The role of tazobactam-based combinations for the management of infections due to extended-spectrum β-lactamase-producing Enterobacterales: Insights from the Society of Infectious Diseases Pharmacists

Marguerite L. Monogue, Emily L. Heil, Samuel L. Aitken, Jason M. Pogue

Research output: Contribution to journalComment/debatepeer-review

Abstract

Extended-spectrum β-lactamase (ESBL)-producing Enterobacterales are a global threat to public health due to their antimicrobial resistance profile and, consequently, their limited available treatment options. Tazobactam is a sulfone β-lactamase inhibitor with in vitro inhibitory activity against common ESBLs in Enterobacterales, including CTX-M. However, the role of tazobactam-based combinations in treating infections caused by ESBL-producing Enterobacterales remains unclear. In the United States, two tazobactam-based combinations are available, piperacillin-tazobactam and ceftolozane-tazobactam. We evaluated and compared the roles of tazobactam-based combinations against ESBL-producing organisms with emphasis on pharmacokinetic/pharmacodynamic exposures in relation to MIC distributions and established breakpoints, clinical outcomes data specific to infection site, and considerations for downstream effects with these agents regarding antimicrobial resistance development. While limited data with ceftolozane-tazobactam are encouraging for its potential role in infections due to ESBL-producing Enterobacterales, further evidence is needed to determine its place in therapy. Conversely, currently available microbiologic, pharmacokinetic, pharmacodynamic, and clinical data do not suggest a role for piperacillin-tazobactam, and we caution clinicians against its usage for these infections.

Original languageEnglish (US)
Pages (from-to)864-880
Number of pages17
JournalPharmacotherapy
Volume41
Issue number10
DOIs
StatePublished - Oct 2021

Keywords

  • ceftolozane
  • Enterobacterales
  • extended-spectrum β-lactamases
  • microbiome
  • pharmacodynamics
  • pharmacokinetics
  • piperacillin
  • tazobactam

ASJC Scopus subject areas

  • Pharmacology (medical)

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