While antibiotic use is a risk factor of carbapenemase-producing Enterobacteriaceae (CPE) acquisition, the importance of timing of antibiotic administration relative to CPE exposure remains unclear. In a murine model of gut colonization by New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Klebsiella pneumoniae, a single injection of clindamycin within at most 1 week before or after CPE exposure induced colonization persisting up to 100 days. The timing of antibiotic administration relative to CPE exposure may be relevant to infection control and antimicrobial stewardship approaches. KEYWORDS Klebsiella pneumoniae, NDM-1, carbapenemase, gut microbiota, murine model C arbapenemase-producing Enterobacteriaceae (CPE) are an emerging public health issue, considered a critical priority by the World Health Organization (1). Among CPE, New Delhi metallo-beta-lactamase-1 (NDM-1)-producing Enterobacteriaceae are particularly preoccupying. Indeed, NDM-1 confers resistance to most -lactams, including carbapenems, and has spread worldwide (2), raising fears of severe infections without therapeutic options (3).In the hospital setting, contact with a CPE-colonized patient or prior antibiotic use are major risk factors for CPE acquisition (4, 5). Among antibiotics, antianaerobes (e.g., piperacillin-tazobactam or clindamycin) seem particularly at risk (6, 7).While antibiotics are a known risk factor, the role of the timing of CPE exposure relative to antibiotic administration is unclear. We describe here a murine model of gut colonization with NDM-1-producing Klebsiella pneumoniae following a single administration of clindamycin and assess the effects of timing of clindamycin administration relative to CPE exposure on effective CPE colonization.The French Ethical Committee for Animal Experimentation approved this study (APAFIS #7166). Seven-week-old C57BL/6 male mice housed under specific-pathogen-free conditions and a clinical isolate of Klebsiella pneumoniae-producing NDM-1-carbapenemase were used (8).First, we validated the murine model of CPE gut colonization. Mice were divided into four groups with or without 24-h CPE exposure in drinking water (10 7 CFU/ml at day 0) and/or intraperitoneal clindamycin (200 g) (Fig. 1). The CPE load was evaluated by plating stool samples onto selective medium (lysogeny broth agar with 32 mg/liter cefotaxime and 6 mg/liter vancomycin). In mice exposed to both CPE and clindamycin,
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