Extended-spectrum Beta-lactamase Research Articles

Contamination of retail market meat with extended-spectrum beta-lactamase genes in Vietnam.

The contamination of retail meat with antibiotic-resistant bacteria poses a substantial public health risk because of the potential spread of these bacteria within communities. The contamination of retail meat with extended-spectrum beta-lactamase (ESBL)-producing bacteria was investigated in four cities in Vietnam using real-time PCR, employing ESBL marker genes. This method provides a more comprehensive assessment of ESBL-producing bacterial contamination in meat samples than culture-based methods because it directly detects resistance genes from the extracted sample DNA. Retail meats in Vietnam were substantially contaminated with ESBL genes [54% (n=46) and 48% (n=49) of chicken and pork samples, respectively]. No significant differences in ESBL gene detection rates were observed between chicken and pork. The most frequently detected ESBL gene was blaTEM, followed by blaSHV, whereas blaCTX-M was found in only 4-8% of the samples. Ho Chi Minh City showed significantly higher contamination rates for both chicken and pork than those in other cities. ESBL-producing Escherichia coli strains were isolated from contaminated meat samples and genomically analyzed. All isolated strains carried blaCTX-M, with some harboring blaTEM, whereas blaSHV was not detected. Although IncFIB plasmids were prevalent among the ESBL-producing E. coli strains, the variability in resistance gene profiles suggested that the endemic spread of specific resistance gene-carrying plasmids was unlikely. Overall, these findings highlight the effectiveness of the ESBL gene detection method and the high levels of ESBL-producing E. coli in retail meat.

Detections of antimicrobial resistance phenotypes and extended-spectrum beta-lactamase (ESBL)- producing Salmonella spps and Escherichia coli O157:H7 in raw vegetables and fruits from open markets in Jimma town, Ethiopia and evaluation of hygiene and handling practices of vendors

ObjectivesDespite of the health benefits of consumption of fresh vegetables and fruits, this product could be associated with food-borne bacterial pathogens, including infections with antibiotic-resistant strains especially in developing countries due to limited in knowledge, and hygienic practices. This study was conducted to provide evidence data on the rates of Salmonella spp. and E. coli O157:H7 contamination, the antimicrobial resistance profile, and extended-spectrum β-lactamase (ESBL)-producing strains in fresh vegetables and fruits sold in open-air markets at Jimma town, southwest Ethiopia. In addition, this study provided data on the hygiene and handling practices of vendors, which can help as impute to improve food safety and safeguard public health. A total of 242 salad samples were collected from three different kebeles and examined for the presence of Salmonella spp. and E. coli O157:H7 in the microbiology laboratory of Jimma University by using conventional microbiological techniques.ResultsOut of 242 samples tested, 12.8% (31/242) were contaminated with Salmonella spp. and E. coli O157. Of these, Salmonella spp. was detected in 10.7% (26/242) of the tested samples, whereas Escherichia coli O157:H7 was found in 2.1% (5/242) of samples. Fifty-three-point-8% of Salmonella spp. were resistant to ampicillin, 42.3% to co-trimoxazole, 46.2% to tetracycline, and 26.9% resistance was observed against each of ceftriaxone and cefotaxime. 40% of E. coli O157:H7 isolates were resistant against ampicillin, amoxicillin-clavulanic acid, and co-trimoxazole. Only one isolate was resistant to ceftriaxone and cefotaxime, and no resistance was observed against ceftazidime, gentamicin, ciprofloxacin, chloramphenicol, and meropenem. Four Salmonella spp. and one E. coli O157:H7 isolate with a total of 5/31 (16.1%) isolates were confirmed as the ESBL producers. Multidrug resistance (MDR) was detected in 23.1% of Salmonella and 20.0% of E. coli O157:H7. Hygienic and handling practices of vendors were poor, which could contribute to contamination of vegetables and fruits in the area.ConclusionsContamination of fresh salad vegetables with pathogenic bacteria could be a food safety concern in the study area. Hence, this finding suggests the need for attention by the concerned bodies to prevent the emergence and transmission of food-borne pathogens and antimicrobial-resistant strains through these food items in the study area.

Prevalence of antimicrobial resistance phenotypes and genes in stable fly- and manure-derived bacterial isolates from clinically relevant taxa in dairy settings.

This study aimed to characterize and compare the antimicrobial resistance (AMR) profiles of clinically relevant bacterial taxa isolated from biting stable flies (Stomoxys spp.) and bovine manure samples collected at a dairy research facility over the course of an entire fly breeding season. The presence of extended-spectrum beta-lactamase (ESBL) and other antimicrobial resistance genes (ARGs) was also examined. A total of 606 fly- and 180 manure-derived strains were tested via disk diffusion for susceptibility to commonly administered antibiotics used in veterinary and human medicine. A small percentage of Enterobacterales exhibited resistance to the tested antimicrobials, including ceftiofur and other beta-lactam antibiotics. Extended spectrum beta-lactamase genes (TEM, CTX, OXA, CMY) were detected by PCR amplification in ceftiofur-resistant Escherichia coli, Klebsiella and Enterobacter spp. isolates. We additionally identified pirlimycin-resistant Staphylococcus and Mammaliicoccus spp. isolates encoding lnuA, a lincosamide resistance gene found primarily on small mobilizable plasmids. These findings highlight the significance of stable flies in the carriage of antimicrobial-resistant bacterial strains and plasmid-associated ARGs on dairy farms.

