Editors' ChoiceAntibiotics

Too Much of a Good Thing?

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Science Translational Medicine  05 Jan 2011:
Vol. 3, Issue 64, pp. 64ec3
DOI: 10.1126/scitranslmed.3002074

Antibiotics remain the cornerstone of treatment for infectious diseases, but their excessive use has resulted in the emergence of resistant strains of bacteria—an ever-increasing problem among hospitalized patients. The inappropriate use of antibiotics can also cause severe bloodstream infections and a potentially devastating condition known as pseudomembranous colitis. These complications are thought to arise from alterations in the microbial flora that populate intestinal mucosal surfaces, leading to the overgrowth of antibiotic-resistant bacteria such as vancomycin-resistant Enterococcus (VRE), Acinetobacter species, Pseudomonas aeruginosa, and Clostridium difficile. Using high-throughput DNA sequencing technologies, Ubeda et al. now characterize the antibiotic-induced changes in the intestinal flora as well as the effects of these changes on intestinal colonization and bloodstream invasion by VRE.

The researchers treated mice with various antibiotic regimens and then harvested stool samples and intestinal contents for analysis. They found that antibiotic treatment decreased total bacterial density and dramatically altered the bacterial composition of the small and large intestines. The frequency of bacteria from the Clostridium and Enterococcus families significantly increased, an effect that persisted even after cessation of therapy. Concomitantly, populations that prevent VRE colonization, such as the Lactobacilli and Bacteroides species, were lost and did not recover for up to two months after cessation of antibiotic treatment. Lastly, in human patients undergoing bone marrow transplantation, the predominance of Enterococcus in the intestinal flora preceded bloodstream infection with VRE.

The findings of this study demonstrate the dramatic changes in microbial diversity after antibiotic therapy, with loss of normal bacterial populations and overwhelming expansion of resistant strains such as VRE. These alterations in the intestinal flora not only predispose patients to invasive bloodstream infections but have also been implicated in the pathogenesis of obesity and inflammatory bowel diseases. Because intestinal colonization by pathogenic strains of bacteria precedes their invasion into the bloodstream, using high-throughput DNA sequencing technologies to characterize the microbial composition in the intestines may help us to identify patients at risk for developing systemic infections.

C. Ubeda et al., Vancomycin-resistant Enterococcus domination of intestinal microbiota is enabled by antibiotic treatment in mice and precedes bloodstream invasion in humans. J. Clin. Invest. 120, 4332–4341 (2010). [Full Text]

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