- Design
- Multicentre retrospective cohort
- Population
- 1,147 adults discharged from 11 US EDs with pyelonephritis on an oral cephalosporin
- Primary outcome
- Treatment failure at 14 days
- Effect
- 19.6% vs 17.6% vs 18.0% (first vs second vs third generation)
This retrospective cohort at 11 US academic emergency departments included 1,147 adults, over 85% women, discharged with pyelonephritis on an oral cephalosporin between 2023 and 2025. Most received cephalexin, cefuroxime or cefdinir.
Treatment failure at 14 days — recurrent symptoms, a return visit, a new antibiotic or admission — was 19.6% with first-generation, 17.6% with second-generation and 18.0% with third-generation agents. The differences were small and not significant.
Oral cephalosporins are often considered second-line for pyelonephritis because of concerns about urinary concentrations. This suggests generation matters less than expected, though one in five patients still needed further care.
It is observational, and dosing, local resistance and culture results were not standardised. In India, where resistance to oral cephalosporins in E. coli is common, local antibiograms should drive choice.
- Base oral pyelonephritis treatment on local resistance patterns and the urine culture.
- Send a urine culture before starting antibiotics in every patient discharged with pyelonephritis.
- Arrange a check of culture results within 48–72 hours and switch if the organism is resistant.
- Warn patients that about one in five need further care, and give clear return advice.
Why it matters
It challenges the assumption that only later-generation cephalosporins work for upper urinary infection.
Don't overread it
This was observational and from the US; it does not override local resistance data.
The statistics, in plain English
The difference between first and third generation was 1.6 points with a confidence interval of −3.4 to 6.5, which includes no difference and modest differences either way. The second-generation group was small (91 patients), so that comparison is less precise.
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