Twelve healthy volunteers participated in this randomized crossover study to compare the concentrations and recovery levels of
fleroxacin and
pefloxacin in urine and to assess their bactericidal activities against 12 strains of urinary pathogens with different susceptibilities over a wide range of MICs. The volunteers received a single oral dose of 400 mg of
fleroxacin or 800 mg of
pefloxacin. The mean cumulative renal excretion of unchanged
fleroxacin, N-demethyl-
fleroxacin, and N-
oxide-
fleroxacin accounted for 67, 7, and 6% of the total dose, respectively. The total urinary recovery of
pefloxacin and the active metabolite
norfloxacin was 34%. In the time-kill and the urinary bactericidal titer (UBT) studies, only the subjects' urine not supplemented with broth was used. With most tested organisms and both
quinolones it took more than 8 h to achieve a reduction in CFU of 99.9% (3 log units). Overall, there was a good correlation between UBTs and MICs for the strains. Against Escherichia coli ATCC 25922 the median UBTs were similar for both
antibiotics and at least 1:8 for 96 h; against the E. coli strain for which the MIC was 0.5 microgram/ml the UBT was at least 1:4 for 48 h. The UBTs of both drugs against Klebsiella pneumoniae were at least 1:16 for 72 h. The UBTs for Staphylococcus aureus (the MIC for which was 16 micrograms/ml) of both
antibiotics were low, and in some of the samples, no bactericidal titers were observed. UBTs for Proteus mirabilis of
pefloxacin are significantly higher than those of
fleroxacin. For Pseudomonas aeruginosa the median UBTs were present for the 24-to-48-h interval. The same is true for Enterococcus faecalis. Against Staphylococcus saprophyticus, UBTs were present for at least 48 h with both
quinolones. Overall, a single oral dose of 400 mg of
fleroxacin exhibits UBTs comparable to those of 800 mg of
pefloxacin. Therefore, it may be expected that half of the dose of
fleroxacin gives comparable results in the treatment of
urinary tract infections; this should be substantiated in comparative clinical trials.