P-1343. Extended Spectrum Beta Lactamases (ESBL) and New Delhi Metallo Protein (NDM) genes co-occurrence in Phenotypic ESBL Enterobacteriaceae (ESBL-E) isolates causing community-acquired pyelonephritis

Abstract Background Multidrug resistance Enterobacteriaceae causing community-acquired pyelonephritis is an emerging threat; most isolates are EBSL, as per Indian data. After the results of the MERINO trial, most guidelines favors Carbapenem for treating community-acquired pyelonephritis. Overuse of carbapenem may lead to Carbapenem resistance Enterobacteriaceae (CRE) in the community. We analyzed the ESBL and CRE genes in the clinically significant urinary isolates with phenotypic ESBL -E from patients with community-acquired pyelonephritis.Table 1Demographic characteristics of patients with community-acquired acute pyelonephritis caused by phenotypic ESBL -E. Methods Patients with a diagnosis of community-acquired acute pyelonephritis with age ≥ 18 years and urine culture showing the growth of Enterobacteriaceae with phenotypic ESBL-E are included in the study. If urine culture grew more than one organism in Enterobacteriaceae, other GNBs were excluded. The phenotypic ESBL detection was based on resistance to a third-generation cephalosporin (Cefotaxime, Cefpodoxime, Ceftazidime) and a monobactam (Aztreonam). These positive isolates were further processed using the combination disk method. A ≥5mm increase in zone diameter for either antimicrobial agent tested in combination with clavulanate vs the zone diameter of the agent when tested alone was considered ESBL (Clinical and Laboratory Standards Institute (CLSI) Performance standards for antimicrobial susceptibility tests). Simultaneously, multiplexed Real-time PCR (TRUPCR® UTI AST Panel Kit, Europe) was done to detect ESBL genes (CTX-M, TEM, SHV) and CRE genes (OXA-48, KPC, NDM, VIM, IMP) in these isolates.Table 2:Detection of NDM genes with ESBL genes in patients with community-acquired acute pyelonephritis caused by phenotypic ESBL -E. Results A total of 38 isolates with phenotypic ESBL in patients diagnosed with community-acquired pyelonephritis were processed for RT-PCR, and 30 were detected with ESBL and CRE genes. The demographic and clinical characteristics are shown in Table 1. The most common ESBL gene was CTX-M 29 (.96.7%) followed by TEM 25 (83.3%). Multiple ESBL genes were detected in 24(80%) isolates. Among CRE genes, the NDM genes were detected in 15 (50%) isolates with other ESBL genes (Table 2). Conclusion The presence of CRE genes in phenotypic ESBL -E in community-acquired acute pyelonephritis could be due to the injudicious use of carbapenem. This may imply that CRE will be spread in the community in the future, making it difficult to manage this infection. Disclosures All Authors: No reported disclosures

P-1454. Characterizing the Prevalence of Recurrent Antimicrobial Resistant Infections in an Urban County

Abstract Background Individuals treated for antimicrobial resistant organism (AMRO) infections are exposed to broader antibiotics, which can contribute to an increased likelihood of future resistant infections. Given that community transmission and AMRO recurrence remains underexplored, we conducted spatiotemporal analyses of recurrent AMRO infections in an urban county. Figure 1 Map of spatiotemporal hotspots and recurrent infection counts per 1,000 population (CP1K) for five patterns of antimicrobial resistance at a census block group level. Methods We mapped the spatial prevalence of recurrent AMRO infections for census block groups using electronic health records from two major health systems in Tarrant County (Texas) from 2010-2019. We delineated recurrence across five different patterns: AmpC beta-lactamase producing bacteria (AmpC), Carbapenem-Resistant Enterobacterales (CRE), Extended spectrum beta lactamase (ESBL), Methicillin-Resistant Staphylococcus aureus (MRSA), and Vancomycin-resistant Enterococcus (VRE). We compared recurrent AMRO rates against space-time permutation model identified hotspots. We used spatial lag regressions to explore the relationship between recurrent AMRO rates and Area Deprivation Index (ADI), a measure of neighborhood inequity. Results Of 105,291 patients, 19,161 (18.2%) had at least one AMRO infection. There were 10,611 (10.1%) patients with multiple AMRO infections: AmpC = 202, CRE = 136, ESBL = 741, MRSA = 1255, and VRE = 205. We observed that AmpC, ESBL, and MRSA recurrence had the greatest co-location with spatiotemporal hotspots (Figure 1). In spatial regressions, increasing neighborhood ADI rank (increasing deprivation) was significantly associated with an increase in block group-rates of recurrent AmpC (β = 0.02), ESBL (β = 0.03), MRSA (β = 0.04) and VRE (β = 0.01) (p-value < 0.05). Conclusion We geographically and temporally identified patterns of recurrent AMROs in a large urban county and demonstrated a significant relationship between inequity and AMRO recurrence. This work can enhance our understanding of local infection dynamics and inform antibiotic stewardship. Disclosures John J. Hanna, MD, Pieces Technologies: Advisor/Consultant

