PHARMACOKINETIC AND PHARMACODYNAMIC ACTIVITIES OF CIPROFLOXACIN AGAINST STRAINS OF STREPTOCOCCUS-PNEUMONIAE, STAPHYLOCOCCUS-AUREUS, AND PSEUDOMONAS-AERUGINOSA FOR WHICH MICS ARE SIMILAR

The serum bactericidal activity of ciprofloxacin against strains of St reptococcus pneumoniae, Staphylococcus aureus, and Pseudomonas aerugin osa for which MICs are similar (0.4 mu g/ml) was assessed with serum u ltrafiltrates from five healthy volunteers receiving ciprofloxacin at 400 mg intravenously every 8 h. In addition, human serum was supplemen ted with ciprofloxacin to achieve a mean steady-state concentration (C -ss) that might be achieved in patients with renal failure, with total clearances of 3 to 4 liters/h (elimination rate constant, 0.08 h(-1)) . The area under the inhibitory titer curve from 0 to 24 h (AUIC(24)) and the area under the bactericidal titer curve from 0 to 24 h (AUBC(2 4)) were both measured and predicted as the area under the concentrati on-time curve from 0 to 24 h (AUC(24))/MIC and AUC(24)/MBC, respective ly. We previously demonstrated that a breakpoint AUC(24)/MIC of 125 fo r ciprofloxacin had a significantly higher probability of treatment su ccess than lower values, with 250 to 500 being optimal. Volunteer sera (mean C-ss, 1.55 to 2.48 mu g/ml) achieved AUC,MICs of 90 to 145. Sup plemented serum (mean C-ss, 6.00 to 7.42 mu g/ml) achieved AUC(24)/MIC s of 350 to 450. Correlation coefficients for measured and predicted v alues of AUC(24)/MIC and AUC(24)/MBC mere 0.826 and 0.941, respectivel y. The mean percent errors were not significantly different from zero for either AUIC(24) or AUBC(24) values (P > 0.1, P > 0.4). Time-kill c urve studies were performed with low (1.55 to 2.48 mu g/ml), intermedi ate (6.00 to 7.42 mu g/ml), and high (15 to 25 mu g/ml) concentrations of ciprofloxacin for the three organisms. At low concentrations (3 to 6 times the MIC) AUC(24)/MICs were < 125 for two of five volunteers a nd the killing rates were considerably more rapid for P. aeruginosa th an for S. pneumoniae or S. aureus. Intermediate concentrations (15 to 18 times the MIC) achieved optimal AUC(24)/MICs, and the killing rates were similar for the three organisms. A paradoxical decrease in the k illing rate was seen at high concentrations (35 to 60 times the MIC). At clinically achievable concentrations, ciprofloxacin killed P. aerug inosa more rapidly than it did either S. pneumoniae or S. aureus.