2290. Carbapenem vs. Piperacillin–tazobactam Definitive Therapy for Patients with Bloodstream Infections Due to Ceftriaxone Not Susceptible Escherichia coli or Klebsiella species

Abstract Background Definitive therapy with piperacillin–tazobactam (TZP) for ceftriaxone (CRO)-resistant E. coli or K. pneumoniae bloodstream infections (BSI) has been shown to be inferior to carbapenem therapy in a randomized trial. Methods The Premier US database was queried for hospitalized patients with monomicrobial E. coli or Klebsiella spp BSI that were not susceptible (NS) to CRO between June 2015 and May 2018. Adults with index positive blood culture(s) drawn within the first 2 hospital days who were treated with active antibiotic therapy that continued for ≥3 consecutive days were included. We defined antibiotics administered on or prior to Day 3 as empirical therapy and all subsequent days as definitive therapy. Outcomes among patients who received definitive therapy with a carbapenem vs. TZP were evaluated. Results There were 954 patients (mean age, 67.6 years; 52.4% women) who met selection criteria and received active empirical therapy. 729/954 received carbapenem definitive therapy and 38/954 received TZP definitive therapy. Median Charlson Comorbidity Index scores were similar between carbapenem and TZP definitive therapy groups (6 vs. 5, P = 0.78). Crude 14-day in-hospital mortality for CRO-NS BSI due to E. coli or Klebsiella spp. was 4.4%. Definitive therapy with TZP (6/38; 15.8%) was associated with an increased likelihood of 14-day mortality relative to that of a carbapenem (22/729; 3.0%; P < 0.0001). The increased 14-day mortality observation was consistent in a multivariate cox proportional hazards model (adjusted hazard ratio, 5.70; 95% CI, 2.09 to 13.23; P = 0.002). Of patients who received carbapenem definitive therapy, 14-day mortality was 2.7% (19/693) if a carbapenem was part of empirical therapy and 8.3% (3/36; P = 0.06) if empirical therapy did not include a carbapenem. Median post-blood culture length of stay (7 vs. 6 days, P = 0.65) and hospital costs ($13,886 vs. $13,559, P = 0.62) were similar between carbapenem and TZP definitive therapy groups<./p> Conclusion In this large US database, definitive therapy with TZP was associated with an increased likelihood of 14-day mortality relative to that of definitive carbapenem therapy in patients with CRO-NS BSI due to E. coli or Klebsiella spp. These findings support recent clinical evidence in favor of definitive carbapenem therapy for CRO-NS BSI due to E. coli or Klebsiella spp. Disclosures All authors: No reported disclosures.