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Background In the past 10 years, there has been a substantial increase in antimicrobial resistance among uropathogens in community-acquired uncomplicated urinary tract infections (uUTIs), including extended spectrum β-lactamase producing (ESBL+) Enterobacterales and multidrug resistance. This study examined urine isolates from female outpatients in the United States (US) for co-resistance among Escherichia coli (E. coli). Methods This was a retrospective, cross-sectional study of 30-day non-duplicate E. coli urine isolates (first isolates collected within a 30-day period) from female outpatients (≥ 12 years of age) at 304 US facilities. Included patients had ≥ 3 months of data from 2011 to 2019 (Becton, Dickinson and Company [BD] Insights Research Database). Urine-isolated E. coli were defined as ESBL+ by 1) commercial panel or 2) not susceptible (NS; intermediate/resistant) to ceftriaxone, cefotaxime, ceftazidime, or cefepime), or NS to any of: fluoroquinolones (FQs), trimethoprim/sulfamethoxazole (SXT), or nitrofurantoin (NFT). Microbiological co-resistance phenotypes were characterized in isolates NS to ≥ 2 of the 4 resistance phenotypes assessed. Results In total, 856,918 unique isolates were evaluated. Co-resistance data are shown in the Table. Of ESBL+ isolates (96,306), 72.4% were co-resistant to FQ, 56.7% to SXT, and 11.9% to NFT; 6.8% had all 4 phenotypes. For FQ NS isolates (319,354), 21.8% were also ESBL+, 51.6% were co-resistant to SXT, 8.0% were co-resistant to NFT, and 2.0% had all 4 phenotypes. Among SXT NS isolates (384,304), 14.2% were also ESBL+, 42.9% were co-resistant to FQ, 6.8% were co-resistant to NFT, and 1.7% had all 4 phenotypes. Finally, for NFT NS isolates (56,954), 20.1% were ESBL+, 44.7% were co-resistant to FQ, 46.0% were co-resistant to SXT, and 11.5% had all 4 phenotypes. Table.Co-resistance phenotype combinations among urine-isolated Escherichia coli (2011–2019)In total, 856,918 non-duplicate (30-day) Escherichia coli isolates were evaluated.Note: Some isolates had overlapping susceptibilities/antimicrobial resistance types, hence individual phenotype totals do not reflect total number of isolates evaluated.Abbreviations: ESBL+, extended spectrum β-lactamase-producing (by commercial panel or not susceptible to ceftriaxone, cefotaxime, ceftazidime or cefepime); FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion Among urine-isolated E. coli, there was a high prevalence of co-resistance, particularly for ESBL+ isolates where co-resistance to FQ was > 70%. The availability of effective oral treatments for uUTI is limited by uropathogen antibiotic resistance. These data may help inform appropriate empiric prescribing practices to optimize the treatment of uUTI, mitigate multiple drug exposure for a uUTI event, and potentially influence long-term resistance patterns among E. coli. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Janet Watts, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

Background Infections caused by extended spectrum β-lactamase producing Enterobacterales (ESBLs), as well as antimicrobial resistance (AMR) and multi-drug resistance among uncomplicated urinary tract infections (uUTIs) in outpatients have risen in the past decade. The study objective was to determine the prevalence and geographic distribution of AMR among Klebsiella pneumoniae (K. pneumoniae) isolates in urine from female outpatients in the United States (US). Methods A retrospective, cross-sectional study of non-duplicate urine isolates from female outpatients (≥ 12 years of age) at 304 facilities, with ≥ 3 months of data, including initial isolates with distinct susceptibility patterns within 30 days of index urine samples, were used to assess regional AMR in 2019, and AMR trends from 2011 to 2019 (BD Insights Research Database, Franklin Lakes, NJ). K. pneumoniae isolates were identified as ESBL-positive (ESBL+) (confirmed by commercial panel or not susceptible [NS] to ceftriaxone, cefotaxime, ceftazidime, or cefepime), or NS if intermediate/resistant to any of the following: nitrofurantoin (NFT), trimethoprim/sulfamethoxazole (SXT), or fluoroquinolones (FQs). AMR prevalence and variation across US census regions was evaluated using logistic regression (with covariate adjustment) and generalized estimating equations. Results 44,056 non-duplicate K. pneumoniae isolates were evaluated in 2019 (Figure). For all microbiological phenotypes, there was significant variation in resistance for K. pneumoniae across all US census regions (p< 0.0001). Among 250,719 isolates evaluated from 2011 to 2019, AMR prevalence increased for all studied antimicrobials except for NFT NS (all p< 0.0041; Table). There was an increase in adjusted AMR rates by age groups with higher AMR rates for females ≥ 55 versus < 55, except for NFT, which showed the highest resistance in those aged < 55. Figure.Prevalence of antimicrobial resistance in Klebsiella pneumoniae isolates in 2019Abbreviations: ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole.Table.Klebsiella pneumoniae: model-estimated trends of relative average annual percentage change of antimicrobial resistance over time (2011 to 2019), by patient age, and by census region (N=250,719 isolates)All p values were p< 0.0001 apart from NFT trend over years, which was p=0.0041.*Relative average annual percentage change in resistance rate.Abbreviations: CDC, Centers for Disease Control and Prevention; CI, confidence interval; ESBL+, extended spectrum β-lactamase-positive or not susceptible to ceftriaxone, cefotaxime, ceftazidime, or cefepime; FQ, fluoroquinolone; NFT, nitrofurantoin; NS, not susceptible; SXT, trimethoprim/sulfamethoxazole. Conclusion AMR prevalence in 2019 among non-duplicate K. pneumoniae isolates from urine in outpatients was notable. There were significant regional differences in resistance rates, which were higher in those aged ≥ 55 years, except for NFT. These analyses inform, and may be used to optimize, empiric treatment of uUTI. Disclosures Keith S. Kaye, MD, MPH, Allecra: Advisor/Consultant|GlaxoSmithKline plc.: Receiving symposia honoraria|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502|Merck: Advisor/Consultant|qpex: Advisor/Consultant|Shionogi: Grant/Research Support|Spero: Advisor/Consultant Vikas Gupta, PharmD, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Aruni Mulgirigama, MBBS, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Ashish V. Joshi, PhD, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study Nicole E. Scangarella-Oman, MS, GlaxoSmithKline plc.: Employee and shareholder Kalvin Yu, MD, FIDSA, Becton, Dickinson and Company: Employee of, and shareholder in, Becton, Dickinson and Company, and the company received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Gang Ye, PhD, Becton, Dickinson and Company: Employee of Becton, Dickinson and Company, and received funding from GlaxoSmithKline plc. to conduct this study|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502 Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc.: Employee and shareholder|GlaxoSmithKline plc.: GlaxoSmithKline plc.-sponsored study 212502.

