The pharmacokinetics of gatifloxacin (400 mg orally) and the influence of the antacid aluminum magnesium hydroxide (20 ml of Maalox 70) on the bioavailability of gatifloxacin in 24 healthy volunteers were assessed. In an open, randomized, six-period crossover study, the volunteers received either gatifloxacin alone (treatments A and D); aluminum magnesium hydroxide concomitant with gatifloxacin (treatment C); or aluminum magnesium hydroxide 2 h before (treatment B), 2 h after (treatment E), or 4 h after gatifloxacin administration (treatment F). Gatifloxacin concentrations were measured by a validated bioassay and high-performance liquid chromatography. Pharmacokinetics of a single 400-mg dose of gatifloxacin alone were characterized as follows (mean ± standard deviation): peak concentration (C max), 3.8 ± 0.5 (treatment A) and 3.4 ± 0.9 (treatment D) μg/ml; time toC max, 1.4 ± 0.8 (treatment A) and 1.7 ± 0.7 (treatment D) h; area under the curve from time zero to infinity (AUC0–∞), 33.5 ± 5.9 (treatment A) and 31.4 ± 3.4 (treatment D) μg · h/ml; urine recovery, (83 ± 6)% (treatment A) and (84 ± 8)% (treatment D). Comparison of the results obtained by bioassay showed a good correlation. Aluminum magnesium hydroxide administration 2 h before (treatment B) or concomitant with (treatment C) gatifloxacin decreased the C max by 45% (2.1 ± 1.2 μg/ml) or even 68% (1.2 ± 0.4 μg/ml) highly significantly (P < 0.01). AUC0–∞ was significantly reduced from 33.5 ± 5.9 to 19.4 ± 6.9 μg · h/ml (by 42%) or even to 11.9 ± 3.3 μg · h/ml (by 64%) (P < 0.01). If aluminum magnesium hydroxide was given 2 h after gatifloxacin (treatment E), there was no significant reduction of concentration in serum but AUC0–∞ was significantly reduced from 31.4 ± 3.4 to 25.9 ± 5.3 μg · h/ml (18%) (P < 0.01). Aluminum magnesium hydroxide given 4 h after gatifloxacin (treatment F) showed no influence on the gatifloxacin pharmacokinetics. Therefore, the optimal time between gatifloxacin application and the intake of an aluminum-containing antacid should be 4 h.

Twelve healthy subjects (6 females, 6 males; age range 18-40 y) participated in this trial. Linezolid was given as 600 mg tablets b.i.d. for 7 d and amoxicillin/clavulanic acid as 1000 mg tablets o.d. for 7 d. The washout period between the administration of the 2 antibacterial agents was 4 weeks. Faecal samples were collected prior to administration (Days -2 and -1), during administration (Days 4 and 8) and after administration (Days 14, 21 and 35) for microbiological analyses. The samples were diluted in pre-reduced media and inoculated aerobically and anaerobically on non-selective and selective media. Different colony types were identified to genus level by morphological, biochemical and molecular analyses. During the administration of linezolid, enterococci in the intestinal aerobic microflora were markedly suppressed while Klebsiella organisms increased in number. In the anaerobic microflora, the numbers of bifidobacteria, lactobacilli, clostridia and Bacteroides decreased markedly while no impact on the other anaerobic bacteria was observed. The microflora was normalized in all volunteers after 35 d. Amoxicillin/clavulanic acid administration caused increased numbers of enterococci and Escherichia coli in the aerobic intestinal microflora while numbers of bifidobacteria, lactobacilli and clostridia decreased significantly. Clostridium difficile strains were recovered from 3 of the volunteers. At the last visit, the intestinal microflora of the volunteers had returned to normal levels. The administration of linezolid mainly had an impact on the gram-positive bacteria and linezolid thus had an ecological profile different from that of amoxicillin/clavulanic acid.

A multiple-dose, randomized, double-blind, controlled, cross-over trial was performed in 12 healthy male subjects in order to investigate the effect of a 7-day treatment with moxifloxacin (400 mg orally, once daily) versus clarithromycin (500 mg orally, twice daily) on the normal oropharyngeal microflora. Moxifloxacin caused significant reductions in levels of alpha-streptococci and Neisseria cocci during the treatment period, while the numbers of gram-negative anaerobic bacteria increased markedly during moxifloxacin administration. Clarithromycin administration caused a suppression of micrococci and corynebacteria, while no significant changes were recorded in the anaerobic microflora. No new colonizing moxifloxacin-resistant strains were isolated during the investigation period.

Our study suggests a favorable interaction between trovafloxacin and cefepime. This combination showed more synergistic bactericidal activity against most of the test strains compared to the combination of trovafloxacin and amikacin. However, for P. aeruginosa, the bactericidal activity of cepefime alone was higher than that of the combination with trovafloxacin.