In a study of 40 methicillin-resistant Staphylococcus aureus (MRSA) carriers, hand contamination was equally likely after contact with commonly examined skin sites and commonly touched environmental surfaces in patient rooms (40% vs 45%). These findings suggest that contaminated surfaces may be an important source of MRSA transmission.

Antibiotics excreted into the intestinal tract may disrupt the microbiota that provide colonization resistance against enteric pathogens and alter normal metabolic functions of the microbiota. Many of the bacterial metabolites produced in the intestinal tract are absorbed systemically and excreted in urine. Here, we used a mouse model to test the hypothesis that alterations in levels of targeted bacterial metabolites in urine specimens could provide useful biomarkers indicating disrupted or intact colonization resistance. To assess in vivo colonization resistance, mice were challenged with Clostridium difficile spores orally 3, 6, and 11 days after the completion of 2 days of treatment with piperacillin-tazobactam, aztreonam, or saline. For concurrent groups of antibiotic-treated mice, urine samples were analyzed by using liquid chromatography-tandem mass spectrometry (LC-MS/MS) to quantify the concentrations of 11 compounds targeted as potential biomarkers of colonization resistance. Aztreonam did not affect colonization resistance, whereas piperacillin-tazobactam disrupted colonization resistance 3 days after piperacillintazobactam treatment, with complete recovery by 11 days after treatment. Three of the 11 compounds exhibited a statistically significant and Ͼ10-fold increase (the tryptophan metabolite N-acetyltryptophan) or decrease (the plant polyphenyl derivatives cinnamoylglycine and enterodiol) in concentrations in urine 3 days after piperacillin-tazobactam treatment, followed by recovery to baseline that coincided with the restoration of in vivo colonization resistance. These urinary metabolites could provide useful and easily accessible biomarkers indicating intact or disrupted colonization resistance during and after antibiotic treatment. KEYWORDS intestinal microbiotaT he gastrointestinal tract of adult mammals is inhabited by a complex microbial community that includes hundreds of bacterial species (1). These organisms complement host physiology by providing an array of metabolic functions that benefit the host (e.g., digestion of complex polysaccharides and proteins) (1-4). The indigenous microbiota of the colon also provide an important host defense, termed colonization resistance, by inhibiting the growth of potentially pathogenic microorganisms such as Clostridium difficile (5,6). Antibiotics that are excreted into the intestinal tract may suppress the microbiota and disrupt bacterial metabolic functions and colonization resistance (5-9). We demonstrated previously that clindamycin or piperacillintazobactam treatment of mice resulted in the disruption of colonization resistance

Antibiotics disrupt the intestinal microbiota, rendering patients vulnerable to colonization by exogenous pathogens. Intermicrobial interactions may attenuate this effect. Incubation with ceftriaxone-resistant, ccrA-positive, ␤-lactamase-producing Bacteroides strains raised the minimum bactericidal concentration of ceftriaxone required to kill a susceptible Escherichia coli strain (mean change, <0.25 to 29 mg/liter; P ‫؍‬ 0.009); incubation with ceftriaxone-resistant but non-␤-lactamase-producing Bacteroides strains had no effect. The production of ␤-lactamase by common members of the intestinal microbiota (Bacteroides) can protect susceptible fellow commensals from ␤-lactams. The indigenous anaerobic microbiota of the lower intestinal tract remains a crucial mammalian host defense against colonization by exogenous, potentially pathogenic microorganisms (1-3). This defense mechanism is termed colonization resistance and may be abolished in hospitalized patients by the administration of antibiotic therapy. Antibiotics, including ␤-lactam antibiotics, may disrupt the intestinal microbiota, rendering patients susceptible to colonization or infection with nosocomial pathogens.We previously demonstrated in ␤-lactam-treated mice that oral recombinant proteolysis-resistant ␤-lactamase enzymes that inactivate ␤-lactams can preserve gut colonization resistance against multiple nosocomial pathogens, including vancomycinresistant Enterococcus (VRE), extended-spectrum ␤-lactamaseproducing Klebsiella pneumoniae, and Clostridium difficile (4-6), via intraintestinal degradation of excreted antibiotic by intraluminal ␤-lactamases. This strategy holds promise for the prevention of pathogen colonization in patients treated with parenteral antibiotics, as antibiotic degradation within the colonic lumen does not impact systemic concentrations (7). We also demonstrated that, despite their receipt of parenteral ␤-lactams, mice intestinally colonized with a ␤-lactamase-producing member of the commensal microbiota (Bacteroides thetaiotaomicron) preserved colonization resistance against VRE and C. difficile (8). However, the genetics of ␤-lactam resistance in the protective Bacteroides species in this study were not known, and a comparator anaerobe was not studied. Here, we hypothesized that ceftriaxone-resistant Bacteroides species producing the broad-spectrum metallo-␤-lactamase CcrA would protect ␤-lactam-susceptible members of the microbiota from the ␤-lactam ceftriaxone in vitro, while ceftriaxone-resistant (but non-␤-lactamase-producing) Bacteroides species would not.(Portions of this study were previously presented in abstract form at the 51st Interscience Conference on Antimicrobial Agents and Chemotherapy, Chicago, IL, 17 to 20 September 2011.)Bacterial strains. To test the protection of a clinical strain of ceftriaxone-susceptible Escherichia coli (chosen as a representative member of the human gut microbiome that can be grown on a medium different than that for Bacteroides) from ceftriaxone, four highly cephalosporin-resistan...