title: Colistin-resistant Enterobacteriaceae infections: clinical and molecular characterization and analysis of in vitro synergy.
abstract: We described 27 polyclonal colistin-resistant Enterobacteriaceae (MIC 4-16 μg/mL) infections (12 pneumonia, 12 urinary tract infection (UTI), two Bacteremia, and one skin/soft tissue infection) in which 74% harbored KPC. The isolates were polyclonal, 6 STs were identified and the colistin resistance was due to chromosome mutations. Eight patients with UTI received monotherapy, and combination therapy was given to 19 patients. Overall mortality was 37%. In vitro synergy using time-kill assay was observed in 14 of 19 (74%) isolates tested; the synergistic effect was observed for almost all isolates for the combination of three drugs: colistin, amikacin, and tigecycline. The Kaplan-Meier survival curve showed no significant difference comparing combination therapy with 2, 3, or more drugs and risk factors associated with death were dialysis and shock. These findings reinforce the fact that colistin in combination with other classes of drugs can be useful in treating infections caused by colistin-resistant CRE.
authors.affiliation: Infection Control Committee, Intensive Care Unit, Department of Clinical Medicine, State University of Londrina, Londrina, Paraná, Brazil.
authors.forename: Claudia M D
authors.initials: CM
authors.lastname: de Maio Carrillho
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Juliana J
authors.initials: JJ
authors.lastname: Gaudereto
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Roberta Cristina Ruedas
authors.initials: RC
authors.lastname: Martins
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Victor Augusto Camarinha
authors.initials: VA
authors.lastname: de Castro Lima
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Larissa M
authors.initials: LM
authors.lastname: de Oliveira
authors.affiliation: Department of Statistics, State University of Londrina, Paraná, Brazil.
authors.forename: Mariana R
authors.initials: MR
authors.lastname: Urbano
authors.affiliation: University Hospital, Londrina, Paraná, Brazil; Hospital do Cancer de Londrina, Brazil.
authors.forename: Jamile S
authors.initials: JS
authors.lastname: Perozin
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil.
authors.forename: Anna Sara
authors.initials: AS
authors.lastname: Levin
authors.affiliation: University of São Paulo Medical School, São Paulo, Brazil. Electronic address: costasilviaf@ig.com.br.
authors.forename: Silvia F
authors.initials: SF
authors.lastname: Costa
mesh_terms: D000583:Amikacin / Q000627:therapeutic use*; D000900:Anti-Bacterial Agents / Q000494:pharmacology*; D001426:Bacterial Proteins / Q000235:genetics; D003091:Colistin / Q000627:therapeutic use*; D024901:Drug Resistance, Multiple, Bacterial / Q000235:genetics; D004357:Drug Synergism; D004359:Drug Therapy, Combination; D004755:Enterobacteriaceae / Q000187:drug effects* / Q000235:genetics / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology / Q000401:mortality; D005260:Female; D006801:Humans; D053208:Kaplan-Meier Estimate; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D008911:Minocycline / Q000031:analogs & derivatives* / Q000627:therapeutic use; D011014:Pneumonia / Q000188:drug therapy / Q000382:microbiology; D011446:Prospective Studies; D018461:Soft Tissue Infections / Q000188:drug therapy / Q000382:microbiology; D000078304:Tigecycline; D014552:Urinary Tract Infections / Q000188:drug therapy / Q000382:microbiology; D001618:beta-Lactamases / Q000235:genetics
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D000078304:Tigecycline; D000583:Amikacin; D001618:beta-Lactamases; C063912:carbapenemase; D008911:Minocycline; D003091:Colistin
keywords: Colistin-resistance; Enterobacteriaceae; Synergy; Treatment