P-1492. Patient Characteristics Associated with Extended-Spectrum Beta-Lactamase-Producing Uropathogens: Pooled Results from Two Phase 3 Clinical Trials of Gepotidacin for the Treatment of Uncomplicated Urinary Tract Infection

Abstract Background Uncomplicated urinary tract infections (uUTIs), usually caused by Escherichia coli (E. coli), are common infections, affecting ∼50% of women globally in their lifetime. The presence of extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales limits effective oral treatment options for uUTI. Using uropathogen susceptibility data from two randomized controlled trials (RCTs) in uUTI, we compared baseline characteristics of patients with ESBL-positive (ESBL+) versus non-ESBL uropathogens. Methods EAGLE-2 (NCT04020341) and -3 (NCT04187144) were Phase 3, double-blind RCTs of oral gepotidacin versus nitrofurantoin for uUTI. Patients were female, aged ≥ 12 years, with ≥ 2 uUTI symptoms and urinary nitrite and/or pyuria. Pretreatment clean-catch midstream urine samples were collected for quantitative culture and susceptibility. In this post-hoc exploratory analysis, patients in the intent-to-treat population (all randomized patients), with ≥ 103 colony-forming units/mL E. coli, Klebsiella pneumoniae, Klebsiella oxytoca, and/or Proteus mirabilis, were grouped by ESBL status of their uropathogen(s), per Clinical and Laboratory Standards Institute guidelines. Results Overall, 1423 patients with culture-confirmed uUTI were included in the analysis; 203 (14%) had an ESBL+ uropathogen. Baseline characteristics by ESBL status are presented in the Table, and ESBL+ uropathogen prevalence by subgroup in the Figure. Generally, versus patients with non-ESBL uropathogens, more patients with ESBL+ uropathogens were: of Asian, American Indian or Alaska Native race (though sample sizes were small); of Hispanic/Latinx ethnicity; had milder symptoms; aged > 50 years with history of recurrent urinary tract infection. Conclusion This post-hoc analysis of contemporary uUTI trial data describes baseline characteristics for patients with ESBL+ versus non-ESBL uropathogens. These data could inform future studies to identify clinical risk factors linked to ESBL+ uropathogens and improve patient outcomes. Funding EAGLE-2 was funded in part by GSK and in part with Federal funds from the US Office of the Assistant Secretary for Preparedness and Response, Biomedical Advanced Research and Development Authority (HHSO100201300011C). EAGLE-3 was funded by GSK. Disclosures Jeremy Dennison, MD PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Amanda Sheets, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Caroline R. Perry, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Florian Wagenlehner, MD, Astellas: Advisor/Consultant|AstraZeneca: Advisor/Consultant|Bionorica: Advisor/Consultant|DFG (German Research Foundation) funded research group BARICADE (FOR5427/1-466687329): Speaker|GSK: Advisor/Consultant|GSK: Principal investigator in a GSK-sponsored study|Janssen: Advisor/Consultant|Klosterfrau: Advisor/Consultant|MIP Pharma: Advisor/Consultant|OM Pharma: Advisor/Consultant|Spero: Advisor/Consultant|VenatoRX: Advisor/Consultant Mark H. Wilcox, MD, Astra Zeneca: Advisor/Consultant|Debiopharm International S.A.: Advisor/Consultant|Debiopharm International S.A.: Grant/Research Support|Ferring: Advisor/Consultant|GSK: Advisor/Consultant|GSK: Honoraria|Nestle: Advisor/Consultant|Paion: Advisor/Consultant|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria|Phico therapeutics: Advisor/Consultant|QPex Biopharma: Advisor/Consultant|Seres: Advisor/Consultant|Seres: Grant/Research Support|Seres: Lecture Fees|Summit: Advisor/Consultant|Summit: Grant/Research Support|The European Tissue Symposium: Advisor/Consultant|The European Tissue Symposium: Grant/Research Support|Tillotts: Advisor/Consultant|Tillotts: Grant/Research Support|Tillotts: Lecture Fees|Vedanta: Advisor/Consultant Nicole E. Scangarella-Oman, MS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Deborah Butler, PharmD, GSK: Employee|GSK: Stocks/Bonds (Public Company) John Breton, MCM, GSK: Employee|GSK: Stocks/Bonds (Public Company) Helen Millns, PhD, GSK: Employee|GSK: Stocks/Bonds (Public Company) Aruni Mulgirigama, MBBS, GSK: Employee|GSK: Stocks/Bonds (Public Company) Matthew Helgeson, PharmD, MBA, GSK: Employee|GSK: Stocks/Bonds (Public Company) Salim Janmohamed, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company)

