Influence of diminished susceptibility of Streptococcus pneumoniae to ciprofloxacin on the serum bactericidal activity of gemifloxacin and trovafloxacin after a single dose in healthy volunteers.
The serum bactericidal activity against 2 Streptococcus pneumoniae strains (ciprofloxacin MIC 1 and 4 mg/l) was measured in 12 volunteers who received oral single doses of gemifloxacin 320 mg and trovafloxacin 200 mg in a crossover fashion. The 4-fold increase in ciprofloxacin MIC from the susceptible to the resistant strain resulted in a 2-fold increase in MIC (from 0.015 to 0.03 mg/l), a 2-fold decrease in C(max)/MIC (104 vs 52) and in AUC(0-24 h)/MIC (532 vs 266), but a 5.6-fold decrease in area under the bactericidal curve (AUBC: 168 vs 30) for gemifloxacin. Trovafloxacin showed a 4-fold higher MIC (0.25 vs 0.06 mg/l), a 4-fold lower C(max)/MIC (8.6 vs 36), a 4-fold lower AUC(0-24 h)/MIC (85 vs 356) and a 11-fold lower AUBCs (2 vs 22) against the resistant isolate compared with the susceptible one. Trovafloxacin serum bactericidal titres against the ciprofloxacin-resistant strain were measurable generally only at 1 h after dosing (median titre=2). Gemifloxacin showed similar ex vivo bactericidal activity against the ciprofloxacin-resistant strain to that of trovafloxacin against the ciprofloxacin-susceptible strain.
Prieto
J
J
Microbiology Department, School of Medicine, Universidad Complutense de Madrid, Avda. Complutense s/n, 28040 Madrid, Spain. jprieto@eucmax.sim.ucm.es
Aguilar
L
L
Fuentes
F
F
Giménez
M J
MJ
Alou
L
L
Dal-Ré
R
R
Sörgel
F
F
Frías
J
J
D000328:Adult; D000890:Anti-Infective Agents / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000494:pharmacology; D004305:Dose-Response Relationship, Drug; D004352:Drug Resistance, Microbial / Q000235:genetics; D024841:Fluoroquinolones; D000077735:Gemifloxacin; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000097:blood / Q000493:pharmacokinetics / Q000494:pharmacology*; D015610:Serum Bactericidal Test; D013296:Streptococcus pneumoniae / Q000187:drug effects* / Q000235:genetics
D000890:Anti-Infective Agents; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; C080163:trovafloxacin; D000077735:Gemifloxacin