title: Colistin and rifampicin compared with colistin alone for the treatment of serious infections due to extensively drug-resistant Acinetobacter baumannii: a multicenter, randomized clinical trial.
abstract: BACKGROUND
  Extensively drug-resistant (XDR) Acinetobacter baumannii may cause serious infections in critically ill patients. Colistin often remains the only therapeutic option. Addition of rifampicin to colistin may be synergistic in vitro. In this study, we assessed whether the combination of colistin and rifampicin reduced the mortality of XDR A. baumannii infections compared to colistin alone.
  
  
  METHODS
  This multicenter, parallel, randomized, open-label clinical trial enrolled 210 patients with life-threatening infections due to XDR A. baumannii from intensive care units of 5 tertiary care hospitals. Patients were randomly allocated (1:1) to either colistin alone, 2 MU every 8 hours intravenously, or colistin (as above), plus rifampicin 600 mg every 12 hours intravenously. The primary end point was overall 30-day mortality. Secondary end points were infection-related death, microbiologic eradication, and hospitalization length.
  
  
  RESULTS
  Death within 30 days from randomization occurred in 90 (43%) subjects, without difference between treatment arms (P = .95). This was confirmed by multivariable analysis (odds ratio, 0.88 [95% confidence interval, .46-1.69], P = .71). A significant increase of microbiologic eradication rate was observed in the colistin plus rifampicin arm (P = .034). No difference was observed for infection-related death and length of hospitalization.
  
  
  CONCLUSIONS
  In serious XDR A. baumannii infections, 30-day mortality is not reduced by addition of rifampicin to colistin. These results indicate that, at present, rifampicin should not be routinely combined with colistin in clinical practice. The increased rate of A. baumannii eradication with combination treatment could still imply a clinical benefit.
  
  
  BACKGROUND
  NCT01577862.
authors.affiliation: Internal Medicine Section, Department of Cardiothoracic Sciences, University of Naples S.U.N. and AORN Ospedali dei Colli, Monaldi Hospital, Italy.
authors.forename: Emanuele
authors.initials: E
authors.lastname: Durante-Mangoni
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Signoriello
authors.forename: Roberto
authors.initials: R
authors.lastname: Andini
authors.forename: Annunziata
authors.initials: A
authors.lastname: Mattei
authors.forename: Maria
authors.initials: M
authors.lastname: De Cristoforo
authors.forename: Patrizia
authors.initials: P
authors.lastname: Murino
authors.forename: Matteo
authors.initials: M
authors.lastname: Bassetti
authors.forename: Paolo
authors.initials: P
authors.lastname: Malacarne
authors.forename: Nicola
authors.initials: N
authors.lastname: Petrosillo
authors.forename: Nicola
authors.initials: N
authors.lastname: Galdieri
authors.forename: Paola
authors.initials: P
authors.lastname: Mocavero
authors.forename: Antonio
authors.initials: A
authors.lastname: Corcione
authors.forename: Claudio
authors.initials: C
authors.lastname: Viscoli
authors.forename: Raffaele
authors.initials: R
authors.lastname: Zarrilli
authors.forename: Ciro
authors.initials: C
authors.lastname: Gallo
authors.forename: Riccardo
authors.initials: R
authors.lastname: Utili
mesh_terms: D000151:Acinetobacter Infections / Q000188:drug therapy* / Q000401:mortality; D040981:Acinetobacter baumannii / Q000187:drug effects* / Q000302:isolation & purification; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use*; D003091:Colistin / Q000627:therapeutic use*; D016638:Critical Illness; D024901:Drug Resistance, Multiple, Bacterial; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007362:Intensive Care Units; D007902:Length of Stay; D008297:Male; D008875:Middle Aged; D012293:Rifampin / Q000627:therapeutic use*; D016019:Survival Analysis; D062606:Tertiary Care Centers; D016896:Treatment Outcome
chemical_list: D000900:Anti-Bacterial Agents; D012293:Rifampin; D003091:Colistin
keywords: antimicrobial therapy; mortality; treatment efficacy; treatment safety; ventilator-associated pneumonia