TOPLINE

Patients with piperacillin-tazobactam (TZP)-resistant monomicrobial Escherichia coli or Klebsiella pneumoniae bloodstream infections (BSIs) did not have significantly higher 30-day mortality than those with TZP-susceptible BSIs after adjustment for baseline risk factors, according to a Danish cohort study.

METHODOLOGY

• Researchers conducted a cohort study using data from Danish national health registers and microbiology databases from November 2018 to November 2024 to compare mortality risk between patients with TZP-resistant and TZP-susceptible BSIs.
• They analyzed 34,379 patients aged ≥ 18 years (median age, 76 years; 51.5% men) with a blood culture positive for E coli (n = 28,649) or K pneumoniae (n = 6314); only the first (index) BSI for each patient and pathogen was included.
• Researchers compared 30-day mortality rates and mortality risk between TZP-resistant and TZP-susceptible BSIs using multivariable analysis adjusted for sex, age, comorbidity, year, length of hospital stay before BSI, prior inpatient stays, and prior BSI with a different pathogen species.
• Subgroup analyses evaluated whether the association between TZP resistance and mortality differed by empirical treatment, infection source, and calendar year.

TAKEAWAY

• Among patients with E coli BSI, crude 30-day mortality was higher for TZP-resistant vs TZP-susceptible infections (15.8% vs 13.1%; hazard ratio [HR], 1.22; 95% CI, 1.08-1.38), but after multivariable adjustment, the difference was not significant (adjusted HR [aHR], 1.00; 95% CI, 0.89-1.14).
• Similarly, among patients with K pneumoniae BSI, crude mortality was higher with TZP-resistant vs TZP-susceptible infections (21.1% vs 16.9%; HR, 1.27; 95% CI, 1.05-1.52), but this association was nullified after adjustment for baseline risk factors (aHR, 1.07; 95% CI, 0.89-1.29).
• Adjustment for demographic factors alone (sex, age group, and calendar year) did not remove the association between TZP resistance and mortality (E coli: aHR, 1.26; 95% CI, 1.11-1.43; K pneumoniae: aHR, 1.34; 95% CI, 1.11-1.61). However, adjustment for clinical factors nullified the association (E coli: aHR, 0.99; 95% CI, 0.87-1.12; K pneumoniae: aHR, 1.09; 95% CI, 0.90-1.33).
• Subgroup analyses found no significant differences in the association between TZP resistance and mortality risk based on empirical treatment, hospital-associated vs community-acquired BSI status, or calendar year.

IN PRACTICE

“In this cohort study of Danish patients with a monomicrobial E coli or K pneumoniae BSI, patients with a TZP-resistant BSI did not have a higher mortality risk than patients with a TZP-susceptible E coli or K pneumoniae BSI. This is important given concerns about the increasing use of TZP as a preferred empirical treatment for BSIs and the concurrent rise in resistance in Denmark between 2018 and 2024,” the authors of the study concluded. 

SOURCE

The study was led by Erich Tusch, PhD, Department of Data Science and AI in Health, Statens Serum Institut, Copenhagen, Denmark. It was published online on July 22, 2026, in JAMA Network Open.

LIMITATIONS

The study assessed mortality risk based on baseline resistance status rather than treatment effectiveness and did not adjust for post-baseline treatment changes. Empirical treatment classification was limited by incomplete dose information, and data on infection source and severity were unavailable. The study results may not be applicable to settings with high carbapenem resistance because carbapenem resistance was low in Denmark.

DISCLOSURES

The study received support from the Independent Research Fund Denmark. Tusch disclosed receiving grants from Statens Serum Institut during the conduct of the study. Some authors reported receiving grants or personal fees from various sources, including the Independent Research Fund Denmark. Full disclosures are available in the original article.

This article was created using several editorial tools, including AI, as part of the process. Human editors reviewed this content before publication.