

Two strains of Streptococcus pneumoniae, M4 (NCTC 7465, type strain) a nd M5 (clinical isolate), and their respective ciprofloxacin-resistant mutants, M4/C1, M5/C1 and M5/C3, were evaluated. All mutants were sta ble after one year's storage and all grew more slowly in Brain Heart I nfusion broth than the parent. The MICs of ciprofloxacin, sparfloxacin and tosufloxacin were increased for the mutants of M4, whereas the mu tants of M5 were less susceptible to ciprofloxacin only. The optimal b actericidal concentration (OBC) of each quinolone for all the strains was approximately ten-fold greater than the MIG. The OBCs for the muta nts were increased for ciprofloxacin, but not for the other two quinol ones. The DNA synthesis IC50 values of all quinolones correlated well with the MIC of each drug. AII quinolones accumulated rapidly within a il five strains; 10 mM magnesium chloride decreased the concentration of quinolone accumulated, but carbonyl cyanide m-chlorophenyl hydrazon e had no effect. Mutant strains M4/C1, M5/C1 and M5/C3 accumulated les s quinolone than their respective parent strains. DNA sequencing of th ose regions of gyrA and gyrB corresponding to the quinolone resistance -determining region in other bacteria did not reveal any differences b etween the parent and mutant strains.