Effect of Ceftaroline on Normal Human Intestinal Microflora

Abstract

Ceftaroline is a new broad-spectrum cephalosporin being developed for the treatment of serious bacterial infections, including those caused by aerobic Gram-positive and Gram-negative bacteria. The purpose of the present study was to investigate the effect of administration of ceftaroline on the intestinal flora of healthy subjects. Twelve healthy subjects (6 males and 6 females), 20 to 41 years of age, received ceftaroline (600 mg) by intravenous infusion every 12 h (q12h) for 7 days. Plasma and feces were collected for determination of ceftaroline concentration and analysis of fecal flora. Fecal specimens were cultured on nonselective and selective media. Different colony types were counted, isolated in pure culture, and identified to the genus level. All new strains of colonizing bacteria were tested for susceptibility to ceftaroline. The concentrations of ceftaroline in plasma were as follows: on day 2, 17.5 to 34.8 mg/liter; on day 5, 19.7 to 33.2 mg/liter; and on day 7, 18.0 to 29.8 mg/liter. No ceftaroline concentrations were found on day ؊1, 9, 14, or 21. No measurable concentrations in feces were found on day ؊1, 2, 5, 7, 9, 14, or 21. There was a minor impact on the numbers of Escherichia coli strains, while the numbers of enterococci and Candida albicans strains were not affected. There were moderate decreases in the numbers of bifidobacteria and lactobacilli during the first 7 days, while the numbers of clostridia increased during the same period. No impact on the numbers of Bacteroides bacteria was noticed. No new colonizing aerobic or anaerobic bacteria resistant to ceftaroline (MIC > 4 mg/liter) were found. Ceftaroline had no significant ecological impact on the human intestinal microflora.

Ecological Effect of Ceftaroline-Avibactam on the Normal Human Intestinal Microbiota

“…The MIC value for the C. difficile strain was 1 mg/liter. In the previous study, no new colonizing aerobic and anaerobic bacteria resistant to ceftaroline (MIC, Ն4 mg/liter) were found (19). In the current study, new colonizing aerobic and anaerobic bacteria resistant to ceftaroline-avibactam (MIC, Ն1 mg/liter) were found.…”

“…Toxigenic C. difficile strains were found in 5 of the 12 volunteers; in 4 of these volunteers, loose stools were reported as adverse events (21). In the previous ceftaroline study, six toxigenic C. difficile strains were isolated from 2 subjects, and the MICs were 4 to 8 mg/liter (19). No clinical symptoms were observed in the 2 subjects (19).…”

“…Usually, ␤-lactamase inhibitors have no antibacterial activity of their own (18). The ecological impact of ceftaroline was studied by Panagiotidis et al (19), and no fecal concentration of ceftaroline was found in the feces in healthy volunteers. There was a minor impact on the numbers of E. coli microorganisms, while the numbers of enterococci and Candida albicans microorganisms were not affected.…”

“…In the previous ceftaroline study, six toxigenic C. difficile strains were isolated from 2 subjects, and the MICs were 4 to 8 mg/liter (19). No clinical symptoms were observed in the 2 subjects (19).…”

“…were resistant to ceftaroline-avibactam (MIC, Ն1 to Ͼ256 mg/liter). In the previous study, all B. fragilis group strains were ␤-lactamase producers and resistant to ceftaroline (MIC, Ն64 mg/liter) (19).…”