162. Comparison of Clinical Risk Factors, Outcomes and Molecular Epidemiology of ESBL and non-ESBL Enterobacterales Bacteremia in Solid Organ Transplant Recipients

Abstract Background Infections caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacterales are associated with adverse outcomes in recipients of solid organ transplants (SOTr). This study aims to elucidate the risk factors, outcomes, and molecular epidemiology associated with ESBL Enterobacterales bacteremia (ESBL EB) in abdominal SOTr.Table 1:Risk Factors, Clinical Characteristics and Outcomes Methods This observational cohort study was performed on abdominal SOTr with ESBL EB (cases) and non-ESBL EB (controls) at Henry Ford Health between August 2014 and February 2023. We performed whole genome sequencing on all blood isolates; sequencing libraries were created using +QIAGEN QIAseq FX DNA Library Kit according to manufacturer’s instructions and sequenced on Illumina NextSeq 2000. Fastq files were used to determine the distribution of traits and resistance genes using the 1928 Platform. Demographic, risk factors, clinical characteristics, outcomes and molecular sequence data were evaluated. Primary outcome was 30-day mortality.Figure 1:Percentage of E. coli isolates with resistome mutations Results 56 patients were included: 31 (55%) cases and 25 (45%) controls. Liver and kidney transplant recipients were 28 (58%) and 18 (32%). Median age was 65 years and 54% were female. Risk factors for ESBL EB included liver transplant recipients (p < 0.001), second surgery < 30 days (p=0.01), primary graft dysfunction (p=0.02), and acute rejection < 3 months prior to BSI (p=0.001) (Table 1). Both 30-day (p=0.001) and 90-day (p=0.015) mortality were higher in the ESBL EB group. ST131 (57%) and ST410 (21%) were the predominant sequence types identified in ESBL E. coli isolates. Among ESBL K. pneumoniae, ST16, ST39, ST45, and ST219 were common. Resistome analysis identified β-lactam mutations in all isolates (figure 1 and figure 2). Additional resistance genes that were not phenotypically expressed in ESBL isolates were identified.Figure 2:Percentage of K. pneumoniae isolates with resistome mutations Conclusion Our study demonstrates the high mortality associated with ESBL EB in SOTr and highlights the risk factors and molecular characteristics of these infections. Clinical significance of the additional resistance genes identified needs further investigation. These findings provide insights for targeted management strategies in this high-risk population. Disclosures Mayur Ramesh, MD, AstraZeneca: Advisor/Consultant|Moderna: Advisor/Consultant|Pfizer: Advisor/Consultant

296. MDR Risk Index: Multidrug-Resistant Bacteria Probability Score for General Hospitals

Abstract Background This research endeavors to shed light on the intricate relationship between hospitalization dynamics and the probability of acquiring multidrug-resistant bacteria (MDR) by introducing a predictive tool, the Multidrug-Resistant Bacteria Probability Score.Figure 1.Estimated Risk of MDR (Multidrug-Resistant Bacteria): Point Estimates and 95% Confidence Intervals. Methods We processed cultures in the hospital laboratory using automated systems and/or microdilution methods, adhering to the BR-cast guidelines. We utilized a logistic regression model to analyze four predictive variables for MDR: length of hospitalization until the collection of biological material (days), previous hospitalization (yes/no), duration of previous hospital stays (days), and admission to the Intensive Care Unit (ICU) (yes/no). The assessment focused on 7 outcomes: MDR (any type), resistance to Meropenem (RMER), production of Klebsiella pneumoniae carbapenemase (KPC), production of Extended Spectrum Beta-Lactamase (ESBL), resistance to Polymyxin (RPOL), Vancomycin-resistant Enterococci (VRE), and Methicillin-resistant Staphylococcus aureus (MRSA).Figure 2.Logistic Regression Models Estimating MDR Risk: Results for Each Type of MDR Bacteria. Results A total of 4,247 biological samples were collected from Nov/2022 to Nov/2023: Urine (46%), Blood (12%), Tissue Fragments (11%), Bronchoalveolar Lavage (6%), Perianal Swabs (6%), Tracheal Aspirates (4%), Nasal Swabs (3%), Abdominal Fluid (2%), Tips of Central or Umbilical Catheters (2%), Wound Secretions (1%), and Other (3%). Approximately one-third (35%) of the samples were identified as MDR. Unadjusted MDR risk: 9% RMER, 5% KPC, 8% ESBL, 1% RPOL, 3% VRE, and 4% MRSA (Fig. 1). From the seven outcomes modeled, it was possible to successfully predict five of them (Fig. 2), yielding good results in terms of predictive capability (Fig. 3). However, the modeling was unsuccessful for MRSA and ESBL. Figure 4 shows simulations of MDR risk.Figure 3.ROC Curves for the Five Successful Models Predicting Multidrug-Resistant Bacteria (MDR). Conclusion The duration of hospitalization prior to the collection of biological material emerges as a crucial metric, encapsulating the temporal dimension of patient exposure to potential sources of infection. All five predictive models can be effectively integrated into the patient’s electronic health record. This integration enables the timely prediction of multidrug-resistant (MDR) infections, facilitating the implementation of targeted preventive measures based on the assessed risk level.Figure 4.Simulation of MDR Risk Evolution Over Hospitalization Time: Curves Representing MDR Risk by Patient Type Disclosures All Authors: No reported disclosures

