title: Activity of antimicrobial combinations against KPC-2-producing Klebsiella pneumoniae in a rat model and time-kill assay.
abstract: This study evaluated the efficacy of tigecycline (TIG), polymyxin B (PMB), and meropenem (MER) in 80 rats challenged with Klebsiella pneumoniae carbapenemase (KPC)-producing K. pneumoniae infection. A time-kill assay was performed with the same strain. Triple therapy and PMB+TIG were synergistic, promoted 100% survival, and produced negative peritoneal cultures, while MER+TIG showed lower survival and higher culture positivity than other regimens (P = 0.018) and was antagonistic. In vivo and in vitro studies showed that combined regimens, except MER+TIG, were more effective than monotherapies for this KPC-producing strain.
authors.affiliation: Internal Medicine Postgraduate Training, Universidade Federal do Paraná, Curitiba, Brazil Medicine Department, Universidade Estadual de Ponta Grossa, Ponta Grossa, Brazil paulavmtoledo@yahoo.com.br.
authors.forename: Paula Virginia Michelon
authors.initials: PV
authors.lastname: Toledo
authors.affiliation: Medicine Department, Universidade Estadual de Ponta Grossa, Ponta Grossa, Brazil Anatomy Department, Universidade Federal do Paraná, Curitiba, Brazil.
authors.forename: Ayrton Alves
authors.initials: AA
authors.lastname: Aranha Junior
authors.affiliation: Bacteriology Section, Laboratório Central de Saúde Pública do Estado LACEN-PR, Curitiba, Brazil.
authors.forename: Lavinia Nery
authors.initials: LN
authors.lastname: Arend
authors.affiliation: Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Vanessa
authors.initials: V
authors.lastname: Ribeiro
authors.affiliation: Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Alexandre Prehn
authors.initials: AP
authors.lastname: Zavascki
authors.affiliation: Internal Medicine Postgraduate Training, Universidade Federal do Paraná, Curitiba, Brazil Division of Infectious and Parasitic Diseases, Hospital Universitário Evangélico de Curitiba, Curitiba, Brazil.
authors.forename: Felipe Francisco
authors.initials: FF
authors.lastname: Tuon
mesh_terms: D000818:Animals; D000900:Anti-Bacterial Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D001202:Ascitic Fluid / Q000382:microbiology; D015169:Colony Count, Microbial; D004338:Drug Combinations; D004347:Drug Interactions; D004357:Drug Synergism; D005260:Female; D053208:Kaplan-Meier Estimate; D007710:Klebsiella Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D007711:Klebsiella pneumoniae / Q000187:drug effects* / Q000235:genetics; D008297:Male; D008826:Microbial Sensitivity Tests; D051381:Rats; D017208:Rats, Wistar; D001618:beta-Lactamases / Q000235:genetics*
chemical_list: D000900:Anti-Bacterial Agents; D004338:Drug Combinations; C491478:beta-lactamase KPC-2; D001618:beta-Lactamases