bluuebunny/crossref_metadata_2025_split huggingface dataset:
2831. Efficacy and Safety of Gepotidacin for Uncomplicated Urinary Tract Infection: Pooled Subgroup Analyses of the EAGLE-2 and EAGLE-3 Randomized Phase 3 Trials
Authors: Hooton Thomas M , Perry Caroline R , Janmohamed Salim , Sheets Amanda , Dennison Jeremy , Millns Helen , Jarvis Emily , Huang Chun 
Published: November 2023

Abstract

Background
Two large Phase 3 trials showed that gepotidacin, a first-in-class oral triazaacenaphthylene bactericidal antibiotic, was efficacious in treating uncomplicated urinary tract infection (uUTI) in females and had an acceptable safety profile consistent with prior gepotidacin trials. We now present a pooled analysis of the EAGLE-2 and EAGLE-3 trials to evaluate gepotidacin efficacy and safety in patient subgroups.

Methods
Data were pooled from EAGLE-2 and EAGLE-3, near identical global, Phase 3, randomized, double-blind, double-dummy, active-controlled non-inferiority trials comparing oral gepotidacin (1500mg) to nitrofurantoin (100mg), both twice daily for 5 days. Females aged ≥ 12 years with ≥ 2 uUTI symptoms were eligible. Therapeutic success (combined clinical and microbiological success) was determined at the test-of-cure visit (Day 10–13) for patient subgroups – age, geographic region, history of recurrent uUTI, diabetes, and renal function. Efficacy subgroup analyses were conducted in the pooled microbiological intent-to-treat population of patients with baseline uropathogens (≥ 105 CFU/mL) susceptible to nitrofurantoin (micro-ITT NTF-S) and were adjusted for study. Pooled adverse event (AE) data for the overall population are presented.

Results
Both studies stopped early for efficacy (per independent data monitoring committee review). Among 1201 patients in the pooled micro-ITT NTF-S population, mean age was 51.5 years; 54% were aged &gt; 50 years (Table 1). Across subgroups, differences in therapeutic success numerically favored gepotidacin vs nitrofurantoin (Table 2). Treatment differences were higher for &gt; 50 years vs other age groups and for mild renal impairment vs normal renal function, and were similar within other subgroups. AEs were reported in 35% (gepotidacin) and 23% (nitrofurantoin) of patients (Table 3); most were mild to moderate and gastrointestinal in nature. There were few serious AEs.

Conclusion
Gepotidacin generally demonstrated consistent therapeutic efficacy in patient subgroups, including patients aged &gt; 50 years and those with a history of recurrent uUTI (subgroups at higher risk of treatment failure). There were no new or concerning safety signals. Gepotidacin has potential as a novel oral treatment for uUTI in key patient subgroups.

Disclosures
Thomas M. Hooton, MD, GSK: Advisor/Consultant Caroline R. Perry, PhD, GSK: Employee and shareholder Salim Janmohamed, MD, GSK: Employee and shareholder Amanda Sheets, PhD, GSK: Employee and shareholder Jeremy Dennison, MD, GSK: Employee and shareholder Helen Millns, PhD, GSK: Employee and shareholder Emily Jarvis, MSc, GSK: Employee and shareholder Chun Huang, PhD, GSK: Employee and shareholder
2833. Multi-drug resistance of Escherichia coli from outpatient uncomplicated urinary tract infections in a large U.S. integrated health care organization
Authors: Ku Jennifer H , Bruxvoort Katia J , Salas Suzanne B , Varley Cara D , Casey Joan A , Raphael Eva , Robinson Sarah , Nachman Keeve , Lewin Bruno , Contreras Richard , Wei Rong , Pomichowski Magdalena , Takhar Harpreet , Tartof Sara Y 
Published: November 2023

Abstract

Background
Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multi-drug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision-making.

Methods
We evaluated UPEC resistance over time and by care setting (in-person vs. virtual), in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021.

Results
We included 174,185 individuals who had ≥1 UPEC uUTI (233,974 isolates), who were 92% female, and 46% Hispanic with a mean age 52 years (standard deviation 20). Overall, UPEC MDR decreased during the study period (13 to 12%) (Figure 1) both in virtual and in-person settings (p-for trend &lt; 0.001). Resistance to penicillins overall (29%), co-resistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving penicillins and TMP-SMX plus ≥1 antibiotic class were common (10%) (Figure 2). Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time, and by care setting.
Figure 2. Antibiotic resistance patterns of outpatient uncomplicated Escherichia coli urinary tract events, Kaiser Permanente Southern California, 2016 – 2021. Abbreviations: PNC = penicillin; FLQ = fluoroquinolone; TMP-SMX = sulfamethoxazole and trimethoprim; AGS = aminoglycoside; NFT = nitrofurantoin; CSP = cephalosporin

Conclusion
We observed a slight decrease in both class-specific AMR and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX, and consistent over time and by care setting. Virtual healthcare may expand access to UTI care without increased risk for MDR and the need for setting-specific antibiograms.

