Methods: We conducted a national retrospective cohort study of patients admitted to any VA hospital from 2003 through 2015. Inclusion criteria were: i) hospital admission; ii) age ≥ 18 years; and iii) ≥ 1 blood culture positive for a CRE pathogen. Patients treated with a polymyxin agent < 48 hours were excluded. The primary outcome was 28-day survival, evaluated by Cox regression.
Results: A total of 312 patients met study criteria (polymyxin monotherapy, n=96; polymyxin/carbapenem combination therapy, n=216). Combination carbapenem agents included imipenem (n=140), meropenem (n=56), doripenem (n=12), and ertapenem (n=8). Overall, 28-day mortality was 36.5% (n=114/312). Polymyxin/carbapenem combination therapy was significantly associated with improved 28-day survival compared to polymyxin monotherapy (hazard ratio [HR], 0.58; 95% confidence interval [CI], 0.39-0.85; P=0.005). With regard to individual carbapenem agents, both combination meropenem (HR, 0.38; 95% CI, 0.20-0.71; P=0.002) and imipenem (HR, 0.64; 95% CI, 0.42-0.96; P=0.034) were associated with significantly improved 28-day survival compared to polymyxin monotherapy. There were no significant differences in survival between combination therapies with other carbapenem agents versus polymyxin monotherapy.
Conclusion: Combination polymyxin/carbapenem therapy was associated with significantly improved 28-day survival compared to polymyxin monotherapy in the treatment of CRE-BSI. This survival benefit was most pronounced when combination meropenem or imipenem were used.
N. S. Britt,
Merck & Co., Inc.:
Gilead Sciences, Inc.: Grant Investigator , Consulting fee
Merck & Co., Inc.: Grant Investigator , Consulting fee
Theravance Biopharma US, Inc.: Board Member and Speaker's Bureau , Speaker honorarium
E. M. Potter, None
M. E. Steed, Merck & Co., Inc.: Grant Investigator , Research grant