Serum bactericidal activity of gemifloxacin versus clarithromycin against Streptococcus pneumoniae with different susceptibility to quinolones.
The objective of this study was to determine serum bactericidal titers (SBT, the highest dilution of serum showing no growth) and the serum bactericidal activity (SBA, i.e. duration of SBT greater than 1:2) as well as the serum bactericidal rate of gemifloxacin and clarithromycin after single doses in healthy male volunteers against Streptococcus pneumoniae. Strains tested had various degrees of susceptibility to penicillin as well as different susceptibility to quinolones due to a different QRDR mutation pattern (parC, gyrA). Serum samples from volunteers (n = 12) who had received a single oral dose of either 320 mg gemifloxacin or 500 mg clarithromycin in an open-label crossover study were obtained over a 24-hour period. SBA was determined, using the microdilution method. SBA of wildtype strains for gemifloxacin ranged from 8.9 to 15.4 h (mean 12.6 h). For gemifloxacin, 2 strains with solitary gyrA mutation had an SBA from 4.5 to 4.7 h (median 4.5 h). One of the 2 strains with a single QRDR mutation in parC displayed an SBA of 4.5 h, comparable to the gyrA mutation strains, whereas the second strain had a nearly twice as long SBA of 8.9 h. Two strains with two mutations (parC and gyrA) did not display any SBA. For clarithromycin, the duration of SBA ranged from 11.3 to 15.5 h (mean 13.6 h) for 6 of the 12 strains with an MIC < or = 0.06 mg/L (no SBA was found for the remaining strains, with an MIC of 0.25 mg/L or higher). In conclusion, a correlation between individual serum concentrations and SBA was found for both antibiotics.
Malerczyk
C
C
Institut für Pharmakologie, Philipps Universität, D-35033 Marburg, Germany.
Kolbert
M
M
Kinzig-Schippers
M
M
Sörgel
F
F
Machka
K
K
Shah
P M
PM
D000284:Administration, Oral; D000293:Adolescent; D000328:Adult; D000900:Anti-Bacterial Agents / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D017291:Clarithromycin / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004252:DNA Mutational Analysis; D004269:DNA, Bacterial; D024881:Drug Resistance, Bacterial; D004359:Drug Therapy, Combination; D024841:Fluoroquinolones / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D000077735:Gemifloxacin; D006801:Humans; D008297:Male; D008875:Middle Aged; D009287:Naphthyridines / Q000008:administration & dosage / Q000493:pharmacokinetics / Q000494:pharmacology*; D011008:Pneumococcal Infections / Q000188:drug therapy*; D015363:Quinolones / Q000494:pharmacology*; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000472:pathogenicity*
D000900:Anti-Bacterial Agents; D004269:DNA, Bacterial; D024841:Fluoroquinolones; D009287:Naphthyridines; D015363:Quinolones; D017291:Clarithromycin; D000077735:Gemifloxacin