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Updated: Aug 9, 2026

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses
11:17

Multiplex Therapeutic Drug Monitoring by Isotope-dilution HPLC-MS/MS of Antibiotics in Critical Illnesses

Published on: August 30, 2018

Association between tazobactam-piperacillin exposure and the subsequent emergence in gram-negative rods: Findings

Ezaki Masayoshi1, Kato Noriko2, Nagaoka Kentaro1

  • 1Department of Clinical Infectious Diseases, Toyama University Hospital, Toyama, Japan.

International Journal of Antimicrobial Agents
|August 7, 2026
PubMed
Abstract

Insights

Prolonged exposure to tazobactam-piperacillin (TZP) for 14 days or more increases the risk of developing resistant gram-negative rods (GNRs). Optimizing TZP duration is key to antimicrobial stewardship.

Area of Science:

  • Infectious Diseases
  • Clinical Microbiology
  • Antimicrobial Resistance

Background:

  • The relationship between tazobactam-piperacillin (TZP) exposure and the development of subsequent antimicrobial resistance is not well understood.
  • Gram-negative rods (GNRs) are a significant cause of hospital-acquired infections, and resistance to commonly used antibiotics like TZP is a growing concern.

Purpose of the Study:

  • To investigate the association between the duration of TZP treatment and the emergence of TZP-resistant GNRs.
  • To identify independent risk factors for the development of TZP resistance in GNRs.

Main Methods:

  • A retrospective observational study was conducted at a single institution.
  • Data from 1,619 patients treated with TZP between January 2021 and December 2023 were analyzed.
  • Multivariable Fine-Gray regression was used to identify risk factors for new TZP-resistant GNRs within 180 days of exposure.

Main Results:

  • 5.9% of patients developed new TZP-resistant GNRs within 180 days.
  • Patients receiving TZP for ≥14 days had a higher cumulative incidence of resistance (12.0%).
  • Prolonged TZP exposure (≥14 days) was an independent risk factor (aSHR 1.73; 95% CI 1.03-2.89).
  • Pseudomonas aeruginosa and AmpC-producing Enterobacterales were common resistant isolates.

Conclusions:

  • Extended TZP treatment duration (≥14 days) is an independent predictor of subsequent TZP-resistant GNR emergence.
  • Initial microbiological findings and specific clinical factors also contribute to resistance development.
  • Antimicrobial stewardship programs should focus on optimizing TZP treatment duration to combat resistance.
Keywords:
Antimicrobial resistanceAntimicrobial stewardshipEnterobacteralesExposure durationTazobactam/piperacillin

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