1949. Polymyxin Monotherapy versus Combination Therapy for the Treatment of Carbapenem-Resistant Enterobacteriaceae Bloodstream Infection: A National Cohort Study
Session: Poster Abstract Session: Clinical: Bacteremia and Endocarditis
Saturday, October 7, 2017
Room: Poster Hall CD
Background: Carbapenem-resistant Enterobacteriaceae (CRE) represent an emerging and urgent public health threat. CRE bloodstream infections (CRE-BSI) are associated with high mortality yet optimal treatment remains unclear. Previous studies comparing polymyxin monotherapy versus combination therapy have largely been limited to single-center or small multicenter analyses. The objective of this study was to compare clinical outcomes between polymyxin monotherapy versus combination therapy with various carbapenem agents for CRE-BSI in a national cohort of hospitalized Veterans Affairs (VA) patients.

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.

Nicholas S. Britt, PharmD, MS, Research Department, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, KS, Nimish Patel, PharmD, PhD, Albany College of Pharmacy & Health Sciences, Albany, NY, Emily M. Potter, PharmD, Dwight D. Eisenhower Veterans Affairs Medical Center, Leavenworth, KS and Molly E. Steed, PharmD, University of Kansas School of Pharmacy, Lawrence, KS

Disclosures:

N. S. Britt, Merck & Co., Inc.: Grant Investigator , Consulting fee
Gilead Sciences, Inc.: Grant Investigator , Consulting fee

N. Patel, Gilead Sciences, Inc.: Grant Investigator , Research grant
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

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