Background Increasing antimicrobial resistance makes treating uncomplicated urinary tract infections (uUTIs) difficult. We compared whether adverse short-term outcomes among US female patients were more common when initial antimicrobial therapy did not cover the causative uropathogen. Methods This retrospective cohort study used data from female outpatients aged ≥12 years, with a positive urine culture and dispensing of an oral antibiotic ±1 day from index culture. Isolate susceptibility to the antimicrobial initially dispensed, patient age, and history of antimicrobial exposure, resistance, and all-cause hospitalization within 12 months of index culture were evaluated for associations with adverse outcomes during 28-day follow up. Outcomes assessed were new antimicrobial dispensing, all-cause hospitalization, and all-cause outpatient emergency department/clinic visits. Results Of 2366 uUTIs, 1908 (80.6%) were caused by isolates susceptible and 458 (19.4%) by isolates not susceptible (intermediate/resistant) to initial antimicrobial treatment. Within 28 days, patients with episodes caused by not susceptible isolates were 60% more likely to receive a new antimicrobial versus episodes with susceptible isolates (29.0% vs 18.1%; 95% confidence interval, 1.3–2.1; P < .0001). Other variables associated with new antibiotic dispenses within 28 days were older age, prior antimicrobial exposure, or prior nitrofurantoin-not-susceptible uropathogens (P < .05). Older age, prior antimicrobial-resistant urine isolates, and prior hospitalization were associated with all-cause hospitalization (P < .05). Prior fluoroquinolone-not-susceptible isolates or oral antibiotic dispensing within 12 months of index culture were associated with subsequent all-cause outpatient visits (P < .05). Conclusions New antimicrobial dispensing within the 28-day follow-up period was associated with uUTIs where the uropathogen was not susceptible to initial antimicrobial treatment. Older age and prior antimicrobial exposure, resistance, and hospitalization also identified patients at risk of adverse outcomes.

Background Uncomplicated urinary tract infection (uUTI) is predominantly caused by Escherichia coli, which has increasing antimicrobial resistance (AMR) at the United States (US)-community level. As uUTI is often treated empirically, assessing AMR is challenging, and there are limited contemporary data characterizing period prevalence in the US. Methods This was a retrospective study of AMR using Becton, Dickinson and Company Insights Research Database (Franklin Lakes, New Jersey, US) data collected 2011–2019. Thirty-day, nonduplicate Escherichia coli urine isolates from US female outpatients (aged ≥12 years) were included. Isolates were evaluated for nonsusceptibility (intermediate/resistant) to trimethoprim-sulfamethoxazole, fluoroquinolones, or nitrofurantoin, and assessed for extended-spectrum β-lactamase production (ESBL+) and for ≥2 or ≥3 drug-resistance phenotypes. Generalized estimating equations were used to model AMR trends over time and by US census region. Results Among 1 513 882 E. coli isolates, the overall prevalence of isolates nonsusceptible to trimethoprim-sulfamethoxazole, fluoroquinolones, and nitrofurantoin was 25.4%, 21.1%, and 3.8%, respectively. Among the isolates, 6.4% were ESBL+, 14.4% had ≥2 drug-resistance phenotypes, and 3.8% had ≥3. Modeling demonstrated a relative average yearly increase of 7.7% (95% confidence interval [CI], 7.2–8.2%) for ESBL+ isolates and 2.7% (95% CI, 2.2–3.2%) for ≥3 drug-phenotypes (both P, This study provides contemporary data on the prevalence and trends of antimicrobial resistance among E. coli isolated from female outpatient urine cultures in the United States, 2011–2019. The prevalence of antimicrobial resistance is high and increasing for key phenotypes.

Background Antimicrobial resistance is an urgent global healthcare concern. Beyond carbapenems as broad-spectrum, often ‘last resort’ antibiotics, oral penem antibiotics currently are approved only in Japan and India, used for the treatment of indications including urinary tract infections (UTIs). Exploring oral penem use to better understand the impact of antibiotic resistance on public health would help inform the management of infectious diseases, including UTIs. Scoping Review Methodology This scoping review investigated the impact of faropenem and other oral penems on Enterobacterales infection treatment and evaluated evidence for faropenem resistance and cross-resistance to carbapenems. PubMed, Embase, J-STAGE and CiNii were searched for relevant English- or Japanese-language articles published between 1 January 1996 and 6 August 2021. Key Findings From 705 unique publications, 29 eligible articles were included (16 in vitro studies; 10 clinical trials; 2 in vitro and in vivo studies; and 1 retrospective medical chart review). Limited evidence described faropenem to treat infectious disease; only four randomized clinical trials were identified. Faropenem dosing regimens varied broadly within and between indications. One study indicated potential dependence of penem efficacy on underlying antibiotic resistance mechanisms, while several studies reported UTI persistence or recurrence after faropenem treatment. In vitro MIC data suggested some potential bacterial resistance to faropenem, while limited clinical data showed resistance emergence after faropenem treatment. Preliminary in vitro evidence suggested faropenem resistance might foster cross-resistance to carbapenems. Overall, very limited clinical evidence describes faropenem for treating infectious diseases. Preclinical and clinical research investment and dedicated community surveillance monitoring is crucial for understanding faropenem treatment patterns, resistance and potential cross-resistance to carbapenems.

Active-controlled noninferiority studies are used to investigate novel agents for uncomplicated urogenital gonorrhea (uUGC) as placebo-controlled trials are unethical. A systematic literature review and meta-analysis were conducted to estimate the ceftriaxone and proxy-for-placebo microbiological treatment effect and determine an appropriate noninferiority margin for phase 3 trials.Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines were followed. To account for interstudy variability, a weighted, noniterative random-effects model was fitted using "R" software to estimate the microbiological response rate and 95% confidence intervals (CIs) for ceftriaxone and proxy-for-placebo (treatment with an antibiotic the isolate was subsequently confirmed resistant to, or spontaneous resolution without treatment). I2 , τ2 , and P values were computed and included in the meta-analysis forest plot.Seventeen studies were included in the meta-analysis; 14 reported ceftriaxone response in micro-intent-to-treat and microbiologically evaluable populations, and 3 reported proxy-for-placebo treatment response in uUGC (microbiologically evaluable population only). Microbiological treatment effect was estimated by subtracting the upper end of the CI for placebo from the lower end of the CI for ceftriaxone. Overall microbiological response was 98% (95% CI, 97-99) for ceftriaxone and 44% (95% CI, 34-54) for proxy-for-placebo, resulting in a microbiological treatment effect of 43%. A noninferiority margin of 15% preserved 65% of the ceftriaxone treatment effect, exceeding the 50% recommended per US Food and Drug Administration guidance for noninferiority studies.Results of this systematic literature review and meta-analysis could help inform the design, conduct, and analysis of future clinical studies in uUGC.

Background Increasing prevalence of antimicrobial resistance (AMR), including multidrug resistance (MDR), among Escherichia coli (E. coli) makes treatment of uncomplicated urinary tract infection (uUTI) difficult. We assessed risk factors for fluoroquinolone (FQ)-not-susceptible (NS) and MDR E. coli among US female outpatients. Methods This retrospective cohort study utilized data from female outpatients aged ≥ 12 years with E. coli positive urine culture and oral antimicrobial prescription ± 1 day from index. We assessed patient-level factors within 90 and 91–360 days prior to index as predictors of FQ NS (intermediate/resistant) and MDR (NS to ≥ 1 drug across ≥ 3 classes) E. coli: age, prior oral antimicrobial dispensing, prior AMR phenotypes, prior urine culture, and prior hospitalization. Results Among 1,858 outpatients with urine-isolated E. coli, 369 (19.9%) had FQ NS and 59 (3.2%) had MDR isolates. After multivariable adjustment, independent risk factors (p < 0.03) for FQ NS E. coli were older age, prior FQ NS isolates, prior dispensing of FQ, and dispensing of any oral antibiotic. Independent risk factors (p < 0.02) for MDR were prior extended-spectrum β-lactamase-producing isolates (ESBL+), prior FQ dispensing, and prior oral antibiotic dispensing. Conclusions In women with uUTI due to E. coli, prior dispensing of FQ or any oral antibiotic within 90 days predicted FQ NS and MDR urine E. coli. Prior urine culture with FQ NS isolates and older age were predictive of FQ NS E. coli. Prior ESBL+ was predictive of MDR E. coli. These data could help identify patients at risk for AMR E. coli and inform empiric prescribing.