Disclosures
Jennifer H. Ku, PhD MPH, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Sara Y. Tartof, PhD MPH, Genentech: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Grant/Research Support|SPERO: Grant/Research Support
2836. Prostate Abscess due to Staphylococcus aureus: a Retrospective Case Series
Authors: Pellis Zachary , Mudroch Steven , Spivack Stephanie 
Published: November 2023

Abstract

Background
Most cases of prostate abscess are due to gram-negative enteric bacteria, but there are increasing reports of Staphylococcus aureus as a causative pathogen. Due to being an uncommon diagnosis, there are no current guidelines for the evaluation and treatment of S. aureus prostate abscesses. We examined the epidemiology and management of prostatic abscess due to S. aureus at an academic, urban tertiary center.

Methods
In this retrospective analysis, we identified patients with diagnosis of prostate abscess and concomitant culture with S. aureus who were aged 18 years or older and hospitalized at Temple University Hospital between 2016 and 2022. Cases were identified if they had both (1) a diagnosis code consistent with prostate abscess; and (2) positive blood, urine, or abscess cultures with S. aureus. Each case was reviewed to verify clinical or imaging criteria for diagnosis. Data regarding risk factors, interventions, and outcomes were compiled in REDCap, a de-identified electronic database for data management.

Results
We identified 18 patients who met inclusion criteria, with median [IQR] age of 50 years [40-70]. Computed tomography was used in all cases for identifying an abscess. The most common risk factors were intravenous drug use (IVDU) 55.6% [10/18] and diabetes 50% [9/18]. Culture positivity was 100% [6/6] for abscess fluid, 61.1% [11/18] for urine, and 56.3% [9/16] for blood. Of these, methicillin resistance was detected in 72.2% [13/18] of cases. Computed tomography was used in all cases for identifying an abscess. 61.1% [11/18] of patients underwent procedural interventions for treatment. Infectious Diseases consultation resulted in a change in management in 92.8% [13/14] of cases, with a median length of antibiotic administration of 42 days. 66.7% [6/9] of the bacteremic patients had additional infectious complications such as endocarditis or osteomyelitis.

Conclusion
Prostate abscess due to S. aureus should be considered in patients presenting with lower urinary tract symptoms and a history of injection drug use or diabetes. Evaluation should include imaging and cultures, particularly from blood. Treatment involves prolonged antibiotics and urology consultation for consideration of procedural intervention.

Disclosures
All Authors: No reported disclosures
172. Impact of a quality improvement re-training program on the blood culture volume, yield and contamination rates; experience from South India
Authors: Rabbani Amaanulla Kaamil Zubair , Ananthanarayanan Rajalakshmi , Asok Geetha Karthik , Rahim Mulla Rukhsar Abdur , Muhammed Niyas Vettakkara Kandy , Nair Ashalatha , Jomes Jeffrey , Hussain Febeena 
Published: November 2023

Abstract

Background
Blood cultures help to detect causative agents in bacteremia and are important for targeted therapy. Adequate blood culture volume is considered as 8-10ml in each bottle and at least 2 aerobic and 2 anaerobic blood culture bottles are recommended. Inadequate blood culture fills are common and may affect yield.
Figure 1

Methods
The study was done in our healthcare facility-KIMSHEALTH, Trivandrum, India. Pre-intervention period was between May 2021 and June 2021; post-intervention was between May 2022 and June 2022. The intervention was through plan/do/study/act (PDSA) cycles and included multiple training sessions to the phlebotomy team regarding adequate fill volume which is 8-10 ml in each blood culture bottle. Training for maintaining asepsis during collection was reinforced. All blood culture samples received in the hospital microbiology laboratory during the above period were included in this study and compared between the pre-intervention and post-intervention period. Pediatric blood culture samples were excluded.

