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 cro ssover fashion. The 4-fold increase in ciprofloxacin MIC from the susceptib le 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 hi gher MIC (0.25 vs 0.06 mg.l), a 4-fold lower C-max/MIC (8.6 vs 36), a 4-fol d lower AUC(0-24) (h)/MIC (85 vs 356) and a 11-fold lower AUBCs (2 vs 22) a gainst the resistant isolate compared with the susceptible one. Trovafloxac in serum bactericidal titres against the ciprofloxacin-resistant strain wer e measurable generally only at 1 h after dosing (median titre = 2). Gemiflo xacin showed similar ex vivo bactericidal activity against the ciprofloxaci n-resist ant strain to that of trovafloxacin against the ciprofloxacin-susc eptible strain. (C) 2001 Elsevier Science B.V. and International Society of Chemotherapy. All rights reserved.