Factors Associated with Mortality in Carbapenem-Resistant Enterobacteriaceae Bacteremia: Focus on Antibiotic Therapy

BACKGROUND: Infections caused by carbapenem resistant Enterobacteriaceae (CRE) are associated with high mortality. Optimal treatment for CRE bacteremia remains unclear, including the role of combination therapy, carbapenem-containing regimens, or newer antimicrobials, such as ceftazidime-avibactam (CAZ-AVI). The objective of this study was to evaluate risk factors associated with mortality in patients with CRE bacteremia, with a focus on antimicrobial therapy. METHODS: This was a multicenter, retrospective cohort study of inpatients within Carolinas HealthCare System who had a positive blood culture with CRE (Klebsiella spp., Enterobacter spp., or Escherichia coli) between January 1, 2010 and September 30, 2016. CRE isolates were identified as pathogens with an ertapenem MIC ≥ 1 mcg/mL. The primary endpoint was death within 28 days after the first positive blood culture in patients with CRE bacteremia. Clinical variables, including the use of specific antimicrobials and combination therapy, were compared between 28-day survivors vs. non-survivors. RESULTS: A total of 73 patients were included with CRE bacteremia. The most common sources of infection identified were urine (42.5%) and intra-abdominal (38.4%). The overall 28-day mortality was 26%. Fifty-three (72.6%) patients received combination antibiotic therapy and 20 (27.4%) received monotherapy. Combination therapy with in vitro active agents (36.8% vs. 33.3%, P = 0.87) and the use of carbapenem-containing regimens (47.4% vs. 46.3%, P = 0.74) did not differ between those who died and survived, respectively. One patient treated with CAZ-AVI as monotherapy died, but only eight patients received this antibiotic. There was a trend towards higher use of tigecycline in the group that died compared with the group that survived (73.7% vs. 59.3%, P = 0.26). CONCLUSION: There did not appear to be a difference in mortality at 28 days with the use of combination therapy or a carbapenem-containing regimen. While a statistically significant difference was not demonstrated, tigecycline-containing regimens may be associated with increased mortality in the treatment of CRE bacteremia. Larger prospective studies are necessary to further elucidate the role of combination therapy and newer agents, such as CAZ-AVI, in this patient population. DISCLOSURES: C. Polk, The Medicines Company: Investigator, Research support.