INTRODUCTION AND OBJECTIVE:Short-term (28-day) health outcomes in females with uncomplicated urinary tract infection (uUTI) were assessed to determine if uropathogen infection not covered by initia...

Background Uncomplicated urinary tract infections (uUTI) account for a large proportion of primary care antibiotic (AB) prescriptions. This study assessed uUTI-related healthcare resource use (HRU) and costs in US females with a self-reported uUTI. Methods We surveyed US females aged ≥ 18 years who participated in web-based surveys (fielded August 28–September 28, 2020 by Dynata, EMI, Lucid/Federated, and Kantar Profiles). Participants had a self-reported uUTI ≤ 60 days prior, and took ≥ 1 oral AB for their uUTI. Those reporting signs of complicated UTI were excluded. HRU was measured via self-reported primary care provider (PCP), specialist, urgent care, emergency room (ER) visits, and hospitalizations. Direct costs were calculated as sum of self-reported and HRU monetized with Medical Expenditure Panel Survey estimates. Indirect costs were calculated via Work Productivity and Impairment metrics monetized with Bureau of Labor Statistics estimates. Participants were stratified by number of oral ABs prescribed (1/2/3+) and therapy appropriateness (1 AB [1st line/2nd line]/multiple [any line] AB) for most recent uUTI. Multivariable regression modeling was used to compare strata; 1:1 propensity score matching assessed uUTI burden vs matched population (derived from the 2020 National Health and Wellness Survey [NHWS]). Results In total, 375 participants were eligible for this analysis. PCP visits (68.8%) were the most common HRU. Across participants, there were an average of 1.46 PCP, 0.31 obstetrician/gynecologist, 0.41 urgent care and 0.08 ER visits, and 0.01 hospitalizations for most recent uUTI (Table 1). Total mean uUTI-related direct and indirect costs were &1289 and &515, respectively (Table 1). Adjusted mean total direct costs were significantly higher (Table 2) for participants in the ‘2 AB’ cohort vs the ‘1 AB’ cohort (&2090 vs &776, p < 0.0001), and for the ‘multiple AB’ vs ‘1 AB, 1st line’ cohorts (&1642 vs &875, p=0.002). Participants in the uUTI cohort reported worse absenteeism (+15.3%), presenteeism (+46.5%), overall work impairment (+52.4%), and impact on daily activities (+50.7%) vs NHWS cohort (p < 0.0001, Table 3). Table 1. Overall mean uUTI-related healthcare resource use, direct, and indirect cost data Table 2. Estimated uUTI-related direct costs stratified by (A) number of AB and (B) appropriateness of AB therapy used to treat last uUTI Table 3. Mean Work Productivity and Activity Impairment data for uUTI and NHWS cohorts Conclusion Inadequate treatment response, evident by multiple AB use, was associated with an increase in uUTI-related costs, including productivity loss. Disclosures Jeffrey Thompson, PhD, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Jonathon Wright, BSc, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background Gonorrhea (GC) is a major public health threat in the US. The Centers for Disease Control and Prevention (CDC) estimated direct healthcare costs of &271 million in 2018. CDC 2015 guidelines (applicable up to December 18, 2020) recommended cephalosporin plus azithromycin for GC. We used real-world data to assess patterns of inappropriate or suboptimal (IA/SO) or appropriate and optimal (AP&OP) antibiotic (AB) prescription (by CDC 2015 guidelines), and related healthcare costs, in US patients with uncomplicated urogenital GC (uUGG) diagnosed from July 1, 2013–June 30, 2018. Methods A retrospective cohort study of IBM MarketScan data (commercial/Medicare claims) in patients ≥ 12 years old with uUGG. Eligible patients had an AB prescription ±5 days of uUGG diagnosis (index date) and continuous health-plan enrollment with ≥ 6 months’ baseline/≥ 12 months’ follow-up data. Patients with complicated urogenital GC were excluded. Patients were stratified by AB prescription (IA/SO or AP&OP; defined in Table 1) during the first uUGG episode (ie, within 30 days of index). Generalized linear models were used for multivariate analysis. Table 1. Definitions of appropriateness of AB prescriptions Results Of 2847 patients with uUGG (58.5% male), 77.1% had an IA/SO prescription (mostly due to IA AB class [~82.0%] and duration [24.0%]), while only 22.9% had an AP&OP prescription; uUGG episodes were more frequent with IA/SO (n=2386) than AP&OP (n=714) prescriptions during follow-up. Patients with IA/SO prescriptions had higher GC-related total adjusted costs per patient (PP) per index episode (&196) vs those with AP&OP prescriptions (&124, p < 0.0001; Figure). Patients with IA/SO prescriptions also had higher GCrelated total adjusted costs PP during follow-up (&220) vs those with AP&OP prescriptions (&148, p < 0.0001), mostly driven by higher outpatient ambulatory and emergency room (ER) adjusted costs with IA/SO (&148 and &71, respectively) vs AP&OP prescriptions (&129 and &12, respectively, p ≤ 0.0152; Figure). ER visits PP at index and during follow-up were higher with IA/SO vs AP&OP prescriptions (p < 0.0001; Table 2). Figure. GC-related costs per patient with uUGG, stratified by appropriateness of AB prescription* Table 2. GC-related HRU per patient with uUGG, stratified by AB prescription Conclusion Most patients with uUGG were not prescribed treatments in accordance with CDC 2015 guidelines. High IA/SO AB prescriptions and associated healthcare costs suggest an unmet need for improved prescribing practices for uUGG in the US. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Ziyu Lan, MSc, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

