Effect of ceftobiprole on the normal human intestinal microflora

Ceftobiprole is a new broad-spectrum pyrrolidinone cephem active against meticillin-resistant Staphylococcus aureus, vancomycin-resistant Enterococcus faecalis and Gram-negative bacteria such as Enterobacteriaceae and Pseudomonas spp. The purpose of the present study was to investigate the effect of administration of ceftobiprole on the normal intestinal microflora. Twelve healthy subjects (six males and six females) aged 20–31 years received ceftobiprole 500 mg by intravenous infusion every 8 h for 7 days. Plasma samples were collected on Days −1, 1, 4, 7, 10, 14 and 21 for determination of drug concentration by biological and chemical methods. Faecal samples were collected on Days −1, 2, 4, 7, 10, 14 and 21. For analysis of the microflora, faecal specimens were cultured on non-selective and selective media. Different colony types were counted, isolated in pure culture and identified to genus level. All new colonising aerobic and anaerobic bacteria were tested for susceptibility to ceftobiprole. Plasma concentrations of ceftobiprole 10 min after completion of infusion were as follows: Day 1, 14.7–23.6 mg/L; Day 4, 15.9–24.5 mg/L; and Day 7, 15.9–23.9 mg/L. No ceftobiprole was detected in plasma on Days −1, 10, 14 and 21. No measurable concentrations of ceftobiprole were found in faeces on Days −1, 2, 4, 7, 10, 14 and 21. There were minor changes in the numbers of enteric bacteria, enterococci and Candida albicans and there were moderate changes in the numbers of bifidobacteria, lactobacilli, clostridia and Bacteroides spp. during the same period. No Clostridium difficile strains or toxins were found. No new colonising aerobic and anaerobic bacteria with ceftobiprole minimum inhibitory concentrations of ≥4 mg/L were found. Ceftobiprole had no significant ecological impact on the human intestinal microflora.