caa a22 4500 397593090 CHVBK 20180308164944.0 cr unu---uuuuu 161202e199604 xx s 000 0 eng 10.1093/jac/37.4.703 doi (NATIONALLICENCE)oxford-10.1093/jac/37.4.703 A pharmacodynamic evaluation of ciprofloxacin and ofloxacin against two strains of Pseudomonas aeruginosa [Elektronische Daten] [Karl J. Madaras-Kelly, Alison J. Larsson, John C. Rotschafer] 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. © 1996 The British Society for Antimicrobial Chemotherapy Original articles nationallicence Madaras-Kelly Karl J. College of Pharmacy, Idaho State University Pocatello, ID; USA aut Larsson Alison J. St. Paul-Ramsey Medical-Center St. Paul, MN; USA aut Rotschafer John C. St. Paul-Ramsey Medical-Center St. Paul, MN; USA aut Journal of Antimicrobial Chemotherapy Oxford University Press 37/4(1996-04), 703-710 0305-7453 37:4<703 1996 37 jac https://doi.org/10.1093/jac/37.4.703 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1093/jac/37.4.703 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Madaras-Kelly Karl J. College of Pharmacy, Idaho State University Pocatello, ID; USA aut NATIONALLICENCE 700 1- Larsson Alison J. St. Paul-Ramsey Medical-Center St. Paul, MN; USA aut NATIONALLICENCE 700 1- Rotschafer John C. St. Paul-Ramsey Medical-Center St. Paul, MN; USA aut NATIONALLICENCE 773 0- Journal of Antimicrobial Chemotherapy Oxford University Press 37/4(1996-04), 703-710 0305-7453 37:4<703 1996 37 jac Metadata rights reserved CC BY-NC-4.0 http://creativecommons.org/licenses/by-nc/4.0 nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-oxford