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). Table 1. Primary outcomes of uncomplicated UTI outpatients during January 1, 2013–December 31, 2018, stratified by any switch in AB use during index episode Table 2. Primary outcomes of uncomplicated UTI outpatients during January 1, 2013–December 31, 2018, stratified by any switch in AB use during 12-month follow-up Conclusion US females with uUTI who switched AB had more rUTI cases and increased overall costs and HRU compared with those who did not switch AB, suggesting an unmet need for improved prescribing practices. Disclosures Rena Moon, MD, Premier Applied Sciences, Premier Inc. (Employee) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Alex Kartashov, PhD, Premier Applied Sciences, Premier Inc. (Employee) Ning Rosenthal, MD, Premier Applied Sciences, Premier Inc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background Uncomplicated urinary tract infections (uUTI) are among the most common infections in women; however, there are few data on the impact of uUTIs on daily activity and health-related quality of life (HRQoL). Methods This was a prospective, cross-sectional survey of US females aged ≥ 18 years with a self-reported uUTI in the 60 days prior to participation. Participants were included if they received oral antibiotic treatment and participated in surveys fielded by Dynata, Lucid/Federated, or Kantar Profiles. See Table 1 for inclusion/exclusion criteria. Study objectives were to describe activity impairment (using the Activity Impairment Assessment [AIA]) and HRQoL (assessed with Short Form 36 version 2, Physical Component Score [PCS], Mental Component Score [MCS], and health utility index [SF-6D]) associated with uUTI. After screening, participants completed an online questionnaire on their most recent uUTI. Outcomes were reported with descriptive statistics, chi-squared tests, and t-tests. Analysis of HRQoL used 1:1 propensity score matching to compare to a matched US population from the 2020 National Health and Wellness Survey. Table 1. Inclusion and exclusion criteria Results In total, 375 participants completed the questionnaire. Common impaired activities were: sexual intercourse (66.9%), sleep (60.8%), exercise (52.3%), housework (51.5%), and social activities (46.9%; Table 2). Overall mean AIA score was 11.1/20 (higher score = more impairment). Most participants (58.7%) had a PCS that was the same or better than the matched population, while for MCS, most participants (52.8%) had scores well below the matched population average. Overall PCS, MCS, and SF-6D composite scores were 46.5, 40.0, and 0.63, respectively; these outcomes were significantly worse compared to the matched population, most notably MCS (Table 3). Stratification by number of antibiotics used revealed statistically significant differences in the effect of uUTI on exercise, PCS, SF-6D (based on use of 1 or ≥ 3 therapies), and on sleep (based on use of 2 or ≥ 3 therapies; Table 4). Table 2. Activities impacted by uUTI Table 3. Matched analysis of SF-36v2-measured HRQoL outcomes Table 4. Outcomes stratified by number of oral antibiotics used to treat last uUTI Conclusion uUTIs are significantly associated with adverse patient outcomes for daily activities and HRQoL, compounded by suboptimal treatment evident by the use of multiple antibiotics. MCS was notably affected, which is important as this is not often studied in uUTI. Disclosures Jeffrey Thompson, PhD, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Jonathon Wright, BSc, Kantar Health (Employee, Employee of Kantar Health, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background Urinary tract infections (UTIs) are associated with significant morbidity and economic burden. Nitrofurantoin (NFT) and fosfomycin are among the first-line treatments for uncomplicated UTI (uUTI) recommended by Infectious Diseases Society of America (IDSA) 2011 guidance. We used real-world data (RWD) to assess patterns of appropriate and optimal (AP&OP) and inappropriate or suboptimal (IA/SO) antibiotic (AB) prescribing (RX), and related healthcare resource use (HRU) and costs, in US uUTI patients with high-risk comorbid conditions. Methods This was a retrospective cohort study of RWD (IBM MarketScan, commercial/Medicare Supplemental claims January 1, 2014–December 31, 2017) in females ≥ 12 years of age with uUTI, who had an oral AB prescription ± 5 days of uUTI diagnosis (index date) and continuous health-plan enrollment ≥ 1 year pre-/post-index date. Patients were stratified into high-risk cohorts (Table 1) and by AB RX (AP&OP and IA/SO) during first uUTI episode (within 28 days of index). AP&OP RX followed IDSA guidance, IA RX did not; SO RX was considered a proxy for treatment failure (e.g., AB switch or a second UTI diagnosis [acute care setting] in index episode). Sample size was balanced via random match selection, AP&OP:IA/SO ratio 1:5 (age and region). uUTIrelated HRU and costs were compared between cohorts (at index episode and 1-year follow-up) via multivariable analysis. Table 1. High-risk cohorts identified in the study Results IA/SO AB RX was highest in the elderly cohort (94.3%, likely influenced by renal impairment/no NFT RX in this group) and > 90% in other cohorts; AP&OP AB RX was highest in the postmenopausal cohort (9.0%). IA/SO AB RX in all cohorts was associated with significantly higher uUTI-related HRU (outpatient visits and pharmacy claims) per index episode/during follow-up versus AP&OP AB RX (p ≤ 0.0237, Table 2). IA/SO AB RX in all cohorts was associated with significantly higher adjusted total costs per index episode/during follow-up versus AP&OP AB RX (p < 0.05; Table 3). Table 2. uUTI-related HRU* per patient according to high-risk cohort and stratified by AB RX Table 3. uUTI-related costs* per patient according to high-risk cohort and stratified by AB RX Conclusion Over 90% of females in each high-risk cohort identified had IA/SO AB RX (outside IDSA 2011 guidance for uUTI treatment), leading to high HRU and cost burden. This suggests an unmet need for uUTI symptom relief, new treatments, training, and improved RX practices in the US and, furthermore, a need for additional research in this area. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background Uncomplicated urinary tract infections (uUTI) are one of the most common bacterial infections in women. Understanding unmet needs of physicians in diverse healthcare systems is important for developing novel uUTI treatment (tx). Methods A cross-sectional survey of physicians in the US and Germany (DE). Physicians were recruited via specialist panel and the survey was piloted (1 US, 1 DE physician) prior to recruitment. Primary objectives were understanding physician tx goals, management approaches, and prescribing patterns for uUTI. Secondary objectives included understanding perceptions of uUTI impact on patients and awareness of antibiotic (AB) resistance. Descriptive statistics were used for analysis. See Table for inclusion/exclusion criteria. Table. Physician inclusion and exclusion criteria Results Overall, 300 physicians (200 US, 100 DE) were surveyed. Symptom relief was in the top 3 (of 5) most important outcomes for ≥ 90% of physicians (US and DE); clearing infection was a top 3 outcome for 85% of US and 60% of DE physicians (Fig. 1). Physicians estimated ~20% of patients do not achieve complete relief from initial AB tx. Generally, urinalysis, dip stick, and symptom review were most commonly used in diagnosis, with culture and AB susceptibility tests mostly used to aid tx decisions (Fig. 2). For first-line AB, US physicians reported trimethoprim-sulfamethoxazole (TMP-SMX; 76%) and nitrofurantoin (57%) as most prescribed; in DE, fosfomycin (61%) and TMP-SMX (50%) were prescribed most. In both countries, ciprofloxacin (US 51%, DE 45%) was most prescribed after ≥ 2 tx failures. On a scale of “very poor” (1) to “exceptional” (7) for tx and management of uUTI, 58% of US physicians gave TMP-SMX a 6 or 7, and 62% of DE physicians gave fosfomycin a 6 or 7. More than 33% of physicians believed patients’ quality of life was greatly impacted by 1 tx failure, rising to 60% of physicians for 2 tx failures, and 73% for ≥ 3. Most physicians (72% US, 83% DE) agreed that development of AB resistance was serious (Fig. 3), but fewer (56% US, 46% DE) were confident in their knowledge of AB resistance. Figure 1. Treatment goal considered in the top 3 most important goals by physicians for managing patients with uUTI Figure 2. Use of diagnosis (A) and treatment decision (B) aids Figure 3. Physicians’ opinions on antibiotic resistance Conclusion Symptom relief was the primary uUTI tx goal for physicians. Physicians recognized that patients are greatly impacted by tx failure and AB resistance is a serious problem, but many were not confident or had insufficient information on AB resistance. Disclosures Megan O’Brien, BA, Adelphi Real World (Employee, Employee of Adelphi Real World, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Laura Terry, MSc, Adelphi Real World (Employee, Employee of Adelphi Real World, which received funding from GlaxoSmithKline plc. to conduct this study) Gavin Taylor-Stokes, MBA, Adelphi Real World (Employee, Employee of Adelphi Real World, which received funding from GlaxoSmithKline plc. to conduct this study) James Pike, B.Sc. Hons., M.Phil., Adelphi Real World (Employee, Employee of Adelphi Real World, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background The first cases of extensively drug resistant gonorrhoea were recorded in the United Kingdom in 2018. There is a public health need for strategies on how to deploy existing and novel antibiotics to minimise the risk of resistance development. As rapid point-of-care tests (POCTs) to predict susceptibility are coming to clinical use, coupling the introduction of an antibiotic with diagnostics that can slow resistance emergence may offer a novel paradigm for maximising antibiotic benefits. Gepotidacin is a novel antibiotic with known resistance and resistance-predisposing mutations. In particular, a mutation that confers resistance to ciprofloxacin acts as the ‘stepping-stone’ mutation to gepotidacin resistance. Aim To investigate how POCTs detecting Neisseria gonorrhoeae resistance mutations for ciprofloxacin and gepotidacin can be used to minimise the risk of resistance development to gepotidacin. Methods We use individual-based stochastic simulations to formally investigate the aim. Results The level of testing needed to reduce the risk of resistance development depends on the mutation rate under treatment and the prevalence of stepping-stone mutations. A POCT is most effective if the mutation rate under antibiotic treatment is no more than two orders of magnitude above the mutation rate without treatment and the prevalence of stepping-stone mutations is 1–13%. Conclusion Mutation frequencies and rates should be considered when estimating the POCT usage required to reduce the risk of resistance development in a given population. Molecular POCTs for resistance mutations and stepping-stone mutations to resistance are likely to become important tools in antibiotic stewardship.

