305 - Prevalence of Ceftriaxone Susceptible, Piperacillin-tazobactam Non-susceptible Escherichia coli Bacteremia in Patients with Hematologic Malignancy

Background: Piperacillin-tazobactam (TZP) is common empiric and targeted therapy for gram-negative bacteremia in patients with hematologic malignancy. Resistance to TZP tends to occur concurrently with ceftriaxone (CRO) resistance; however, the prevalence of TZP nonsusceptibility in CRO susceptible Escherichia coli (E. coli) in patients with hematologic malignancy is unknown. Therefore, we sought to determine the prevalence of TZP nonsusceptible, CRO susceptible E. coli bacteremia at a cancer center.

Methods: This is a retrospective cohort study of adult (age > 18) patients with E. coli bacteremia admitted to the Leukemia or Stem Cell Transplant (SCT) services at The University of Texas MD Anderson Cancer Center (MDACC) between 8/2016 and 7/2019. Isolates were categorized according to current CLSI resistance breakpoints. A first isolate was defined as the first positive blood culture and subsequent episodes of bacteremia were defined as any E. coli isolate obtained at least 24 hours after the first negative blood culture.

Results: The overall prevalence of TZP resistant CRO susceptible E. coli from 404 isolates was 7.7% and varied by service. There was a higher prevalence in the Leukemia service compared to SCT, 9.8% vs 2.5%, respectively (p < 0.01). 46% of isolates were CRO nonsusceptible, of which 91% were extended-spectrum beta-lactamase (ESBL) producers, identified by Vitek 2 or Accelerate Pheno. The TZP MIC₅₀ was 4ug/ml, MIC₉₀ was 128ug/ml, with an MIC range of 3ug/ml to ≥ 256ug/ml. The TZP MIC distribution varied based upon CRO phenotype. In CRO susceptible isolates the MIC₅₀ and MIC₉₀ were 4ug/ml and 64ug/ml, respectively, compared to 8ug/ml and 128ug/ml in CRO nonsusceptible isolates (p < 0.01). TZP resistance was more common in CRO nonsusceptible isolates (31.6% vs 12.0%, p < 0.01) and was more frequent with subsequent episodes of bacteremia compared to the first (39.5% vs 20.1%, p < 0.01).

Conclusion: In patients with hematologic malignancy and E. coli bacteremia, TZP resistance is common with significant variations by CRO phenotype. TZP resistance becomes more common with subsequent episodes of bacteremia compared to the first. The clinical implications and genetic cause of this phenotype is currently unknown and warrants further investigation.