title: Treatment of KPC-producing Enterobacteriaceae: suboptimal efficacy of polymyxins.
abstract: Treatment of Klebsiella pneumoniae carbapenemase-producing Enterobacteriaceae infections (KPC-EI) remains a challenge. Combined therapy has been proposed as the best choice, but there are no clear data showing which combination therapy is superior. Our aim was to evaluate the effectiveness of antimicrobial regimens for treating KPC-EI. This was a retrospective cohort study of KPC-EI nosocomial infections (based on CDC criteria) between October 2009 and June 2013 at three tertiary Brazilian hospitals. The primary outcomes were the 30-day mortality for all infections and the 30-day mortality for patients with bacteraemia. Risk factors for mortality were evaluated by comparing clinical variables of survivors and nonsurvivors. In this study, 118 patients were included, of whom 78 had bacteraemia. Catheter-related bloodstream infections were the most frequent (43%), followed by urinary tract infections (n = 27, 23%). Monotherapy was used in 57 patients and combined treatment in 61 patients. The most common therapeutic combination was polymyxin plus carbapenem 20 (33%). Multivariate analysis for all infections (n = 118) and for bacteremic infections (n = 78) revealed that renal failure at the end of treatment, use of polymyxin and older age were prognostic factors for mortality. In conclusion, polymyxins showed suboptimal efficacy and combination therapy was not superior to monotherapy.
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil. Electronic address: maura.oliveira@hc.fm.usp.br.
authors.forename: M S
authors.initials: MS
authors.lastname: de Oliveira
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: D B
authors.initials: DB
authors.lastname: de Assis
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Infection Control Service, Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: M P
authors.initials: MP
authors.lastname: Freire
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: G V
authors.initials: GV
authors.lastname: Boas do Prado
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Machado
authors.affiliation: Infection Control Service, Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: E
authors.initials: E
authors.lastname: Abdala
authors.affiliation: Infection Control Service, Instituto do Câncer do Estado de São Paulo da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: L C
authors.initials: LC
authors.lastname: Pierrotti
authors.affiliation: Infection Control Service, Hospital Municipal Jose de Carvalho Florence, São José dos Campos, São Paulo, Brazil.
authors.forename: C
authors.initials: C
authors.lastname: Mangini
authors.affiliation: Infection Control Service, Hospital Municipal Jose de Carvalho Florence, São José dos Campos, São Paulo, Brazil.
authors.forename: L
authors.initials: L
authors.lastname: Campos
authors.affiliation: Laboratório de Investigação Médica LIM 03, Divisão de Laboratório Central, Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
authors.forename: H H
authors.initials: HH
authors.lastname: Caiaffa Filho
authors.affiliation: Department of Infection Control of Hospital das Clínicas da Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil; Department of Infectious Diseases, Laboratório de Investigação Médica - LIM 54 and Instituto de Medicina Tropical, University of São Paulo, Brazil.
authors.forename: A S
authors.initials: AS
authors.lastname: Levin
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D016470:Bacteremia / Q000188:drug therapy / Q000382:microbiology / Q000401:mortality; D001938:Brazil; D002648:Child; D002675:Child, Preschool; D015331:Cohort Studies; D004755:Enterobacteriaceae / Q000201:enzymology* / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000188:drug therapy* / Q000382:microbiology* / Q000401:mortality; D005260:Female; D006801:Humans; D007223:Infant; D008297:Male; D008875:Middle Aged; D011113:Polymyxins / Q000627:therapeutic use*; D012189:Retrospective Studies; D016019:Survival Analysis; D062606:Tertiary Care Centers; D016896:Treatment Outcome; D055815:Young Adult; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D011113:Polymyxins; D001618:beta-Lactamases
keywords: Carbapenem resistance; KPC; mortality; treatment