Background Despite well-established guidelines for urinary tract infection (UTI) treatment, prescribing practices vary. We examined the association between inappropriate (IA) or suboptimal (SO) antibiotic (AB) prescribing (RX) and hospitalization, healthcare resource use (HRU), and costs among patients with uncomplicated UTI (uUTI) in the US. Methods This retrospective cohort study used linked Premier Healthcare/Optum claims data from female outpatients (≥ 12 years old) with a uUTI diagnosis (January 1, 2013 to December 31, 2018). Patients with complicated UTIs (eg, urological abnormalities, medications/procedures associated with complicated UTI, or intravenous AB receipt at index) were excluded. HRU and costs between patients with IA/SO and appropriate and optimal (AP&OP) AB RX (defined in Table 1) were assessed from Optum claims data during index episode (within 28 days of index) and 12-month follow-up. Table 1. Definitions of appropriateness of AB RX Results Of 5870 patients, 1856 (31.6%) had IA and 1255 (21.4%) had SO AB RX. Patients with IA/SO AB RX (47.1%) were older and more likely to have a Charlson Comorbidity Index score > 0 than those with AP&OP AB RX (52.9%; Table 2). During index episode, mean ambulatory care and pharmacy claims were significantly higher for IA/SO versus AP&OP AB RX (8.0 vs 6.3, 3.3 vs 2.6, respectively; p < 0.01), and total HRU cost per patient was higher for IA/SO (&2616) versus AP&OP AB RX (&649; p < 0.01). During follow-up, 267 (9.7%) patients with IA/SO AB RX had a UTI-related emergency department (ED) visit versus 202 (6.5%) patients with AP&OP AB RX (p < 0.001). Mean UTI-related HRU costs were significantly higher for IA/SO (&5048) versus AP&OP AB RX (&3633; p = 0.01). After adjusting for patient characteristics, patients with IA/SO AB RX were 40% more likely than those with AP&OP AB RX to have a UTI-related ED visit (odds ratio 1.40; 95% confidence interval 1.15–1.71) during follow-up (Table 3). Adjusted HRU costs for IA/SO AB RX (vs AP&OP) were numerically higher for index uUTI episode (by &1772), and UTI-related (by &1102) and all-cause (by &1528) charges during follow-up (Figure). Table 2. Baseline characteristics of patients stratified by appropriateness of AB RX Table 3. Associations of AP&OP AB RX and HRU charges for index episode and 12-month follow-up Figure. Total 12-month UTI-related and all-cause visit charges (adjusted), stratified by appropriateness of AB RX at index and during follow-up Conclusion IA/SO AB RX was associated with higher overall and UTI-related HRU and costs during index episode and 12-month follow-up, highlighting a need for education on applying prescription guidelines and the use of culture-based RX. Disclosures Rena Moon, MD, Premier Applied Sciences, Premier Inc. (Employee) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Daniel C. Gibbons, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Alex Kartashov, PhD, Premier Applied Sciences, Premier Inc. (Employee) Ning Rosenthal, MD, Premier Applied Sciences, Premier Inc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background Uncomplicated urinary tract infection (uUTI) is often treated empirically without antibiotic (AB) susceptibility testing; however, antimicrobial-resistant bacteria could lead to suboptimal treatment and progression to complicated UTI (cUTI). We examined the likelihood of uUTI progression to cUTI in patients with susceptible and non-susceptible uropathogens. Methods We performed a retrospective cohort study using data from a large Mid-Atlantic US integrated delivery network’s electronic health records from July 1, 2016 to March 31, 2020. Patients included were female, aged ≥ 12 years with incident uUTI (diagnosis code or urine culture), and given an oral AB ± 5 days of diagnosis and ≥ 1 antibiotic susceptibility test. The primary outcome was progression to cUTI, defined as: new fever, nausea, or vomiting, in addition to uUTI symptoms; or receipt of intravenous antibiotic 3–28 days after index uUTI. Probability of progression to cUTI was assessed comparing patients with non-susceptible and susceptible isolates, with 1:1 propensity score matching. Patients retained for analysis had a nonzero predicted probability of being in the case and control group and were retained for analysis only if there were patients in the mirror group with similar propensity scores. Data were analyzed with logistic regression. Sensitivity analyses were performed to test the robustness of the primary analysis (Table). Results A total of 2565 patients were included: 1030 (40.2%) had non-susceptible isolates and 1535 (59.8%) had susceptible isolates. Mean age was 43.5 years and 59.5% of the cohort was White. After propensity score matching, patients with non-susceptible isolates were more than twice as likely to progress to cUTI versus patients with sensitive isolates (10.7% versus 4.9%; odds ratio, 2.35; p < 0.001; Figure). In sensitivity analyses, patients with non-susceptible isolates remained significantly more likely to progress to cUTI (p ≤ 0.009), excluding those receiving fluoroquinolones only (Table). Figure. Probability of progression to cUTI Table. Sensitivity analyses of the probability of uUTI progressing to cUTI in patients with non-susceptible versus susceptible isolates (matched population) Conclusion Patients with uUTI and AB-resistant isolates were significantly more likely to progress to cUTI than those with susceptible isolates. This finding highlights the need for greater understanding of antimicrobial resistance and has implications for the clinical management of uUTI. Disclosures Jason Shafrin, PhD, Precision Medicine Group (Employee, Former employee of Precision Medicine Group, which received funding from GlaxoSmithKline plc. to conduct this study) Alen Marijam, MSc, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Katie Everson, MSc, Precision Medicine Group (Employee, Employee of Precision Medicine Group, which received funding from GlaxoSmithKline plc. to conduct this study) Rifat Tuly, MPH, Precision Medicine Group (Employee, Employee of Precision Medicine Group, which received funding from GlaxoSmithKline plc. to conduct this study) Peter Rosenquist, MSc, Precision Medicine Group (Employee, Employee of Precision Medicine Group, which received funding from GlaxoSmithKline plc. to conduct this study) Michael Gillam, MD, MedStar Health (Employee, Employee of MedStar Health and received funding from GlaxoSmithKline plc. through Precision Medicine Group to conduct this study) Maria Elena Ruiz, MD, Nothing to disclose

