COPY That: Re-thinking Pyelonephritis Protocols in the Emergency Department

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Pyelonephritis is a commonly treated diagnosis in the emergency department. With resistance rates climbing to the first-line recommended fluoroquinolones and Bactrim, are other antibiotics appropriate in treating pyelonephritis? Join Dr Gabor as she discusses this article and its treatment recommendations for outpatient pyelonephritis with cephalosporins and how it compares to treatment with the more traditional fluoroquinolones / bactrim route.

THE PODCAST

Koehl J, Spolsdoff D, Negaard B, Lewis A, Santiago R, Krenz J, Polotti A, Feldman R, Slocum G, Zimmerman D, Howington GT, Sarangarm P, Mattson AE, Brown C, Zepeski A, Rech MA, Faine B. Cephalosporins for Outpatient Pyelonephritis in the Emergency Department: COPY-ED Study. Ann Emerg Med. 2025 Mar;85(3):240-248. doi: 10.1016/j.annemergmed.2024.10.013. Epub 2024 Nov 20. PMID: 39570254.

A SUMMARY

Background

  • UTIs account for more than 3 million ED visits annually and are associated with a significant cause of morbidity and hospitalizations.

  • Historically, fluoroquinolones and Bactrim have been first-line outpatient antibiotics, but with resistance rates climbing, cephalosporins are being used more often.

  • There is not much data on the performance of cephalosporins for treating outpatient pyelonephritis.

Study Design

  • This was a multicenter, retrospective observational cohort study that looked at the effectiveness of cephalosporins vs IDSA-recommended Fluoroquinolones/Bactrim in treating outpatient pyelonephritis.

  • The researchers pulled data from 11 U.S. emergency departments between January 2021 and October 2023.

  • Patients included were adults who were 18 years or older, who were diagnosed with pyelonephritis based on ICD-10 codes, and discharged home from the ED.

  • Pyelonephritis was defined as urinary symptoms plus “something else”, including fever, chills, flank pain, or CVA tenderness.

Population

  • There were 851 total patients included. 

  •  647 patients, or 76%, received oral cephalosporins (Keflex being the most common).

    • The average duration of treatment was 9 days.

    • Around 60% received an IV antibiotic dose before discharge.

  • The remaining 204 patients, or 24%, received fluoroquinolones or Bactrim.

  • The average treatment duration was around 7-9 days.

  • About 50% received a dose of IV antibiotics before discharge. 

Outcome

  • The primary outcome was treatment failure within 14 days. This was defined as any of the following:

    • Recurrence of symptoms

    • Repeat ED visits or hospital admission for similar symptoms

    • A new antibiotic prescription

  • They found no significant difference in treatment failure between the two groups

  • When analyzing various secondary outcomes, they found the following:

    • No significant difference between 1st or 2nd generation cephalosporins compared to third-generation or IDSA guideline therapy

    • No difference in appropriateness of empiric treatment based on urine cultures

    • Shorter antibiotic courses than what IDSA recommends did not lead to more failures

Limitations

  • One limitation of the study is the somewhat subjective definition of pyelonephritis used by the researchers. With some of the included patients being based off of documentation in the EMR of patient-described symptoms, it is possible that patients included in this study did not actually have pyelonephritis but were instead treated for a UTI and this resulted in appropriate coverage with cephalosporins.

  • Antibiotic selection was not randomized—it depended on clinician choice, so there could be selection bias.

  • Another limitation is that a definition of failure was repeat ED visits, but this was restricted to reviewing the EMR. If the patient had received care somewhere else that did not show up in the EMR, like an urgent care or different ED, it is possible this was not caught, and this patient was counted as having a successful treatment.

Sweeping Literature Review and other Guidelines

The IDSA recently published new guidelines in July 2025.

  • They re-classified UTIs into two categories: uncomplicated and complicated.

  • Acute pyelonephritis is no longer a separate category but instead lumped into “complicated UTIs”.

  • “Complicated UTI” no longer includes any male with a UTI.

  • IDSA does recommend shortening the duration of treatment for pyelonephritis if symptoms are improving, which is supported by the findings in this paper.

Final Recommendations

Overall, the IDSA guidelines currently still recommend fluoroquinolones or Bactrim as first-line, and cephalosporins as second-line. This study however suggests that cephalosporins may be a reasonable alternative. More prospective studies are needed moving forward, with stricter definitions of pyelonephritis which address some of the limitations discussed.

AUTHORSHIP

Written by: Victoria Gabor, MD, PGY-3 University of Cincinnati Department of Emergency Medicine

Editing, Posting, and Audio Editing by Anita Goel, MD Adjunct Associate Professor, University of Cincinnati Department of Emergency Medicine.

Cite as: Gabor, V., Goel, A. Copy That: Re-Thinking Pyelonephritis Protocols in the Emergency Department. TamingtheSRU.com. www.tamingthesru.com/blog/journal-club-cephalosporins-for-pyelonephritis. 10/4/2025.