- Design
- Multicentre retrospective observational cohort
- Population
- 1,147 adults discharged from 11 EDs with pyelonephritis on oral cephalosporins
- Primary outcome
- Composite treatment failure at 14 days
- Effect
- 19.6% (1st) vs 17.6% (2nd) vs 18.0% (3rd); 1st vs 3rd difference 1.6% (-3.4 to 6.5)
A retrospective cohort study across 11 US academic emergency departments included 1,147 adults discharged with pyelonephritis on an oral cephalosporin between 2023 and 2025; over 85% were women. Cephalexin made up most first-generation prescriptions, cefuroxime all second-generation and cefdinir most third-generation.
Treatment failure at 14 days, a composite of recurrent symptoms, a return visit, a new antibiotic or admission, was 19.6% with first-generation agents, 17.6% with second and 18.0% with third. Neither difference was significant (first vs third 1.6 points, 95% CI -3.4 to 6.5).
The result challenges the habit of reaching for a third-generation agent by default, but it is observational and from a US setting. Local resistance patterns, especially high rates of ESBL-producing E. coli in India, matter more than generation, and choosing an agent the urine culture supports is the priority.
- Send a urine culture before starting antibiotics in pyelonephritis.
- Choose an oral agent from local susceptibility data rather than defaulting to the newest generation.
- Arrange review of the culture result within 48 to 72 hours.
- About 1 in 5 discharged patients met the failure definition, so give clear return advice.
Why it matters
Third-generation cephalosporins are often prescribed by reflex, and this cohort found no advantage for them.
Don't overread it
Observational and from US hospitals; resistance patterns in India differ substantially.
The statistics, in plain English
The confidence interval for first versus second generation is wide (-7.1 to 11.1) because only 91 people received a second-generation agent, so a meaningful difference there cannot be ruled out. The first versus third comparison is more precise.
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