Results
Blood culture samples studied during pre and post intervention period were 1428 and 1716 respectively. In the pre-intervention phase adequate fill volume was noted in 30.81% bottles (figure 1), while in the post intervention adequate fill volume was noted in 68.06% bottles (p &lt; 0.01). Blood culture contamination rate was 3.01% in the pre-intervention period which improved to 2% in the post-intervention period and the difference was significant (p&lt; 0.01). Blood culture yield of a pathogenic organism did not show significant difference after the intervention (11.2% in pre-intervention group Vs 11.45% in post intervention group).

Conclusion
In this study, an improvement was noted in the blood culture fills by 38% and contamination rate reduced by 1%. Though there was no significant increase in blood culture yield with intervention, the reduction in contamination was noted which will reduce unnecessary antibiotic initiation.

Disclosures
All Authors: No reported disclosures
2846. Microbiological Characteristics of the Patients with Acute Pyelonephritis who experienced Urinary Tract Infections within prior to 1 year
Authors: Yoon Choseok , Kim Jeoungyeon , Jang Wooyoung , Go Ji Won , Kim Jinnam , Lee Yangsoon , Kim Bongyoung 
Published: November 2023

Abstract

Background
Approximately 15% of patients with acute pyelonephritis (APN) experience another urinary tract infection (UTI) within 1 year in South Korea. The purpose of this study is to examine the microbiological characteristics of patients with APN who experienced UTIs within prior to 1 year.

Methods
A retrospective cohort study was performed in a tertiary-care hospital in South Korea from July 2019 to December 2021. All female patients who were diagnosed with community acquired APN at admission were recruited. Patients who had prolonged hospitalization period due to medical problems that were not associated with APN treatment were excluded. We regarded recurrent group as the cases which have history of UTI within 1 year. Types of causative organism, major antibiotic resistance of E.coli isolated from patients' urine or blood, and the genetic characteristics of E.coli were compared between recurrent group and non-recurrent group.

Results
A total of 285 APN patients were finally included in this study, of which 41 (14.4%) were belong to recurrent group. E.coli was the most common causative pathogens in both groups, but the proportions of some pathogens, such as Klebsiella pneumonia (17.1 vs. 4.7%, P=0.007) and Pseudomonas aeruginosa (5.7 vs. 0.5%, P=0.014) were higher in the recurrent group than the non-recurrent group. There were no significant differences between the two groups in the proportions of antibiotic resistances to E.coli, such as amikacin (0 vs. 1.2%, P=0.597), cefotaxime (25.0 vs. 22.5%, P=0.788), and fluoroquinolone (20.8 vs. 28.9%, P=0.409), etc. The most prevalent β-lactamase and PMQR determinant were CTX-M-1G (44.4 vs 60.0%, P=0.308) and aac(6’)-lb-cr (50.0 vs 36.2%, P=0.303), respectively, and the predominant clone was ST131 (22.2 vs 17.8%, P=0.744) in both groups. However, there were no significant differences in the proportions of phylogenic groups, resistance genes, and virulence factors between the two groups.

Conclusion
E.coli was the most common causative pathogens in both groups, but the proportion of pathogens except E.coli was higher in the recurrent group than the non-recurrent group. There were no significant differences between the two groups in the proportions of antibiotic resistances to E.coli, phylogenic groups, resistance genes, and virulence factors.

Disclosures
All Authors: No reported disclosures
2848. Risk factors for recurrence of community-onset urinary tract infections caused by extended spectrum cephalosporin-resistant Enterobacterales
Authors: Zhang Helen L , Perez Reinaldo , Krishnan Jay , Lautenbach Ebbing , Anderson Deverick J 
Published: November 2023

Abstract

Background
Extended spectrum cephalosporin-resistant Enterobacterales (ESCR-E) are increasingly implicated in community-onset urinary tract infections (UTIs). In this study, we assessed risk factors for recurrence among patients with community-onset UTI caused by ESCR-E.

Methods
This retrospective cohort study included adult patients evaluated April 2018 – December 2021 in the Duke University Health System with community-onset ESCR-E UTI, defined as (1) ESCR-E in a urine culture obtained in an outpatient clinic, emergency department, or within 48 hours of hospital admission; (2) ≥10 leukocytes per high-power field on urine microscopy or urine dipstick positive for leukocyte esterase; and (3) new antibiotic administration or prescription. ESCR-E UTI recurrence was assessed 14 to 180 days after completion of antibiotic treatment for the index UTI. Patients were right censored at end of follow up period or upon death. Univariate Cox proportional hazards regression was performed to evaluate the relationships between candidate risk factors and time to recurrence.