P-1560. Risk Factors for Extended-Spectrum β-Lactamase-Producing Escherichia coli Urinary Tract Infections

Abstract Background E. coli is the leading cause of urinary tract infections (UTIs) worldwide. Antibiotic resistance among E. coli is increasing. We performed a case-control study to identify risk factors predictive of a positive extended-spectrum beta-lactamase (ESBL)-producing E. coli (ESBL-E) compared to a non-ESBL-E urine culture. Table 1 Demographic and clinical characteristics of patients with positive E. coli urine culture, Monroe County, August 2023 Methods Positive E. coli urine cultures were identified via laboratory and population-based surveillance in Monroe County as part of the CDC Emerging Infections Program in August 2023. Cases were defined as a county resident with a positive ESBL-E urine culture (resistant to ≥1 3rd-generation cephalosporin and nonresistant to carbapenems). Controls had a non-ESBL-E urine culture. All ESBL-E cases and a random sample of non-ESBL-E controls underwent medical record review to collect information on prior antimicrobial use, recent hospitalization, prior ESBL-E infection, underlying conditions, and prior long term care stay. Charlson Comorbidity Index (CCI) was calculated and categorized as low (0), middle (1-2), and high (3+). Multivariable logistic regression was used to identify independent risk factors. Results We identified 2142 patients with an E. coli urine culture; 454 underwent chart review (64 ESBL-E, 390 non-ESBL-E). Patient characteristics are summarized in Table 1. Overall, patients were mostly female (88.3%) with a median age of 61 years (IQR 39-76). Cases more commonly received antibiotics in the 30 days prior to culture (34.4% vs. 19.7%, p = 0.007), had a hospitalization in the 90 days prior to culture (17.2% vs. 8.5%, p = 0.029), had prior ESBL-E culture (25.0% vs. 3.3%, p < 0.0001), a high CCI (32.8% vs. 19.7%, p = 0.006), prior LTC stay (18.8% vs. 6.4%, p = 0.0008), and diabetes (35.9% vs. 19.5%, p=0.003). After adjusting for confounding factors, only prior ESBL-E culture (OR = 8.22; 95% CI: 3.68-18.40) and diabetes (OR = 2.32; 95% CI: 1.31-4.09) were significantly predictive of the outcome. Conclusion Patients with ESBL-E are more medically complex with increased healthcare exposure compared to patients with non-ESBL-E. Presence of a prior ESBL-E culture and diabetes were specific risk factors. Future studies are needed to better understand the collective impact of ESBL-E drivers to inform prevention strategies. Disclosures All Authors: No reported disclosures

P-1473. Amoxicillin-Clavulanate Transition Therapy in ESBL Urinary Tract Infections

Abstract Background Extended-spectrum beta-lactamase (ESBL)-producing bacteria are notoriously resistant to many antibiotics, resulting in limited treatment options for such infections. Pathogens that possess this resistance mechanism typically necessitate the use of broad-spectrum antibiotics. An often-overlooked option for ESBL urinary tract infections (UTIs) is amoxicillin-clavulanate (AMC). Currently, there is a dearth of evidence supporting its use. This analysis was done to assess the efficacy of AMC on ESBL UTI clinical cure and associated outcomes. Methods This was a retrospective chart review conducted at Scripps Memorial Hospital La Jolla between January 1st, 2018 and January 31st, 2023. Adults with UTIs caused by ESBL pathogens who completed an AMC course as UTI treatment were included. The primary outcome was clinical cure, defined by the absence of reported symptoms in hospital or clinic encounters within 7 days of AMC completion. Secondary outcomes included 30-day relapse (UTI with the same organism within 30 days), 30-day reinfection (UTI with a different organism within 30 days), or 90-day recurrence (infection with same organism within 90 days). Results A total of 196 patients were screened for enrollment, of which 100 were included. Uncomplicated cystitis (UC) was identified in 39% of patients, complicated cystitis (CC) in 17%, pyelonephritis in 25%, and catheter-associated UTI (CAUTI) in 19%. Concomitant bacteremia was identified in 9% of patients. AMC oral transition (IV step down) therapy was used in 61% of patients. Overall, 7-day clinical cure regardless UTI type was 96%. Clinical cure was 97.4% for UC, 94.1% for CC, 92% for pyelonephritis, and 100% for CAUTI. Of the patients who received AMC as primary therapy (n = 39), 100% achieved 7-day clinical cure. Clinical cure in those with an AMC MIC of ≤ 4/2 was 95.8% (n =56) and in those with a MIC of 8/4 was 96.2% (n = 53). In those with concomitant bacteremia, 77.8% (7/9) achieved 7-day clinical cure. UTI 30-day relapse, 30-day reinfection, and 90-day recurrence occurred in 17%, 8%, and 16% of patients, respectively. Conclusion Amoxicillin-clavulanate may be a promising oral transition therapy for ESBL UTIs. Larger, more robust studies should be done to analyze the efficacy of AMC as an option for primary or transition therapy for ESBL UTIs. Disclosures All Authors: No reported disclosures

