title: Predictors of mortality in bloodstream infections caused by Klebsiella pneumoniae carbapenemase-producing K. pneumoniae: importance of combination therapy.
abstract: BACKGROUND
  The spread of Klebsiella pneumoniae (Kp) strains that produce K. pneumoniae carbapenemases (KPCs) has become a significant problem, and treatment of infections caused by these pathogens is a major challenge for clinicians.
  
  
  METHODS
  In this multicenter retrospective cohort study, conducted in 3 large Italian teaching hospitals, we examined 125 patients with bloodstream infections (BSIs) caused by KPC-producing Kp isolates (KPC-Kp) diagnosed between 1 January 2010 and 30 June 2011. The outcome measured was death within 30 days of the first positive blood culture. Survivor and nonsurvivor subgroups were compared to identify predictors of mortality.
  
  
  RESULTS
  The overall 30-day mortality rate was 41.6%. A significantly higher rate was observed among patients treated with monotherapy (54.3% vs 34.1% in those who received combined drug therapy; P = .02). In logistic regression analysis, 30-day mortality was independently associated with septic shock at BSI onset (odds ratio [OR]: 7.17; 95% confidence interval [CI]: 1.65-31.03; P = .008); inadequate initial antimicrobial therapy (OR: 4.17; 95% CI: 1.61-10.76; P = .003); and high APACHE III scores (OR: 1.04; 95% CI: 1.02-1.07; P < .001). Postantibiogram therapy with a combination of tigecycline, colistin, and meropenem was associated with lower mortality (OR: 0.11; 95% CI: .02-.69; P = .01).
  
  
  CONCLUSIONS
  KPC-Kp BSIs are associated with high mortality. To improve survival, combined treatment with 2 or more drugs with in vitro activity against the isolate, especially those also including a carbapenem, may be more effective than active monotherapy.
authors: Institute of Infectious Diseases, Catholic University of the Sacred Heart, A. Gemelli Hospital, Rome. tumbarello@rm.unicatt.it
authors: Mario
authors: M
authors: Tumbarello
authors: Pierluigi
authors: P
authors: Viale
authors: Claudio
authors: C
authors: Viscoli
authors: Enrico Maria
authors: EM
authors: Trecarichi
authors: Fabio
authors: F
authors: Tumietto
authors: Anna
authors: A
authors: Marchese
authors: Teresa
authors: T
authors: Spanu
authors: Simone
authors: S
authors: Ambretti
authors: Francesca
authors: F
authors: Ginocchio
authors: Francesco
authors: F
authors: Cristini
authors: Angela Raffaella
authors: AR
authors: Losito
authors: Sara
authors: S
authors: Tedeschi
authors: Roberto
authors: R
authors: Cauda
authors: Matteo
authors: M
authors: Bassetti
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000627:therapeutic use; D016470:Bacteremia / Q000175:diagnosis* / Q000382:microbiology / Q000401:mortality*; D001426:Bacterial Proteins / Q000378:metabolism*; D015331:Cohort Studies; D003661:Decision Support Techniques; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006801:Humans; D007558:Italy; D007710:Klebsiella Infections / Q000175:diagnosis* / Q000382:microbiology / Q000401:mortality*; D007711:Klebsiella pneumoniae / Q000201:enzymology* / Q000302:isolation & purification; D008297:Male; D008875:Middle Aged; D011379:Prognosis; D012189:Retrospective Studies; D012307:Risk Factors; D012720:Severity of Illness Index; D016019:Survival Analysis; D001618:beta-Lactamases / Q000378:metabolism*
chemical_list: D000900:Anti-Bacterial Agents; D001426:Bacterial Proteins; D001618:beta-Lactamases; C063912:carbapenemase