title: Polymyxin B in Combination with Antimicrobials Lacking In Vitro Activity versus Polymyxin B in Monotherapy in Critically Ill Patients with Acinetobacter baumannii or Pseudomonas aeruginosa Infections.
abstract: There is no clinical evidence supporting the use of polymyxin B in combination with another antimicrobial for infections caused by extensively drug-resistant Acinetobacter baumannii or Pseudomonas aeruginosa isolates. We developed a cohort study of patients in two intensive care units from teaching hospitals to evaluate treatment with intravenous polymyxin B for ≥48 h for severe A. baumannii or P. aeruginosa infections. Covariates potentially associated with 30-day mortality were evaluated in a Cox proportional hazards model. A total of 101 patients were included; 33 (32.7%) were treated with polymyxin B in combination with an antimicrobial lacking in vitro activity and 68 (67.3%) with polymyxin B in monotherapy. The overall 30-day mortality was 59.4% (60 patients), comprising 42.4% (14 of 33) and 67.6% (46 of 68) in combination and monotherapy groups, respectively (P = 0.03). The mortality rates were 18.5/1,000 patient days and 36.4/1,000 patient days in the combination and monotherapy groups, respectively (P = 0.02). Combination therapy was independently associated with lower 30-day mortality (hazard ratio, 0.33; 95% confidence interval, 0.17 to 0.64; P = 0.001). Creatinine clearance of ≥60 ml/min was also a protective factor, while a higher acute physiology and chronic health evaluation (APACHE II) score and polymicrobial infection were associated with increased mortality. The results did not change after adding a propensity score for prescribing combination therapy into the model. The protective effect remained when only combination with β-lactam or carbapenem was considered and in both subgroups of patients: those with A. baumannii infection and those with lower respiratory tract infections. To our knowledge, this is the first clinical study to show a benefit of combination over monotherapy with polymyxin B for severe extensively drug-resistant A. baumannii or P. aeruginosa infections.
authors.affiliation: Infectious Diseases Service, Hospital São Lucas da Pontifícia Universidade Católica do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Maria Helena
authors.initials: MH
authors.lastname: Rigatto
authors.affiliation: School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Fabiane J
authors.initials: FJ
authors.lastname: Vieira
authors.affiliation: School of Pharmaceutical Sciences, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Laura C
authors.initials: LC
authors.lastname: Antochevis
authors.affiliation: Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil.
authors.forename: Tainá F
authors.initials: TF
authors.lastname: Behle
authors.affiliation: Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil.
authors.forename: Natane T
authors.initials: NT
authors.lastname: Lopes
authors.affiliation: Infectious Diseases Service, Hospital de Clínicas de Porto Alegre, Porto Alegre, Brazil Department of Internal Medicine, Medical School, Universidade Federal do Rio Grande do Sul, Porto Alegre, Brazil azavascki@hcpa.edu.br.
authors.forename: Alexandre P
authors.initials: AP
authors.lastname: Zavascki
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy; D040981:Acinetobacter baumannii / Q000187:drug effects*; D000368:Aged; D000369:Aged, 80 and over; D000890:Anti-Infective Agents / Q000494:pharmacology* / Q000627:therapeutic use*; D016638:Critical Illness; D004338:Drug Combinations; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D011112:Polymyxin B / Q000494:pharmacology* / Q000627:therapeutic use*; D011552:Pseudomonas Infections / Q000188:drug therapy; D011550:Pseudomonas aeruginosa / Q000187:drug effects*; D012189:Retrospective Studies
chemical_list: D000890:Anti-Infective Agents; D004338:Drug Combinations; D011112:Polymyxin B