Results
1428 patients were included; 207 (14.5%) experienced recurrence. In unadjusted analyses, risk factors for recurrent ESCR-E UTI included diabetes mellitus (hazard ratio [HR] = 1.4, 95% confidence interval [CI]: 1.1 to 1.9, p = 0.01), chronic renal insufficiency (HR = 1.6, 95% CI: 1.2 to 2.1, p &lt; 0.001), neurogenic bladder (HR = 2.1, 95% CI: 1.4 to 2.9, p &lt; 0.001), previous UTI diagnosis within one year (HR = 2.6, 95% CI: 1.9 to 3.5, p &lt; 0.001), fluoroquinolone non-susceptibility (HR = 1.6, 95% CI: 1.2 to 2.2, p = 0.004), and trimethoprim-sulfamethoxazole non-susceptibility (HR = 1.3, 95% CI: 1.0 to 1.8, p = 0.045). Patients with ESCR Klebsiella pneumoniae UTI had a 53% greater hazard of recurrence compared to patients with ESCR E. coli UTI (HR = 1.5, 95% CI: 1.1 to 2.1, p = 0.008).

Conclusion
ESCR-E UTI recurrence was common, and several clinical and microbiologic characteristics were associated with recurrence. Patients with these characteristics should receive particular consideration for aggressive UTI risk factor modification and other non-antibiotic prevention strategies. Future studies should evaluate strategies to reduce the risk of recurrence among patients with ESCR-E UTI.

Disclosures
All Authors: No reported disclosures
174. Impact of Ceftaroline Duration after Bacteremia Clearance When Used in Combination Therapy for Persistent or High-grade MRSA Bacteremia
Authors: Cabanilla M Gabriela , Atallah Liana , Bernauer Michael , Briski Matthew , Koury Jason , Thompson Cecilia , Rodriguez Chelsea , Jakeman Bernadette , Byrd Thomas 
Published: November 2023

Abstract

Background
Methicillin resistant Staphylococcus aureus (MRSA) bacteremia is a clinically relevant syndrome with high mortality. Combination therapy with beta-lactam antibiotics has been employed in persistent MRSA bacteremia with reported clinical success. Ceftaroline is a beta-lactam antibiotic with activity against MRSA, which has been commonly used in combination therapy for this indication. However, adequate ceftaroline duration after bacteremia clearance continues to be elucidated. Thus, we aimed to evaluate clinical outcomes of patients receiving short vs. long duration of ceftaroline after persistent or high-grade bacteremia clearance.

Methods
This was a single-center, retrospective cohort study conducted from January 1, 2014, to June 30, 2021. Patients were included if ≥18 years of age, with high grade or persistent MRSA bacteremia, who received combination therapy with ceftaroline. The primary outcome was 30-day mortality. Secondary outcomes included hospital length of stay, time to bacteremia clearance, antibiotic-related adverse events and microbiological relapse.

Results
A total of 32 patients were included (mean age: 51.5 years; 71.9% white; 61.3% male). 96.9% had high-grade MRSA bacteremia and 68.8% had persistent bacteremia. The most common bacteremia source was bone and joint infections (28.1%). 56.3% of patients received ceftaroline in combination with vancomycin; mean duration was 8 days. Multivariable analysis showed increasing the duration of combination therapy after bacteremia clearance was not associated with a lower risk of 30-day mortality after controlling for Charlson comorbidity index and Pitt bacteremia scores (OR 0.75, 95% CI 0.94-2.45; p=0.07). Similarly, no association was observed with microbiological relapse (OR 1.03, 95% CI 0.92-1.16; p=0.73), antibiotic-related adverse event (OR 0.97, 95% CI 0.78-1.10; p=0.75), time to bacteremia clearance (p=0.88) or hospital length of stay (p=0.06).

Conclusion
Longer durations of ceftaroline in combination therapy after bacteremia clearance was not associated with lower rates of 30-day mortality, microbiological relapse, or higher rates of antibiotic-related adverse events. Larger studies are needed to determine the appropriate duration of combination therapy.

Disclosures
Cecilia Thompson, PhD, D(ABMM), MLS (ASCP), Roche Diagnostics: Honoraria
176. Impact of Rapid Blood Culture Identification Panel on Antibiotic Treatment and Clinical Outcomes in Bloodstream Infections, Particularly Those Associated with Multidrug-resistant Microorganisms
Authors: Yun Bae Ji , Bae Jiyeon , So Min-Kyung , Jung Choi Hee , Lee Miae 
Published: November 2023

Abstract

Background
The FilmArray Blood Culture Identification (BCID) panel (BioFire Diagnostics, USA) can detect 19 bacteria, five Candida spp., and three antimicrobial resistance determinants (mecA, vanA/B, and bla-KPC). This study evaluated the impact of BCID on the time to effective antibiotic administration and clinical outcomes in bloodstream infections, particularly carbapenem-resistant Enterobacterales (CRE), vancomycin-resistant enterococci (VRE) and carbapenem-resistant Acinetobacter baumannii (CRAB) bacteremia.