P-1136. Enhancing Pediatric Care: Antimicrobial Stewardship Through 24/7 Pharmacist-Driven Rapid Diagnostics for Gram-Negative Bacteremia

Abstract Background Rapid diagnostic testing (RDT) in adult bacteremic patients (pts) provides quick organism identification, including resistance genes and can improve time to optimal antibiotic therapy (OAT). Pharmacist-driven RDT (Rx-RDT) interventions [24 hours/day and 7 days/week (24/7)] for pediatric gram-negative bacteremia GNB is limited. Objective was to evaluate outcomes before and after implementation a 24/7 Rx-RDT interventions (INT) for treatment of pediatric GNB. Methods Retrospective cohort study analyzed pediatric pts (age < 18 years) with GNB secondary to Escherichia coli, Klebsiella pneumoniae or Klebsiella oxytoca admitted to the Children’s Hospital comparing outcomes before and after implementation of 24/7 Rx-RDT INT. Pre-RDT group included pts admitted from 1/1/14-12/31/14; Pre-RDT 24/7 group embodied weekday antimicrobial stewardship (AMS) duties from 1/1/19-7/5/21; and Post-RDT 24/7 from 7/6/21-8/31/22. Polymicrobial bacteremia or concomitant fungemia were excluded. Results A total of 132 pts were included in 3 groups: Pre-RDT (n=35); Pre-RDT 24/7 (n=55); Post-RDT 24/7 (n=42). Baseline demographics were mainly similar with Hispanic predominance (Table 1). In Pre-RDT, Pre-RDT 24/7, and Post-RDT 24/7, respectively, E. coli was most common (65.7% vs 60% vs 54.8%; p=0.666) with CTX-M gene detection (associated with the extended spectrum beta-lactamase (ESBL) phenotype) in latter 2 groups (9.1% vs 26.1%; p=0.013) followed by K. pneumoniae (28.6% vs 25.5% vs 33.3%; p=0.666) with ESBL 21.4% in latter groups; p >0.05). Pts were on OAT at the time of gram-stain (GS) results in 85.7% vs 74.5% vs 59.5%; p=0.034. For pts who were not on OAT at GS results, time to OAT from blood culture collection was lowest in the Post-RDT 24/7 group (85.6 vs 26.2 vs 15.7 hours; p=0.156); time to OAT was faster from time of RDT results Post-24/7 RDT (7.9 vs 2.4 hours; p=0.028). Length of stay (19.5 vs 12.9 vs 13.3 days; p=0.601) and 30-day mortality were similar (11.4% vs 14.5% vs 9.5%; p=0.746); 30-day mortality occurred with Hispanics in all groups (18.2% vs 16.7% vs 14.4%). Night/Weekend pharmacists performed 44% of the Post-RDT 24/7 INT. Conclusion Implementation of Rx-RDT interventions 24/7 reduced time to OAT by 30% for pediatric GNB. Night/Weekend pharmacists were integral to our AMS program. Disclosures All Authors: No reported disclosures

P-890. Risk Factors Associated with Carbapenem-Resistant Enterobacteria Bacteremia and Mortality in Patients with Acute Leukemia

