TOPLINE

A multicenter study found no significant differences in 14-day treatment failure rates among patients with acute pyelonephritis discharged from emergency departments (EDs) on first-, second-, or third-generation oral cephalosporins, suggesting no clear treatment advantage for later-generation agents.

METHODOLOGY

• Researchers retrospectively analyzed records of adults discharged from 11 academic EDs across the US between 2023 and 2025. 
• The analysis included 1147 adults with acute pyelonephritis who were discharged on an oral cephalosporin: 618 received first-generation, 91 received second-generation, and 438 received third-generation cephalosporins.
• Researchers assessed 14-day treatment failure rates among the patients receiving first-, second-, or third-generation cephalosporins; treatment failure was defined as the recurrence of urinary symptoms, a repeat ED or urgent care visit for a urinary tract infection (UTI), a new antibiotic prescription for urinary symptoms, or hospitalization for a UTI.
• They also assessed modifications to antibiotic regimens based on urine culture and susceptibility results.

TAKEAWAY

• No significant differences were observed in 14-day treatment failure rates across cephalosporin-generation cohorts (first vs second generation, 19.6% vs 17.6%; first vs third generation, 19.6% vs 18.0%).
• Empirical treatment showed greater activity against cefazolin-susceptible isolates in the second-generation cohort (91.5%) than in the first-generation (76.5%) and third-generation (80.6%) cohorts.
• Treatment failure occurred in 71.1% of the patients with cefazolin-resistant isolates vs 17.5% of those with cefazolin-susceptible isolates. In the resistant group, 86% of the failures stemmed from culture-reported resistance, whereas in the susceptible group, 28% of the failures involved clinical worsening.
• Having at least one antimicrobial resistance risk factor was associated with higher odds of treatment failure (adjusted odds ratio [aOR], 1.91; 95% CI, 1.37-2.64), as was older age (aOR, 1.01; 95% CI, 1.01-1.02).

IN PRACTICE

"These findings support an individualized approach to antimicrobial treatment selection, incorporating resistance patterns, patient-specific factors, and adverse event profiles to guide optimal therapy decisions," the authors wrote.

SOURCE

The study was led by Alicia E. Mattson, PharmD, Mayo Clinic, Rochester, Minnesota. It was published online on October 6, 2026, in Annals of Emergency Medicine.

LIMITATIONS

The retrospective design of the study limited the verification of medication adherence and follow-up outside the health system. The diagnosis relied on International Classification of Diseases codes and a combination of laboratory and clinical criteria, potentially resulting in misclassification. The smaller sample size of the second-generation cephalosporin cohort may have reduced statistical power, and the influence of unmeasured confounding factors could not be excluded.

DISCLOSURES

The REDCap database was funded by the National Center for Advancing Translational Sciences of the National Institutes of Health. The authors reported having no conflicts of interest.

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