1433. Impact of 2019 US Food and Drug Administration (FDA) Guidance on Developing Drugs for Urinary Tract Infection (UTI) on the Perceived Efficacy of Antibiotics for the Treatment of Uncomplicated UTI (uUTI)

Abstract Background In 2019, the FDA issued guidance on drug development for treatment of UTIs. To explore the impact of this guidance, we compared clinical and microbiological outcomes of the fluoroquinolones norfloxacin and ciprofloxacin and the β-lactams pivmecillinam and sulopenem for treatment of uUTIs from original publications versus recent analyses conducted in accordance with the FDA guidance. Methods The efficacy of pivmecillinam 400 mg twice daily (BID), 3 days (3d) versus norfloxacin 400 mg BID, 3d was reported in a 2002 publication. Patient-level data were used to re-analyze clinical and microbiological outcomes in the microbiological intent-to-treat population in accordance with the 2019 FDA guidance. For descriptive comparison, we present the efficacy of ciprofloxacin 250 mg BID, 3d vs sulopenem 500 mg BID, 5d in the 2020 SURE-1 trial (also conducted in accordance with FDA guidance) alongside historical efficacy data for ciprofloxacin. Results Re-analysis of data from the trial of pivmecillinam and norfloxacin showed microbiological responses for pivmecillinam and norfloxacin of 64% and 79%, respectively. Microbiological responses were higher, 75% for pivmecillinam and 91% for norfloxacin, in the original analysis. For clinical response, re-analysis showed 75% for pivmecillinam and 88% for norfloxacin, while historical data were 82% and 88%, respectively. In the SURE-1 trial, the microbiological response of patients assessed at Day 12 was 76.6% for sulopenem and 79.1% for ciprofloxacin. In a 2002 publication, bacterial eradication at 4 to 11 days after treatment was 93.7% for ciprofloxacin 250 mg, a higher response rate than that reported in SURE-1. For clinical response, rates were 78.7% for ciprofloxacin in SURE-1 and 92.7% for the historical ciprofloxacin data. Conclusion When assessed in accordance with the 2019 FDA guidance, clinical and microbiological efficacy of both fluoroquinolones and β-lactam antibiotics appears lower than has been published in the past. Healthcare providers should be aware that newer antibiotics may appear to have a lower efficacy than older antibiotics due to the application of more stringent definitions in the FDA guidance. Disclosures Anne Santerre Henriksen, MS, Advanz (Consultant)Shionogi BV (Consultant)UTILITY Therapeutics (Consultant) Lindsay Nicolle, MD, Entos (Consultant)GSK (Consultant)Iterum (Consultant)Utility Therapeutics (Consultant) Anita F. Das, PhD, Adagio Therapeutics, Inc. (Consultant)

Patient and encounter characteristics found to be significantly associated with non-specific symptoms, p < 0.05.
Conclusion. Symptoms not specific to the urinary tract are the most frequently reported symptoms in patients with NB and encounters with a UTI diagnosis. Change in urine odor/color were reported often; however, guidelines recommend against using these for UTI diagnosis. Providers should ensure that alternate sources of non-specific symptoms are evaluated prior to attributing them to UTI. Antibiotic stewardship interventions targeted to physical medicine and rehabilitation (PM&R) and primary care providers in inpatient settings may improve UTI diagnosis in patients with NB.
Disclosures Background. In 2019, the FDA issued guidance on drug development for treatment of UTIs. To explore the impact of this guidance, we compared clinical and microbiological outcomes of the fluoroquinolones norfloxacin and ciprofloxacin and the β-lactams pivmecillinam and sulopenem for treatment of uUTIs from original publications versus recent analyses conducted in accordance with the FDA guidance.
Methods. The efficacy of pivmecillinam 400 mg twice daily (BID), 3 days (3d) versus norfloxacin 400 mg BID, 3d was reported in a 2002 publication. Patient-level data were used to re-analyze clinical and microbiological outcomes in the microbiological intent-to-treat population in accordance with the 2019 FDA guidance. For descriptive comparison, we present the efficacy of ciprofloxacin 250 mg BID, 3d vs sulopenem 500 mg BID, 5d in the 2020 SURE-1 trial (also conducted in accordance with FDA guidance) alongside historical efficacy data for ciprofloxacin.
Results. Re-analysis of data from the trial of pivmecillinam and norfloxacin showed microbiological responses for pivmecillinam and norfloxacin of 64% and 79%, respectively. Microbiological responses were higher, 75% for pivmecillinam and 91% for norfloxacin, in the original analysis. For clinical response, re-analysis showed 75% for pivmecillinam and 88% for norfloxacin, while historical data were 82% and 88%, respectively. In the SURE-1 trial, the microbiological response of patients assessed at Day 12 was 76.6% for sulopenem and 79.1% for ciprofloxacin. In a 2002 publication, bacterial eradication at 4 to 11 days after treatment was 93.7% for ciprofloxacin 250 mg, a higher response rate than that reported in SURE-1. For clinical response, rates were 78.7% for ciprofloxacin in SURE-1 and 92.7% for the historical ciprofloxacin data.
Conclusion. When assessed in accordance with the 2019 FDA guidance, clinical and microbiological efficacy of both fluoroquinolones and β-lactam antibiotics appears lower than has been published in the past. Healthcare providers should be aware that newer antibiotics may appear to have a lower efficacy than older antibiotics due to the application of more stringent definitions in the FDA guidance.
Disclosures Background. Urinary tract infections (UTIs) disproportionately affect women and are a substantial burden on healthcare systems. We assessed the effect of antibiotic (AB) switching on UTI recurrence, healthcare resource use (HRU), and related costs among adolescent and adult females in the US with uncomplicated UTIs (uUTIs).
Methods. This retrospective cohort study used US Optum claims data (United Healthcare, January 1, 2013-December 31, 2018). Eligible patients were females ≥ 12 years of age with an acute uUTI diagnosis at outpatient or emergency department (ED) visit (index date) and an oral AB prescription within ± 5 days of index. Patients with recurrent UTIs (rUTIs), defined as 2 UTI diagnoses (including index) in 6 months or ≥ 3 UTI diagnoses (including index) in 12 months, were included; those with complicated UTI were excluded. Patients were assigned to two groups: AB switch (≥ 2 filled prescriptions of different AB within 28 days post index [uUTI episode]) and no AB switch.
Results. In 5870 eligible patients (mean age 44.5 years; 76.6% White), ciprofloxacin (CIP; 38.6%), nitrofurantoin (NFT; 31.4%), and trimethoprim-sulfamethoxazole (TMP-SMX; 25.6%) were the most commonly prescribed first-line ABs at index, and 567 (9.7%) patients switched AB. CIP was switched to NFT and TMP-SMX in 2.0% and 1.7% of patients, respectively. NFT was switched to CIP and TMP-SMX in 2.6% and 1.5% of patients, respectively. TMP-SMX was switched to CIP and NFT in 3.0% and 2.4% of patients, respectively. During index visit, the AB switch group had higher mean ambulatory care and pharmacy claims (both p < 0.001), and higher total mean HRU costs ($2186.4) per patient compared with the no switch group ($1508.8; p = 0.011). More patients had rUTI in the AB switch group (18.9%) versus the no switch group (14.2%; p < 0.001), and more had ED visits in the AB switch group than the no switch group (p < 0.0001) ( Table 1). During follow-up, the AB switch group had a higher mean number of uUTI episodes per patient (p < 0.001; Table 1), and more patients had UTI-related ED visits (10.8%) compared with the no switch group (7.7%; p = 0.010; Table 2).