Abstract Background The inclusion of highly cytotoxic drugs for the treatment of acute leukemia (AL) in the last decade has exposed patients to more extended periods of severe neutropenia. The study aims to describe the prevalence and risk factors for blood-stream infection (BSI) due to carbapenem-resistant enterobacteria (CRE) in patients with AL receiving chemotherapy.Table 1.Independent risk factors for blood-stream infection due to carbapenem-resistant enterobacteria FLAG-IDA chemotherapy regimen had an OR 28.8 (CI 2.9-286.68. p=0.004) for CRE-BSI Methods The study was performed at a referral center for adult patients with cancer in Mexico City. From January 2021 to December 2022, all patients with AL treated from first to fourth line chemotherapy were included. CRE and non-CRE BSI were compared for categorical variables with Pearson's chi-square. A bivariate logistic regression analysis was performed to identify risk factors associated with mortality and isolation of CRE.Table 2.Independent risk factors for mortalityPatients with AML had an OR 7 (CI 1.26-39.23 p=0.026), isolation of CRE OR 6.8 (CI 1.17-0.03 p=0.03) and being diagnosed with invasive fungal infection (IFI) OR 5.2 (CI 1.29-26.66 p=0.02) for mortality Results One hundred ten patients were included: 62 (56.3%) with acute lymphoblastic leukemia (ALL) and 48 (43.6%) with acute myeloid leukemia (AML). 119 BSI were confirmed, 41 (34%) blood isolates were antimicrobial resistant, 23 (56.1%) had extended-spectrum beta-lactamases (ESBL), and 16 (39%) had CRE. BSIs were classified as 70 (58.8%) Mucosal Barrier Injury Laboratory-Confirmed Bloodstream Infection (MBI-LCBI), 24 (20.1%) secondary, 23 (19.3%) catheter-related and 2 (1.6%) primary. Of the 23 (56.1%) isolates with ESBL and 16 (39%) CRE, all were classified as MBI-LCBI, as were two (4.9%) methicillin-resistant S. aureus. Overall, 30-day mortality was 9.2%, and at 24 weeks, 16.8%. In the bivariate analysis, receiving a FLAG-IDA had an OR 28.8 (CI 2.9-286.68. p=0.004) for CRE-BSI (Table 1). For mortality, having AML had an OR 7 (CI 1.26-39.23 p=0.026), CRE BSI isolates OR 6.8 (CI 1.17-0.03 p=0.03), and being diagnosed with invasive fungal infection (IFI) OR 5.2 (CI 1.29-26.66 p=0.02) (Table 2). Kaplan-Meier model comparing patients with and without CRE-BSI showed a mean survival of 17.8 months in CRE-BSI vs. 23.4 months without CRE-BSI, although non statistical significance (Figure 1).Figure 1.Kaplan-Meier survival analysisKaplan-Meier model comparing patients with and without CRE-BSI showed a mean survival of 17.8 months in CRE-BSI vs. 23.4 months without CRE-BSI, although without statistical significance Conclusion In this cohort, overall mortality was associated with AML, having CRE isolated in blood, and having been diagnosed with IFI. Having a CRE-BSI was associated with receiving FLAG-IDA. This highly myelosuppressive chemotherapy regime has become a niche for antimicrobial resistance development in our institution. Disclosures All Authors: No reported disclosures

P-1762. Assessing the Clinical Impact of Carbapenem Pre-authorization in a High ESBL Prevalence Setting: A Focus on the Middle East

Abstract Background Hospitals commonly employ preauthorization as a strategy to optimize carbapenems utilization. However, there is paucity of data regarding carbapenem restriction in environments with a high prevalence of extended-spectrum beta-lactamase (ESBL) organisms. This study aims to assess the impact of implementing a preauthorization policy for carbapenems on patient clinical outcomes and appropriateness of use. Methods An observational retrospective cohort study comparing data collected for patients from pre-restriction period between December 2021 and May 2022, and post-restriction period between June 2022 and December 2023 who were prescribed carbapenems including ertapenem or meropenem. The restriction policy was implemented in June 2022. We included adult patients ( > 18 years old) with active infections in acute care units (ACU). Results A total of 244 patient were included in the study with 131 in pre implementation period and 113 in post implementation period. The appropriate indication of carbapenems use was significantly higher in the post-restriction group 69.9% (79) vs the pre-restriction group 55.7% (73) (P=0.025). No significant difference was found between the two groups in terms of appropriateness of treatment duration (P=0.425). Antibiotic de-escalation was significantly higher in the pre-restriction group 60.3% (79) vs the post-restriction group 35.4% (40) (P< 0.001). The 30-day all cause mortality was significantly lower in the post-restriction group 7.1% (8) vs the pre-restriction group 19.8% (26) (P=0.005). Length of hospital stay (LOS) was significantly lower in the post-restriction group compared to the pre-restriction group; 6 vs 9 days (P=0.002). Furthermore, the 30-day readmission rate was 32.1% (42) of patients in the pre-restriction group vs 20.4% (23) in the post-restriction group (P=0.043). Table 2 Conclusion Despite ESBL high prevalence, preauthorization policy for carbapenems prescription showed efficacy to optimize their use in terms of, both, appropriateness, and duration. Lower 30-day mortality, LOS and readmissions within ACU patients also confirmed better clinical outcomes. Larger studies are needed to corroborate these findings. Disclosures All Authors: No reported disclosures

P-738. A Microbiological Profile of Necrotizing Fasciitis at a Tertiary Referral Hospital in a Low/Middle Income Country