Background Urinary tract infections (UTIs) are the most common outpatient infection requiring medical care in the US; but, despite Infectious Diseases Society of America 2011 guidelines for treating uncomplicated UTI (uUTI), variation in prescribing practices still exists. Few studies have used real-world data (RWD) to evaluate uUTI-associated healthcare resource use (HRU) and costs. We examined HRU and direct costs associated with appropriate and optimal (AP&OP) and inappropriate or suboptimal (IA/SO) antibiotic (AB) prescribing in females with uUTI using US RWD. Methods This retrospective cohort study used RWD from IBM MarketScan (commercial/Medicare claims) to examine uUTI-related HRU and costs (inpatient, emergency room, outpatient, pharmacy) per index uUTI episode and during 1-year follow-up among females (age ≥ 12 years) diagnosed with uUTI from July 1, 2013–December 31, 2017 (index date). Patients had an oral AB prescription ± 5 days of the index date, and continuous health plan enrollment ≥ 6 months pre/1 year post-index date; those with complicated UTI were excluded. Patients were stratified by AB prescription as follows: AP&OP = guideline-compliant and correct duration; IA/SO = guideline non-compliant/incorrect duration or re-prescription/switch within 28 days. Results The study included 557,669 patients. In the commercial population (n=517,664, mean age 37.7 years), fewer patients were prescribed AP&OP (11.8%) than IA/SO (88.2%) ABs, a trend also seen in the Medicare population (n=40,005, mean age 74.5 years). In both populations, adjusted average numbers of uUTI-related ambulatory visits and pharmacy claims were lower for the AP&OP cohort than the IA/SO cohort during index episode and 1-year followup (p < 0.0001, Table 1). In the commercial population, total adjusted uUTI-related costs were &194 (AP&OP) versus &274 (IA/SO; p < 0.0001); in the Medicare population, total adjusted uUTI-related costs were &253 (AP&OP) versus &355 (IA/SO; p < 0.0001) (Table 2). Table 1. uUTI-related HRU for commercial and Medicare populations calculated using the GLM model Table 2. uUTI-related costs for commercial and Medicare populations calculated using the GLM model Conclusion Overall uUTI-related HRU and costs in the US were low during index episodes and follow-up. However, females with uUTI prescribed IA/SO ABs were more likely to incur higher HRU and costs than those prescribed AP&OP ABs, suggesting an unmet need for training to optimize uUTI prescribing per US guidelines. Disclosures Madison T. Preib, MPH, STATinMED Research (Employee, Former employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Xiaoxi Sun, MA, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Christopher Adams, MPH, STATinMED Research (Employee, Employee of STATinMED Research, which received funding from GlaxoSmithKline plc. to conduct this study) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background In 2016, the World Health Organization estimated the global incidence of gonorrhea (GC) to be 86.9 million, and the reported incidence of GC in 2017 was 145.8 cases per 100,000 females and 212.8 cases per 100,000 males in the US. GC therefore represents a significant global healthcare burden; as the infection can be recurrent, overall costs can accumulate. We undertook a systematic literature review (SLR) to examine the economic burden of illness for GC in key countries. Methods Systematic searches were conducted in MEDLINE, EMBASE, and Cochrane databases to identify English-language articles published from January 1, 2009–December 1, 2019 reporting data on the economic burden of uncomplicated urogenital GC (uuGC) in the US, the UK, Germany, Japan and China. The SLR was conducted in accordance with Preferred Reporting Items for Systematic Reviews and Meta-Analyses guidelines (2009). Articles were evaluated for eligibility using population, intervention, comparison, outcome, study design and time period criteria (Table). Dual-independent screening was used at both the abstract and full-text levels; data were captured by a single reviewer with validation by a second reviewer. Table. PICOS-T Study Selection Criteria Results The SLR identified 27 eligible articles (Figure), of which 17 studies (16 US, 1 UK) reported the economic burden of uuGC. The studies primarily reported cost data, with a subset reporting limited resource use. Lifetime costs for uuGC, when elaborated upon, considered the potential for pelvic inflammatory disease among women, and epididymitis in men, as well as lifetime medical costs associated with human immunodeficiency virus. Among the 16 studies reporting costs, the total estimated lifetime cost of uuGC in the US reached as high as $162.1 million. Costs varied vastly based on sex, with one study reporting lifetime estimates up to $163,433 for men but $7,534,692 for women in 2005. Nine studies described costs per patient/infection and found average costs ranging from $26.92–$438.46, though most fell in the range of $79–$354. Figure. PRISMA flow diagram of study inclusion and exclusion Conclusion We identified a large body of evidence detailing the economic burden of GC. The cost burden varied by sex and was higher for females. However, the vast majority of the evidence came from the US, highlighting the need for more global research. Disclosures Amber Martin, BS, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Monica Turner, MPH, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Emma Schiller, BA, Evidera (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Background E. coli is the predominant uropathogen isolated in uncomplicated urinary tract infections (UTI). Surveillance data suggest increasing antimicrobial resistance (AMR), although recent data from the outpatient setting are limited. Treatment is typically empiric and should be guided by local resistance rates; however, this is challenging in the absence of routine culture and assessment of regional AMR. We characterized AMR trends for E. coli isolated from females with outpatient UTI in the US, from 2011 to 2019. Methods A retrospective multicenter cohort study of antimicrobial susceptibility using data from the BD Insights Research Database (Franklin Lakes, NJ) was conducted. The first E. coli urine culture isolates representing each distinct susceptibility pattern within 30 days of index urine from 2011–2019 were included from females ≥ 12 years old. E. coli isolates were identified as not-susceptible (NS) if intermediate or resistant to trimethoprim-sulfamethoxazole (TMP-SMX NS), fluoroquinolone (FQ NS), nitrofurantoin (NFT NS), ESBL+ (by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime), and multi-drug resistant (MDR), defined as NS to ≥ 2 or ≥ 3 of FQ, TMP-SMX, NFT or ESBL+. Descriptive analyses characterized AMR (%) over time and generalized estimating equations were used to statistically assess AMR trends over time. Results A total of 1,513,882 E. coli isolates were tested at 106 to 295 US centers between 2011 and 2019. Over the study period, AMR remained persistently high (> 20%) for FQ and TMP-SMX and increased for the MDR (≥ 3 drugs) phenotype (from 3.1% to 4.0%) (Table). Prevalence of the ESBL+ phenotype increased year-on-year (from 4.1% to 7.3%). Modeling confirmed a significant increasing trend for the ESBL+ (7.7%/year) and MDR (≥ 3 drugs) phenotypes (2.7%/year) (P< 0.001), with decreasing or no trend change for NFT NS and other AMR phenotypes (Table). Table. Descriptive Statistics and Model-estimated Annual Change of AMR (count and % not-susceptible out of isolates tested) in E. coli among US Females (≥12 years of age) with Outpatient UTI Conclusion Characterization of AMR trends for E. coli over the last decade, in outpatient E. coli isolates in US females, shows persistently high AMR to FQ and TMP-SMX, and increasing AMR trends for the ESBL+ and MDR (≥ 3 drugs) phenotypes. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Gang Ye, PhD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Background Urinary tract infections (UTIs) are the most common bacterial infection requiring medical care. Despite Infectious Diseases Society of America (IDSA) 2011 guidelines on antimicrobial agent selection and duration of therapy for uncomplicated UTI (uUTI), prescribing practices vary. Few studies have used real-world data (RWD) to evaluate inappropriate and suboptimal antibiotic use among patients treated for uUTI. We examined the prevalence of potentially inappropriate and suboptimal use of antibiotics among females with uUTI. Methods This retrospective cohort study examined the first-line use of antibiotics in females (age ≥ 12 years) with diagnosed uUTI in the US, identified using RWD from IBM MarketScan (commercial and Medicare claims) Jan 1, 2013–Dec 31, 2017. Index date was the date of uUTI diagnosis. Patients were included based on criteria in Table 1 and assigned to one of two groups: appropriate and optimal; or inappropriate or suboptimal antibiotic use. As uUTI is often treated empirically, appropriate use was defined based on IDSA 2011 guidelines on drug class, dose and therapy duration; antibiotic use was considered suboptimal if there was evidence of treatment failure (Table 2). Table 1. Key inclusion and exclusion criteria Results In total, 557,669 patients with uUTI were included in the study; see Table 3 for baseline characteristics. Overall, 88.7% had inappropriate or suboptimal antibiotic use (Table 4). Of these, 86.1% had inappropriate use only, 2.1% had suboptimal use only, and 11.9% had both. Inappropriate drug class assignment was observed in 53.4% of patients with inappropriate use, 83.7% of whom were administered fluoroquinolones (a second-line agent) as first-line therapy. Among patients with inappropriate therapy duration: most given trimethoprim/sulfamethoxazole received 5- (27.2%), 7- (42.1%) or 10- (27.8%) days’ supply rather than the recommended 3 days; the majority given nitrofurantoin were provided a 7- (80.5%) or 10- (13.4%) day supply rather than the recommended 5 days; and 46.2% given fosfomycin received 3-days’ supply instead of the recommended 1 day. Table 3. Baseline characteristics Table 4. Patient disposition Conclusion In the treatment of uUTI, the prevalence of inappropriate and/or suboptimal antibiotic use is very high which may have subsequent implications for patient health outcomes. Disclosures Yuexi Wang, M.Econ, GlaxoSmithKline plc. (Other Financial or Material Support, Funding)STATinMED Research (Employee) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder) Lin Xie, MS, MA, GlaxoSmithKline plc. (Other Financial or Material Support, Funding)STATinMED Research (Employee) Mamta Jaiswal, PhD, GlaxoSmithKline plc. (Other Financial or Material Support, Funding)STATinMED Research (Employee) Xiaoxi Sun, MA, GlaxoSmithKline plc. (Other Financial or Material Support, Funding)STATinMED Research (Employee) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder)

