A pharmacodynamic evaluation of ciprofloxacin and ofloxacin against two strains of Pseudomonas aeruginosa

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Abstract
The greater potency of ciprofloxacin in vitro to that of ofloxacin against Pseudomonas aeruginosa may be potentially offset by the more favorable pharmacokinetic profile of the latter drug. In order to test this hypothesis, we generated time concentration kill curves for P. aeruginosa ATCC 27853 and a clinical isolate P. aeruginosa PSA 9258 using an in-vitro model to simulate the pharmacokinetic characteristics found in vivo for ciprofloxacin at a peak concentration (CPmax) of 5 mg/L and an elimination T½ of 4.5 h, and ofloxacin at a CPmax of 5 mg/L and a T½ of both 4.5 h and 6 h, and at a CPmax of 8.0 mg/L and a T½ of 6 h. A 3 log10 kill (T3 kill) of P. aeruginosa ATCC 27853 was achieved in 0.15 h by ciprofioxacin and of P. aeruginosa PSA 9258 in 0.09 h. Ofloxacin at a CPmax of 8 mg/L and T½ of 6 h achieved a T3 kill of P. aeruginosa ATCC 27853 in 0.74 h and of P. aeruginosa NA 9258 in 0.16 h. The area under the kill curve (AUKC) was 1.10×104 1.96×103 mL-h/cfu for ciprofloxacin against P. aeruginosa ATCC 27853 and P. aeruginosa PSA 9258, respectively and that of ofloxacin at CPmax 8 mg/L and a T½ of 6 h was 9.78×104 and 2.20×104 mL-h/cfu respectively. Significant differences (P≥0.05) were evident between ciprofloxacin and all ofloxacin regimens against P. aeruginosa ATCC 27853 but not against P. aeruginosaPSA 9258. There was a poor correlation (r=0.22) between the AUKC and area under the time concentration curve (AUC) for P. aeruginosa ATCC 27853 but a strong correlation (r=0.96) between the AUKC and area under the inhibitory curve (AUIC). Similar results were obtained for P. aeruginosa PSA 9258 for which the correlation between AUKC and AUC was weak (r=0.10) whereas that between the AUKC and AUIC was strong (r=0.93). When the data for both P. aeruginosa were combined, a correlation coefficient of r=0.04 for AUC and r=0.80 for AUIC was found. These limited data suggest that fluoroquinolones can be compared using the AUIC for specific bacterial isolates. In addition, the larger AUC, higher CP, and longer T½ of ofloxacin in vivo did not fully compensate for the intrinsic differences in the antibiotic susceptibility against P. aeruginosa.

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