Clinical outcomes in patients with piperacillin/ tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection

Ahmad Mourad; Alison G Smith; Jesse D Troy; Thomas L Holland; Rebekah H Wrenn; Nicholas A Turner

doi:10.1093/jac/dkae134

Clinical outcomes in patients with piperacillin/ tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection

J Antimicrob Chemother. 2024 May 6:dkae134. doi: 10.1093/jac/dkae134. Online ahead of print.

Authors

Ahmad Mourad¹, Alison G Smith², Jesse D Troy³, Thomas L Holland¹, Rebekah H Wrenn⁴, Nicholas A Turner¹

Affiliations

¹ Division of Infectious Diseases, Department of Medicine, Duke University Medical Center, Durham 27710, NC, USA.
² Department of Medicine, Duke University Medical Center, Durham, NC, USA.
³ Division of Biostatistics, Department of Biostatics & Bioinformatics, Duke University, Durham, NC, USA.
⁴ Department of Pharmacy, Duke University Medical Center, Durham, NC, USA.

PMID: 38708907
DOI: 10.1093/jac/dkae134

Abstract

Background: A small proportion of Escherichia coli and Klebsiella pneumoniae demonstrate in vitro non-susceptibility to piperacillin/tazobactam but retain susceptibility to ceftriaxone. Uncertainty remains regarding how best to treat these isolates.

Objectives: We sought to compare clinical outcomes between patients with piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae bloodstream infection receiving definitive therapy with ceftriaxone versus an alternative effective antibiotic.

Methods: We retrospectively identified patients with a positive blood culture for piperacillin/tazobactam-non-susceptible but ceftriaxone-susceptible E. coli or K. pneumoniae between 1 January 2013 and 31 December 2022. Patients were divided into one of two definitive treatment groups: ceftriaxone or alternative effective antibiotic. Our primary outcome was a composite of 90 day all-cause mortality, hospital readmission, or recurrence of infection. We used Cox proportional hazards models to compare time with the composite outcome between groups.

Results: Sixty-two patients were included in our analysis. Overall, median age was 63 years (IQR 49.5-71.0), the most common source of infection was intra-abdominal (25/62; 40.3%) and the median total duration of therapy was 12.0 days (IQR 9.0-16.8). A total of 9/22 (40.9%) patients in the ceftriaxone treatment group and 18/40 (45.0%) patients in the alternative effective antibiotic group met the composite endpoint. In an adjusted time-to-event analysis, there was no difference in the composite endpoint between groups (HR 0.67, 95% CI 0.30-1.50). The adjusted Bayesian posterior probability that the HR was less than or equal to 1 (i.e. ceftriaxone is as good or better than alternative therapy) was 85%.

Conclusions: These findings suggest that ceftriaxone can be used to effectively treat bloodstream infections with E. coli or K. pneumoniae that are non-susceptible to piperacillin/tazobactam but susceptible to ceftriaxone.

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