Effect of dalbavancin on the normal intestinal microflora

Abstract

Dalbavancin is a new lipoglycopeptide antibiotic active in vitro against most Gram-positive bacteria. It is administered parenterally as a weekly regimen, is eliminated both in urine and faeces, and has t(1/2) in plasma of 8.5 days. Investigating the impact of antibiotics on endogenous microflora is important since alteration of the balance may facilitate colonization by new potentially pathogenic strains or enable microorganisms in the normal flora to develop resistance. The purpose of the present study was to investigate the effect of administration of dalbavancin on the intestinal flora of healthy subjects. Six women and six men, 18-40 years, received a single 30 min intravenous infusion of 1 g dalbavancin. Plasma and faeces were collected over several weeks for determination of dalbavancin concentration and analysis of faecal flora. 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 colonizing bacteria were tested for susceptibility to dalbavancin. Plasma dalbavancin concentrations at 2, 21 and 60 days after administration were 35.8-208.7, 3.9-22.1 and 0.5-2.9 mg/L, respectively. The faecal concentrations of dalbavancin were 6.8-73.4 mg/kg on day 5 and 7.4-26.4 mg/kg on day 14. Dalbavancin was not detectable in faeces on day 60. There was some impact on numbers of enterococci and Escherichia coli and no changes in numbers of lactobacilli, clostridia and bacteroides. No Clostridium difficile strains were recovered. No new colonizing aerobic and anaerobic bacteria resistant to dalbavancin were found. Dalbavancin has no major ecological effect on the human normal intestinal microflora.