Objectives Active-comparator, non-inferiority study designs are used in uncomplicated urinary tract infection (uUTI) to establish the efficacy of a new antibacterial, given the availability of effective antibiotics. Here we estimated the treatment effect of a planned antimicrobial comparator (nitrofurantoin) from historical trial data to properly design an upcoming non-inferiority trial in uUTI. Methods A systematic literature review and meta-analysis was conducted in compliance with the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines, which incorporate recommendations for standardised data quality assessment, reporting of results, risk of bias assessment and sensitivity analyses. To account for interstudy variability, a weighted, non-iterative, random-effects model was fit using R software to obtain estimates of the microbiological response rate and corresponding 95% confidence interval (CI) for nitrofurantoin and placebo treatment. Interstudy heterogeneity was assessed with Cochran's χ2 test for interstudy heterogeneity; I2 statistic and P-values were computed and included in the forest plot of the meta-analysis. Results Twelve unique studies met the final eligibility criteria for meta-analysis inclusion; three trials assessed placebo efficacy, eight trials assessed nitrofurantoin efficacy, and one study assessed both nitrofurantoin and placebo efficacy in uUTI. The overall microbiological response (95% CI) was 0.766 (0.665–0.867) for nitrofurantoin and 0.342 (0.288–0.397) for placebo. Conclusion The corresponding treatment effect estimate for nitrofurantoin was 26.8%, which supports a conservative non-inferiority margin of 12.5% and is consistent with the recently published draft FDA guidance. The findings from this systematic review and meta-analysis may inform future antibacterial trials by providing non-inferiority margin justification.

Background An estimated 12% of women experience ≥ 1 episode of urinary tract infection (UTI) annually. Incidence is bimodal, with peaks occurring in young, sexually active women (18–24 years) and in post-menopausal women. Previous studies suggest the prevalence of antimicrobial resistance (AMR) in UTI is rising; however recent AMR data for community-acquired UTI are lacking. We estimated the prevalence of AMR among US females with outpatient UTI in 2011–2019, stratified by age. Methods A retrospective, multicenter, cohort study of AMR among non-duplicate urine isolates in US females (≥ 12 years of age) from 296 institutions from 2011–2019 (BD Insights Research Database, Franklin Lakes, NJ). Phenotypes examined for Enterobacterales (ENT) were: extended spectrum β-lactamase positive (ESBL+; determined by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime); nitrofurantoin (NFT) not-susceptible (NS); fluoroquinolone (FQ) NS; trimethoprim-sulfamethoxazole (TMP-SMX) NS; and NS to ≥ 2 or ≥ 3 drug classes (including ESBL+). Gram-positive phenotypes were, methicillin resistant S. aureus and S. saprophyticus and vancomycin-resistant Enterococcus. Isolates were stratified by patient age (≥ 12 to < 18, ≥ 18 to < 55, ≥ 55 to < 65, ≥ 65 to < 75, ≥ 75 years). Chi-square tests were used to evaluate AMR difference between groups. Results In total, urine isolates were collected from 106 to 296 (2011–2019) US sites. Overall, the prevalence of antimicrobial NS increased with age for all E. coli phenotypes (all P< 0.001; Table 1), and for non-E. coli ENT (all P< 0.001), except NFT NS, which decreased from 70.6% to 59.7% (P=0.002; Table 2). The greatest difference between age groups in prevalence of resistance was observed for FQ NS E.coli: 5.8% (≥ 12 to < 18 years) vs 34.5% (≥ 75 years). For the multi-drug resistant E. coli phenotypes, resistance increased with age, ranging from 4.8–22.4% and 0.9–6.5% for ≥ 2 and ≥ 3 drug NS, respectively. Overall, the prevalence of resistance for Gram-positive phenotypes increased with age (all P< 0.001; Table 3). Table 1. Prevalence of antimicrobial resistance among E. coli isolates in US females with outpatient UTI by age group. Table 2. Prevalence of antimicrobial resistance among non-E. coli ENT isolates in US females with outpatient UTI by age group. Table 3. Prevalence of antimicrobial resistance among Gram-positive isolates in US females with outpatient UTI by age group. Conclusion The prevalence of AMR in E. coli and non-E. coli ENT increased with age among US females presenting for care in the outpatient setting overall. A similar trend increase by age is also seen in Gram-positive isolates. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Gang Ye, PhD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Background The 2019 CDC Threats Report lists extended spectrum β-lactamase (ESBL) producing Enterobacterales as a serious health threat. While the clinical epidemiology of uncomplicated urinary tract infection (uUTI) has remained stable, there has been a notable increase in antimicrobial resistance (AMR) among community-acquired uUTIs. Urine cultures are seldom ordered for uUTI as treatment is often empiric; local surveillance data may therefore be lacking. The study objective was to determine the prevalence and geographic distribution of AMR in urine E. coli isolates from females in the US outpatient setting. Methods A retrospective cross-sectional study of E. coli ambulatory urine isolates identified from females (≥ 12 years of age) at 296 facilities, with ≥ 1 quarter of data in 2019 (BD Insights Research Database, Franklin Lakes, NJ). Initial isolates representing each distinct susceptibility pattern within 30 days of index urine were included. E. coli isolates were identified as not-susceptible (NS) if intermediate/resistant to trimethoprim-sulfamethoxazole (TMP-SMX), fluoroquinolone (FQ), nitrofurantoin (NFT), ESBL+ (by commercial panels or intermediate/resistant to ceftriaxone, cefotaxime, ceftazidime or cefepime), and multi-drug resistant, defined as NS to ≥ 2 or ≥ 3 of FQ, TMP-SMX, NFT or ESBL+. Logistic regression models were used to evaluate resistance prevalence and variation across US census regions. Results Of 267,524 non-duplicate E. coli isolates evaluated, 25.1% (67,189) were TMP-SMX NS, 20.3% (54,359) were FQ NS, 7.3% (19,576) were ESBL+, 3.5% (9,453) were NFT NS, 14.0% (37,328) were NS to ≥ 2 drugs and 4.0% (10,814) were NS to ≥ 3 drugs. For all phenotypes, there was significant variation in resistance across census regions (all P< 0.001) with the highest in the East South Central region and lowest in the New England region of the US (Table). The figure shows regional prevalence of ESBL+ E. coli in 2019. Table. Antimicrobial resistance data from 30-day non-duplicate urine E. coli isolates in females ≥12 years old in 2019, by US census region. Figure. Heat map of the overall US geographic distribution of ESBL+ E. coli (30-day non-duplicate urine isolates) from females across 296 acute care facilities in 2019. Conclusion The 2019 prevalence of AMR in non-duplicate ambulatory E. coli urine isolates was notable: TMP-SMX NS and FQ NS were > 20%. In addition, there were significant regional differences in resistance, with the highest in the East South Central region of the US, for all NS phenotypes. These analyses inform, and may optimize, empiric treatment of uUTI and patient outcomes. Disclosures Vikas Gupta, PharmD, BCPS, Becton, Dickinson and Company (Employee, Shareholder)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Aruni Mulgirigama, MBBS, GlaxoSmithKline plc. (Employee, Shareholder) Ashish V. Joshi, PhD, GlaxoSmithKline plc. (Employee, Shareholder) Nicole Scangarella-Oman, MS, GlaxoSmithKline plc. (Employee, Shareholder) Kalvin Yu, MD, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Anthony Boyles, MSc, Becton, Dickinson and Company (Employee)GlaxoSmithKline plc. (Other Financial or Material Support, Funding) Fanny S. Mitrani-Gold, MPH, GlaxoSmithKline plc. (Employee, Shareholder)

