title: Epidemiology and outcome of infections with carbapenem-resistant Gram-negative bacteria treated with polymyxin B-based combination therapy.
abstract: BACKGROUND
  Infections with carbapenem-resistant Gram-negative bacteria (CRGNB) are increasing and are associated with a high mortality. Synergistic effects of combination therapy with a polymyxin, carbapenem, and rifampin have been observed in in vitro studies. Clinical data are limited to retrospective studies.
  
  
  METHODS
  We performed an observational cohort study of patients over 18 y of age who were treated with polymyxin B combination therapy.
  
  
  RESULTS
  One hundred and four patients were studied. The mean age was 77 y; 73% had recently received antibiotics, 67% had recently been hospitalized, and 47% lived in a nursing facility. The most common infections were pneumonia and urinary tract infection due to Acinetobacter baumannii (33%), Klebsiella pneumoniae (24%), and Pseudomonas aeruginosa (11%). Treatment regimens included polymyxin B with a carbapenem in 48%, with additional rifampin in 23%. Clinical success was achieved in 50% and reinfection occurred in 25%. Treatment-related acute renal failure occurred in 14.4%. No treatment-related hemodialysis was needed. All-cause hospital mortality was 47% and mortality after 6 months was 77%. No significant difference was found between treatment regimens. Age (odds ratio (OR) 10.4 per 10 y, p = 0.04), severity of acute illness (OR 2.2 per point, p < 0.001), and Charlson score (OR 1.12 per point, p = 0.04) were associated with hospital mortality. K. pneumoniae was associated with increased hospital survival compared to other CRGNB (p = 0.03).
  
  
  CONCLUSIONS
  CRGNB infections are associated with previous antibiotic and health care exposure. Mortality is related to age and the severity of chronic and acute illness.
authors.affiliation: From the 1 George Washington University Medical Center , Washington, DC , USA.
authors.forename: Robbert
authors.initials: R
authors.lastname: Crusio
authors.forename: Sriharsha
authors.initials: S
authors.lastname: Rao
authors.forename: Nisarg
authors.initials: N
authors.lastname: Changawala
authors.forename: Vishesh
authors.initials: V
authors.lastname: Paul
authors.forename: Ceres
authors.initials: C
authors.lastname: Tiu
authors.forename: Joost
authors.initials: J
authors.lastname: van Ginkel
authors.forename: Edward
authors.initials: E
authors.lastname: Chapnick
authors.forename: Yizhak
authors.initials: Y
authors.lastname: Kupfer
mesh_terms: D000367:Age Factors; D000368:Aged; D000369:Aged, 80 and over; D000900:Anti-Bacterial Agents / Q000009:adverse effects / Q000494:pharmacology* / Q000627:therapeutic use*; D015780:Carbapenems / Q000494:pharmacology / Q000627:therapeutic use*; D015331:Cohort Studies; D004359:Drug Therapy, Combination / Q000379:methods; D005260:Female; D006090:Gram-Negative Bacteria / Q000187:drug effects* / Q000302:isolation & purification; D016905:Gram-Negative Bacterial Infections / Q000188:drug therapy* / Q000382:microbiology / Q000473:pathology; D006801:Humans; D008297:Male; D008875:Middle Aged; D011112:Polymyxin B / Q000009:adverse effects / Q000627:therapeutic use*; D011446:Prospective Studies; D051437:Renal Insufficiency / Q000139:chemically induced / Q000453:epidemiology; D012293:Rifampin / Q000494:pharmacology / Q000627:therapeutic use; D016019:Survival Analysis; D016896:Treatment Outcome; D018440:beta-Lactam Resistance
chemical_list: D000900:Anti-Bacterial Agents; D015780:Carbapenems; D011112:Polymyxin B; D012293:Rifampin