Comparison of the bactericidal activity of trovafloxacin and ciprofloxacin, alone and in combination with cefepime, against Pseudomonas aeruginosa.
BACKGROUND
Although ciprofloxacin exhibits more intense microbiological activity against Pseudomonas aeruginosa than does trovafloxacin, the clinical relevance of this observation remains questionable, particularly when the agents are combined with another antipseudomonal agent.


METHODS
To evaluate this further, we conducted a four-way crossover trial to compare the bactericidal activities of ciprofloxacin and trovafloxacin, alone and in combination with cefepime, against three clinical isolates of P. aeruginosa. Healthy subjects received the following regimens, dosed to steady state: trovafloxacin 300 mg/24 h; ciprofloxacin 400 mg/12 h; trovafloxacin 300 mg/24 h plus cefepime 2 g/12 h, and ciprofloxacin 400 mg/12 h plus cefepime 2 g/12 h. Serum bactericidal titers were performed with each regimen.


RESULTS
As monotherapy, the area under the bactericidal curve for ciprofloxacin exceeded that of trovafloxacin for all isolates. No significant difference in the overall degree of bactericidal activity was noted for two of three P. aeruginosa isolates for the combination regimens. Additionally, both combination regimens provided bactericidal activity for 100% of the dosing interval for all isolates.


CONCLUSIONS
These results indicate that, while in vitro differences exist among these quinolones for P. aeruginosa, when a fluoroquinolone is combined with a beta-lactam, this is likely to be of little clinical significance.
McNabb
J
J
Department of Pharmacy, Hartford Hospital, Hartford, CT 06102, USA.
Quintiliani
R
R
Nightingale
C H
CH
Nicolau
D P
DP
D000328:Adult; D000704:Analysis of Variance; D000890:Anti-Infective Agents / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D019540:Area Under Curve; D000077723:Cefepime; D002511:Cephalosporins / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D002939:Ciprofloxacin / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D018592:Cross-Over Studies; D004359:Drug Therapy, Combination / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D005260:Female; D024841:Fluoroquinolones; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D009287:Naphthyridines / Q000009:adverse effects / Q000493:pharmacokinetics / Q000494:pharmacology*; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D015610:Serum Bactericidal Test
D000890:Anti-Infective Agents; D002511:Cephalosporins; D024841:Fluoroquinolones; D009287:Naphthyridines; D002939:Ciprofloxacin; D000077723:Cefepime; C080163:trovafloxacin