Pharmacokinetics and serum bactericidal activities of quinolones in combination with clindamycin, metronidazole, and ornidazole

Abstract

To enhance the antimicrobial spectrum of the quinolones against anaerobic organisms and gram-positive bacteria, we investigated in two studies the parenteral combinations of ciprofloxacin (200 mg) and ofloxacin (200 mg) with metronidazole (500 mg) or clindamycin (600 mg) and the oral combinations of enoxacin (400 mg) and fleroxacin (400 mg) with metronidazole (400 mg), clindamycin (300 mg), or ornidazole (500 mg) (only with fleroxacin). The pharmacokinetics and serum bactericidal activities (SBAs) against 5 aerobic and 2 anaerobic species (total, 58 strains) were determined in two groups of 10 healthy volunteers by using a randomized crossover study design. The additions of metronidazole, clindamycin, and ornidazole did not affect the pharmacokinetics of the quinolones. The combination of clindamycin with ciprofloxacin, ofloxacin, and, to a lesser extent, fleroxacin resulted in an increase of the SBA against gram-positive strains (mean peak titers): Staphylococcus aureus, ciprofloxacin alone, 1:5.5; ciprofloxacin-clindamycin, 1:19.9; ofloxacin alone, 1:3.6; ofloxacin-clindamycin, 1:17.5; fleroxacin alone, 1:4.3; fleroxacin-clindamycin, 1:8.1; Streptococcus pneumoniae (fleroxacin and enoxacin were not tested), ciprofloxacin alone, 1:2.0; ciprofloxacin-clindamycin, 1:53; ofloxacin alone, 1:2.6; and ofloxacin-clindamycin, 1:49.2. The high SBA of quinolones against gram-negative bacteria was not affected by the combinations; however, relatively low activities against Pseudomonas aeruginosa were detected. In general, against anaerobic bacteria, low bactericidal activities were determined in both studies (mean peak titers ranged from 1:2

Comparative serum bactericidal activities of three doses of ciprofloxacin administered intravenously

“…DISCUSSION We elected to recruit hospitalized patients for our study because they better represent the population in which intravenous ciprofloxacin might be used than do young volunteers. The pharmacokinetic values generated are similar to those previously reported in some studies (1,11) and differ from those described in others (20). The higher Cm.…”

Comparative Serum Bactericidal Activity against <i>Pseudomonas aeruginosa </i>of Six Antipseudomonal Agents

“…It is not surprising, therefore, that others [18,22] obtained even better SBA with the same dose of ceftazidime and also demon strated the superiority of this agent over other antipseudomonal drugs. Ciprofloxacin dis played the second best bactericidal activity, yet a short-lived one, with results similar to those previously reported [17,19], Although 200 mg was the standard intravenous dose re commended in the early period, ex vivo and clinical data subsequently showed that a dose of 400 mg was more appropriate for infec tions caused by P. aeruginosa [23], Imipenem and aztreonam appeared to have a mediocre antipseudomonal activity; similar results were obtained by other authors [8,22], In agreement with previous results [8], the pri mary antipseudomonal agents, gentamicin and piperacillin, showed the poorest bacteri cidal efficacy, despite the optimal serum con centrations achieved. Indeed, although both gentamicin and piperacillin had good in vitro activity against P. aeruginosa, numerous ther apeutic failures were reported with the emer gence of resistant organisms during mono therapy with these agents [ 1 ].…”

Fluoroquinolones and Anaerobes

“…Boeckh et al [44] found no beneficial effect of the combination of ciprofloxacin or ofloxacin with metronidazole and clindamycin in serum against B. fragilis and B. thetaiotaomicron. Goldstein and Citron [45], using a microbroth dilution method, found that the effect of the combination of ofloxacin and metronidazole was generally additive or indifferent against anaerobic bacteria.…”