UMEM Educational Pearls

Background:

The 2010 Infectious Diseases Society of America (IDSA) cystitis and pyelonephritis guidelines recommend fluoroquinolones (FQs) as first line agents for pyelonephritis treatment and also support trimethoprim-sulfamethoxazole (TMP-SMX) usage if the urinary pathogen is known to be susceptible. However, alternative regimens need to be evaluated as FQs are increasingly associated with serious adverse events, and E coli resistance rates to both FQs and TMP-SMX are rising nationally. The Cephalosporins for Outpatient Pyelonephritis in the Emergency Department (COPY-ED) study aimed to evaluate the effectiveness of oral cephalosporins in acute pyelonephritis treatment when compared to IDSA guideline-endorsed first line treatments.

Study design:

This multicenter, retrospective observational cohort study screened patients with a primary diagnosis of uncomplicated or complicated pyelonephritis using ICD-10 codes. They included all patients >18 years of age who reported symptoms of a UTI and were discharged home on oral antimicrobial therapy. Exclusion criteria included pregnancy, acute or chronic prostatitis, orchitis, epididymitis, or urinary tract surgery within 7 days prior to ED visit or surgery planned during the study period.

The primary outcome was rate of outpatient treatment failure within 14 days of discharge from the emergency department with cephalosporins compared to FQs and TMP-SMX. 

Patient Population:

• 647 patients received cephalosporins and 204 received FQs or TMP/SMX. 
• Majority female (85.9% in the cephalosporin group, 83.3% in the FQ and TMP/SMX group)
• Majority with uncomplicated pyelonephritis (72% in the cephalosporin group vs. 73% of the FQ and TMP/SMX group)
• The median age was 36 in the cephalosporin group and 33 in the FQ/TMP/SMX group.
• 60.4% of the cephalosporin group and 46.6% of the FQ + TMP/SMX group received at least one dose of an IV antibiotic prior to discharge (most commonly ceftriaxone)

Results:

Rates of treatment failure at 14 days were not statistically significant between groups, with a rate of 17.2% in the cephalosporin group and a rate of 22.5% in the FQ + TMP/SMX group. After adjusting for gender, complicated infections, previous use of intravenous or oral antibiotics, and urinary tract abnormality, the odds of treatment failure at 14 days were still not significantly different in patients who received fluoroquinolone or TMP/SMX (adjusted OR 1.275 [95% CI 0.86 to 1.9]) compared to cephalosporins.

Secondary outcomes included rates of treatment failure with first generation cephalosporins (cephalexin, cefadroxil, cefuroxime) and third generation cephalosporins (cefpodoxime, cefuroxime), rates of appropriate therapy selected based on urine culture susceptibilities, and rates of treatment failure compared to duration of treatment prescribed. None of these outcomes found statistically significant differences between groups.

Study Limitations:

• Patients could receive care at locations outside of the study sites either before or after their ED visit, which may lead to a falsely low incidence of reported treatment failure.
• Cefazolin susceptibility was used as a surrogate for all oral cephalosporin susceptibility, which may lead to underreporting of true resistance to oral first generation cephalosporins and/or overreporting incidence of resistance to third generation cephalosporins.

Key Takeaways:

• Rates of treatment failure appear to be similar between cephalosporins and guideline-endorsed treatments in pyelonephritis - though it is important to note this study predominately included younger female patients with uncomplicated pyelonephritis 
• The 2010 IDSA guideline recommendations for pyelonephritis may be outdated given changes in E Coli resistance patterns as well as increased recognition of adverse events with FQ use.

References

1. Koehl, Jenny et al. “Cephalosporins for Outpatient Pyelonephritis in the Emergency Department: COPY-ED Study.” Annals of emergency medicine vol. 85,3 (2025): 240-248. doi:10.1016/j.annemergmed.2024.10.013
2. Gupta, Kalpana et al. “International clinical practice guidelines for the treatment of acute uncomplicated cystitis and pyelonephritis in women: A 2010 update by the Infectious Diseases Society of America and the European Society for Microbiology and Infectious Diseases.” Clinical infectious diseases: an official publication of the Infectious Diseases Society of America vol. 52,5 (2011): e103-20. doi:10.1093/cid/ciq257
3. Faine, Brett A et al. “High prevalence of fluoroquinolone-resistant UTI among US emergency department patients diagnosed with urinary tract infection, 2018-2020.” Academic emergency medicine: official journal of the Society for Academic Emergency Medicine vol. 29,9 (2022): 1096-1105. doi:10.1111/acem.14545