Noninferiority trial design and analyses are commonly used to establish the effectiveness of a new antimicrobial drug for treatment of serious infections such as complicated urinary tract infection (cUTI). A systematic review and meta-analysis were conducted to estimate the treatment effects of three potential active comparator drugs for the design of a noninferiority trial. The systematic review identified no placebo trials of cUTI, four clinical trials of cUTI with uncomplicated urinary tract infection as a proxy for placebo, and nine trials with reports of treatment effect estimates for doripenem, levofloxacin, or imipenem-cilastatin. In the meta-analysis, the primary efficacy endpoint of interest was the microbiological eradication rate at the test-of-cure visit in the microbiological intent-to-treat population. The estimated eradication rates and corresponding 95% confidence intervals (CI) were 31.8% (26.5% to 37.2%) for placebo, 81% (77.7% to 84.2%) for doripenem, 79% (75.9% to 82.2%) for levofloxacin, and 80.5% (71.9% to 89.1%) for imipenem-cilastatin. The treatment effect estimates were 40.5% for doripenem, 38.7% for levofloxacin, 34.7% for imipenem-cilastatin, and 40.8% overall. These treatment effect estimates can be used to inform the design and analysis of future noninferiority trials in cUTI study populations.

A systematic literature review and meta-analysis were conducted to estimate the antibacterial treatment effect for linezolid and ceftaroline to inform on the design of acute bacterial skin and skin structure infection (ABSSSI) noninferiority trials. The primary endpoints included an early clinical treatment response (ECTR) defined as cessation of lesion spread at 48 to 72 h postrandomization and the test-of-cure (TOC) response defined as total resolution of the infection at 7 to 14 days posttreatment. The systematic review identified no placebo-controlled trials in ABSSSI, 4 placebo-controlled trials in uncomplicated skin and soft tissue infection as a proxy for placebo in ABSSSI, 12 linezolid trials in ABSSSI, 3 ceftaroline trials in ABSSSI, and 2 trials for nonantibacterial treatment. The ECTR rates at 48 to 72 h and corresponding 95% confidence intervals (CI) were 78.7% (95% CI, 61.1 to 96.3%) for linezolid, 74.0% (95% CI, 69.7 to 78.3%) for ceftaroline, and 59.0% (95% CI, 52.8 to 65.3%) for nonantibacterial treatment. The early clinical treatment effect could not be estimated, given no available placebo or proxy for placebo data for this endpoint. Clinical, methodological, and statistical heterogeneity influenced the selection of trials for the meta-analysis of the TOC treatment effect estimation. The pooled estimates of the TOC treatment response were 31.0% (95% CI, 6.2 to 55.9%) for the proxy for placebo, 88.1% (95% CI, 81.0 to 95.1%) for linezolid, and 86.1% (95% CI, 83.7 to 88.6%) for ceftaroline. The TOC clinical treatment effect estimation was 25.1% for linezolid and 27.8% for ceftaroline. The antibacterial treatment effect estimation at TOC will inform on the design and analysis of future noninferiority ABSSSI clinical trials.

Summary Objective A systematic review of the literature was conducted to summarize the descriptive and molecular epidemiology of human cases and surveillance reports with New Delhi metallo-β-lactamase type 1 (NDM-1)-producing bacteria reported worldwide from January 2008 through July 6, 2011. Methods A comprehensive literature review was conducted to identify publications of NDM-1-producing bacteria. Studies were divided into two broad categories of (1) case series and case reports of NDM-1-producing bacteria, or (2) active surveillance and environmental surveillance studies of NDM-1-producing bacteria. Results Sixty cases with NDM-1-producing bacteria were reported in the 3.5-year interval since the index case detection. The majority of reported cases represented colonization without evidence of infection ( n =39, 65%); urine was the most common specimen source for cases with infection (41.7%) and colonization (33.3%). Seventeen cases (28.3%) had NDM-1-producing bacteria at more than one body site. Klebsiella pneumoniae and Escherichia coli were the most frequent bacteria detected, and the multilocus sequence type data from 34 E. coli and K. pneumoniae clinical isolates provided an incomplete, yet heterogeneous global distribution of NDM-1-producing bacteria. The majority of cases (63.3%) had exposure to the Indian subcontinent of south central Asia, and laboratory surveillance systems, as well as an environmental survey from India, suggest a presence of environmental reservoirs for potential human infection and colonization with NDM-1-producing bacteria. Conclusions The majority of case reports with NDM-1-producing bacteria had presumed colonization, not infection, with one or more bacteria. The available human case reports and surveillance data suggest a global distribution of NDM-1-producing Enterobacteriaceae and non- Enterobacteriaceae .

Published data on the epidemiology of idiopathic thrombocytopenic purpura (ITP) among adults are very limited. We conducted a study of ITP incidence using the General Practice Research Database in the United Kingdom. From 1992 to 2005, there were 840 cases of ITP among adults considering 21 749 623 person-years (PYs) of follow-up, for a crude incidence of 3.9 per 100 000 PYs [95% confidence interval (CI): 3.6, 4.1]. The incidence was higher among women [4.5 per 100 000 PYs (95% CI: 4.2, 4.9)] than men [3.2 per 100 000 PYs (95% CI: 2.8, 3.5)]. Among both women and men, incidence was higher at older ages and in later study years. In a systematic review of previously published literature, incidence of ITP among adults ranged from 1.6 to 2.68 per 100 000 persons per year; prevalence ranged from 9.5 to 23.6 per 100 000 persons. In order to improve the understanding of the disease burden of ITP, future studies should include a clearly defined definition of ITP and focus on well-described source populations that are geographically and ethnically diverse.