Ecological effects of linezolid versus amoxicillin/clavulanic acid on the normal intestinal microflora

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.