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

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 T1/2 of 4.5 h, and ofloxacin at a CPmax of 5 mg/L and a T1/2 of both 4.5 h and 6 h, and at a CPmax of 8.0 mg/L and a T1/2 of 6 h. A 3 log10 kill (T3 kill) of P. aeruginosa ATCC 27853 was achieved in 0.15 h by ciprofloxacin and of P. aeruginosa PSA 9258 in 0.09 h. Ofloxacin at a CPmax of 8 mg/L and T1/2 of 6 h achieved a T3 kill of P. aeruginosa ATCC 27853 in 0.74 h and of P. aeruginosa PSA 9258 in 0.16 h. The area under the kill curve (AUKC) was 1.10 x 10(4)and 1.96 x 10(3) 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 T1/2 of 6 h was 9.78 x 10(4)and 2.20 x 10(4) mL-h/cfu respectively. Significant differences (P > or = 0.05) were evident between ciprofloxacin and all ofloxacin regimens against P. aeruginosa ATCC 27853 but not against P. aeruginosa PSA 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 T1/2 of ofloxacin in vivo did not fully compensate for the intrinsic differences in the antibiotic susceptibility against P. aeruginosa.

Application of an In Vitro Infection Model and Simulation for Reevaluation of Fluoroquinolone Breakpoints for Salmonella enterica Serotype Typhi

“…Moreover, a number of clinical studies involving fluoroquinolones have demonstrated similar exposure-response relationships as those derived from animal and in vitro infection models, for both gram-positive and -negative organisms. Findings from in vitro and animals models are in agreement with clinical data, where fAUC 0-24 / MIC ratios of 125 are associated with optimal fluoroquinolone activity for gram-negative bacilli (3,5,6,9,11,16,22,28).…”

Conjunctival endogenous microbiota in patients submitted to cataract surgery

“…Several authors investigated the antimicrobial susceptibility of microorganisms isolated from ocular infection with different patterns of sensitivity occurring (9,20,23,26,32,33), but little information is available in our country (25). The purpose of the present study was to evaluate the conjunctival aerobic microbiota of individuals submitted to cataract surgery and in vitro antimicrobial susceptibility of the isolates by using swabs and intraocular lenses for material collection.…”

In Vitro Pharmacodynamic Evaluation of the Mutant Selection Window Hypothesis Using Four Fluoroquinolones against Staphylococcus aureus

“…Bacterial resistance has been studied infrequently using these models. Limited observations reported from earlier timekill studies (3,8,(21)(22)(23) precluded delineation of relationships of the area under the concentration-time curve (AUC)/MIC ratio with resistance because the ranges of the simulated AUCto-MIC ratios were too narrow. In fact, the first attempts to relate resistance to the AUC/MIC or peak concentration (C max )/MIC ratio were reported quite recently from studies that declared resistance analysis as a primary goal (1, 7, 17, 18, 20, 25-27, 30, 33, 34; A. MacGowan and K. Bowker, Abstr.…”