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JAC Advance Access published online on July 12, 2006
Journal of Antimicrobial Chemotherapy, doi:10.1093/jac/dkl281
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© The Author 2006. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org
Received February 16, 2006
Revised May 31, 2006
Accepted June 14, 2006

Original article

Effect of dalbavancin on the normal intestinal microflora

Carl Erik Nord 1 *, Gundars Rasmanis 1, and Elisabeth Wahlund 1

1 Department of Laboratory Medicine, Karolinska University Hospital, Karolinska Institute, SE-141 86 Stockholm, Sweden

* To whom correspondence should be addressed.
Carl Erik Nord, E-mail: carl.erik.nord{at}ki.se


  Abstract

Objectives: 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 t1/2 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.

Methods: 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.

Results: 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.

Conclusions: Dalbavancin has no major ecological effect on the human normal intestinal microflora.

Keywords: antibiotics; clinical trials; pharmaceutical products.
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[Abstract] [Full Text] [PDF]


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