Urinary tract infections (UTIs) account for over 3 million emergency department (ED) visits annually and remain one of the most common indications for antibiotics. The 2010 Infectious Diseases Society of America (IDSA) guidelines recommend fluoroquinolones (FQs) as first-line therapy for acute uncomplicated pyelonephritis (AUP) if the prevalence of Escherichia coli resistance is <10%. However, since the guideline’s publication, E. coli FQ-resistance rates now exceed 20% in many US locations. Additionally, FQs are increasingly associated with serious AEs (SAEs) as well as collateral damage through the promotion of bacterial resistance. The U.S. FDA added “Boxed Warnings” describing risks of peripheral neuropathy and central nervous system effects while strengthening previous warnings regarding tendinopathy and hypoglycemia. Trimethoprim-sulfamethoxazole (TMP-SMX) has been used for decades for the treatment of AUP, however, E. coli resistance rates have exceeded 20% in most US communities for many years and IDSA guidelines recommend against its use. Due to the increasing prevalence of FQ and TMP-SMX resistance, which now exceed thresholds recommended for abandoning empiric administration of an antibiotic class, IDSA guidelines stress the need to evaluate alternative regimens.
A critical evidence gap, as highlighted by the IDSA guidelines is to understand the effectiveness of oral cephalosporins for the treatment of pyelonephritis in patients discharged from the ED. The impact of this project will be twofold. First, evidence supporting the use of cephalosporins for pyelonephritis is limited. Our proposed multi-center study comparing cephalosporins to guideline-endorsed antimicrobial treatment will fill the identified evidence gap from the IDSA guidelines and is the necessary step before proposing a randomized controlled trial. Second, we will be able to describe the prevalence of oral cephalosporins being utilized as the primary treatment for outpatient pyelonephritis in EDs across the U.S.
The outcomes of the proposed study are:
- The primary outcome is to determine the rate of treatment failure of cephalosporins compared to FQs and TMP-SMX in adult ED patients ≥18 years of age with uncomplicated/complicated pyelonephritis.
- Secondary outcomes include
- Necessity to change antimicrobial treatment based on culture and susceptibilities
- Days of antibiotic coverage,
- Return ED visit for UTI within 14 days of discharge, and
- Hospital admission with UTI as the primary diagnosis within 14 days of discharge.