Wiskirchen, Dora E. Nordmann, Patrice Crandon, Jared L. Nicolau, David P. 2014-02-19 Doripenem and ertapenem have demonstrated efficacy against several NDM-1- producing isolates <em>in vivo</em>, despite having high MICs. In this study, we sought to further characterize the efficacy profiles of humanized regimens of standard (500 mg given every 8 h) and high-dose, prolonged infusion of doripenem (2 g given every 8 h, 4-h infusion) and 1 g of ertapenem given intravenously every 24 h and the comparator regimens of ceftazidime at 2 g given every 8 h (2-h infusion), levofloxacin at 500 mg every 24 h, and aztreonam at 2 g every 6 h (1-h infusion) against a wider range of isolates in a murine thigh infection model. An isogenic wild-type strain and NDM-1-producing Klebsiella pneumoniae and eight clinical NDM-1-producing members of the family Enterobacteriaceae were tested in immunocompetent- and neutropenic-mouse models. The wild-type strain was susceptible to all of the agents, while the isogenic NDM-1-producing strain was resistant to ceftazidime, doripenem, and ertapenem. Clinical NDM-1-producing strains were resistant to nearly all five of the agents (two were susceptible to levofloxacin). In immunocompetent mice, all of the agents produced ≥1-log₁₀ CFU reductions of the isogenic wild-type and NDM-1- producing strains after 24 h. Minimal efficacy of ceftazidime, aztreonam, and levofloxacin against the clinical NDM-1-producing strains was observed. However, despite <em>in vitro</em> resistance, ≥1-log₁₀ CFU reductions of six of eight clinical strains were achieved with high-dose, prolonged infusion of doripenem and ertapenem. Slight enhancements of doripenem activity over the standard doses were obtained with high-dose, prolonged infusion for three of the four isolates tested. Similar efficacy observations were noted in neutropenic mice. These data suggest that carbapenems are a viable treatment option for infections caused by NDM-1-producing Enterobacteriaceae. application/pdf https://folia.unifr.ch/global/documents/303549 https://folia.unifr.ch/documents/303549/files/nor_veh.pdf eng info:eu-repo/semantics/altIdentifier/doi/10.1128/AAC.01946-13 info:eu-repo/semantics/openAccess License undefined Antimicrobial Agents and Chemotherapy. - 2014, vol. 58, no. 3, p. 1671-1677 info:eu-repo/classification/udc/61 <i>In Vivo</i> Efficacy of Human Simulated Regimens of Carbapenems and Comparator Agents against NDM-1-Producing Enterobacteriaceae http://purl.org/coar/resource_type/c_6501