Methods
The clinical outcomes and time to effective antibiotic administration for bloodstream infections were retrospectively compared between patients who had undergone BCID testing and conventional culture method (control group). Further, we compared the 30-day mortality and time to effective antibiotic administration between BCID and conventional methods in CRE, CRAB, and VRE bacteremia.

Results
We compared 144 and 214 patients who had undergone BCID testing and the conventional culture method, respectively. The median time until the administration of effective antibiotics (3 h for both BCID and conventional culture, P = 0.789), appropriate antibiotics (BCID: 37 h vs. conventional culture: 44 h, P = 0.727), and 30-day mortality (BCID: 9.7% vs. conventional culture: 10.7%, P = 0.755) did not differ significantly between the groups. Multivariable analysis revealed that BCID was not associated with 30-day mortality after adjusting for Pitt bacteremia and Charlson comorbidity index (adjusted OR: 0.833, CI: 0.398–1.743) (Table 1).
BCID did not reduce the risk of 30-day mortality in any subgroup: patients with ICU stay, hematologic department admissions, hospital-acquired infections, gram-positive and gram-negative bacteremia. Time to effective antibiotic administration was significantly reduced on using BCID in patients with CRE and VRE bacteremia, while no difference was observed in patients with CRAB bacteremia (Table 2).

Conclusion
BCID did not improve the clinical outcomes of overall bloodstream infections. However, it contributed to the early administration of effective antibiotics in patients with CRE and VRE bacteremia. BCID may be useful in selected patients in whom infection with multidrug-resistant microorganism is suspected.

Disclosures
All Authors: No reported disclosures
177. Infectious Diseases Consultation Associated with Decreased Mortality in Gram-Negative Bacteremia
Authors: Bruning Rebecca , Runyon Kyler , Burgess Donna R , Cotner Sarah , Olney Katie B , VanHoose Jeremy , El Haddad Hanine , Burgess David 
Published: November 2023

Abstract

Background
Bloodstream infections (BSIs) are major causes of morbidity and mortality for which prior analyses and validated scoring tools have attempted to stratify risk. This study investigated institutional and epidemiologic predictors of mortality with Gram-negative BSIs to better identify targeted antimicrobial stewardship efforts to improve outcomes.

Methods
All patients with aerobic, monomicrobial, Gram-negative BSIs admitted and discharged from our academic medical institution between July 2022 and March 2023 were included. Data collected included patient demographics, microbiological data, clinical management, length of stay, ID consultation, and clinical outcomes (in-hospital or hospice mortality). Univariate and multivariable logistic regression models were performed to identify variables that were primary drivers for inpatient mortality.

Results
Overall, 259 patients (83.7% Caucasian, 49% male, mean age 53.7 yrs) were identified. The most common organisms were E. coli (37.8%), K. pneumoniae (11.2%), P. aeruginosa (10.0%), S. marcescens (8.5%), and E. cloacae (6.2%). The majority (65.3%) were community acquired infections with 41.7% in the ICU, and 46.7% received an infectious diseases consult. The overall mortality was 14.7% with the highest mortality due to P. aeruginosa (34.6%) followed by S. marcescens (27.3%), K. pneumoniae (13.8%), E. cloacae (12.5%), and E. coli (8.2%). Overall mortality was significantly associated with several parameters in a univariate analysis (Table 1). In multivariable regression analysis hospital-acquired infection (0=0.002), cancer (p=0.012), qPitt &gt; 2 (p&lt; 0.001), SBP&lt; 100 or vasopressor use at 72-96 hrs after positive blood culture (p=0.017) was associated with increased risk of mortality. The only parameter to reduce mortality within the multivariable regression analysis, by more than two-fold, was ID consultation (p=0.022).
Parameters Associated with Mortality in Univariate Analysis

Conclusion
The only factor found to significantly reduce mortality was formal ID consultation. ID consultation should be considered part of routine care for all patients with Gram-negative bacteremia.

Disclosures
Katie B. Olney, PharmD, BCIDP, The Society of Infectious Diseases Pharmacists (SIDP): Grant/Research Support