Abstract Background : Necrotizing fasciitis (NF), an uncommon, fatal infection of the skin and soft tissues, carries a significant mortality risk, with rates reaching as high as 76% despite prompt surgical interventions. While polymicrobial infections were more likely to be encountered, few studies reported a monomicrobial predominance. Despite its relevance, there is a notable lack of data in the Eastern Mediterranean region. We aimed to investigate the microbiological profile among patients diagnosed with necrotizing fasciitis in a tertiary referral center in Lebanon, with a particular focus on Multidrug-resistant organisms (MDROs) and Antimicrobial Resistance (AMR), given their increasing prevalence and the challenges they pose in clinical management.Table 1:Distribution of Organisms Methods A retrospective chart review of hospitalized cases between 2011 and 2021. The study population included adult patients diagnosed with NF during this period. Data included microbiological characteristics, with focus on Multidrug-resistant organisms (MDROs).Figure 1:Yearly Trend of MDROs Among Isolated Organisms Results 41 cases of NF were identified showing a mortality rate of 37%. 46 % of cases had polymicrobial infections versus 42% monomicrobial. The predominant gram negative pathogen was E.coli in both types of infections followed by the gram positive pathogen, Enterococcus species. No difference in the type of infection was noticed in the survival group compared to a predominance of polymicrobial infection in the non-survival group. Fungi were recovered represented in 5.4% of cases and were part of a polymicrobial infection. Out of all the isolated organisms, 21.2% showed patterns of resistance (Extended Spectrum Beta Lactamase, Multidrug resistant, Vancomycin Resistant Enterococcus, and Carbapenem Resistant Enterobacteriaceae) with a yearly incremental rise. Conclusion This 10-year study emphasizes the urgency of prompt surgical intervention and tailored antibiotic treatment for NF, particularly in the context of increasing AMR and the presence of MDROs, contributing crucial regional data on NF demographics, comorbidities, and microbiology Disclosures All Authors: No reported disclosures

P-279. An Online Registry of Carbapenemase Producing Gram Negative Organisms for Evaluating the Clinical Profile, Outcomes and Mechanisms of Resistance in Two Tertiary Level Hospitals (ORiGiN Study): An Interim Analysis

Abstract Background Infections with gram-negative carbapenem-resistant organisms (CRO) are an emerging global problem, but little is known about CRO in the Philippines. This study aims to build a registry and describe the clinical profile and molecular mechanisms of resistance of carbapenem-resistant infections. Methods This prospective study will enroll patients from two tertiary-level hospitals from 01/01/2023 to 12/31/2025. Admitted patients >18 years old with documented CRO infection confirmed by phenotypic resistance and molecular testing are included in this year-1 analysis. Results 150 patients were enrolled in the first year. Around half (79/150, 54.7%) were female. Median age was 60 (range 21-94) years. Many had at least one comorbidity -- hypertension (90/150 65.2%), diabetes mellitus (45/150, 32.6%), and congestive heart failure (42/150, 30.4%). Most patients experienced CR infection only once (123/150, 82%), while a few (27/150,18%) had two or more. Infections originated from respiratory (63.3%), blood (22.6%), or urinary (16.4%) sites. Higher mortality was seen among patients who received three or more antibiotics (119/150, 57.1%) or had prolonged treatment ( >15 days) during admission (53.1%). Resistance to fluoroquinolones (ORadjusted=4.32 (95% CI: 1.11, 16.81); p=0.035) and older tetracyclines (ORadjusted=5.49 (95% CI: 1.08, 27.93); p=0.040) were significantly associated with mortality in the adjusted models. Only 9 out of 169 (5.32%) were Extended Spectrum Beta Lactamase (ESBL) producing. 40/169 (23.7%) were tested for carbapenem resistance genes and the two most common antimicrobial resistance genes were blandm (n= 17) and blaoxa51 (n=20). Conclusion The study provides initial data on the local epidemiology and molecular mechanisms of resistance of gram-negative CRO. Interim results show that CR infections affect the older population and are mainly respiratory in origin. Multiple antibiotics, prolonged therapy, and the use of fluoroquinolones and tetracyclines were all associated with higher mortality. Class D (OXA-51) and Class B (NDM) beta-lactamases were most frequently isolated. Disclosures All Authors: No reported disclosures

P-2314. Assessing Hazard Ratio of Recurrent Spontaneous Bacterial Peritonitis: Impact of Antibiotic Prophylaxis in Cirrhotic Patients

Abstract Background Spontaneous bacterial peritonitis (SBP) is a severe infection of the ascitic fluid in individuals with advanced liver disease and ascites. The American Association for the Study of Liver Diseases recommends antibiotic (abx) prophylaxis (ppx) for patients with a history of SBP, low ascitic fluid protein (< 1.5 g/dL), or advanced cirrhosis with ascites. However, prophylactic antibiotics cause collateral damage and their efficacy in reducing SBP recurrence remains uncertain. This study assesses the recurrence rates between groups receiving prophylaxis and those without. Methods Single centered, retrospective cohort study aimed to estimate the hazard ratio (HR) for recurrent SBP in patients with and without SBP ppx. Patients meeting criteria of cirrhosis with documented ascites and polymorphonuclear leukocyte count ≥ 250 cells/µL were randomly selected between 2017 to 2023. The primary outcome was time to recurrent SBP. Cox proportional hazard models were used to estimate the HR and 95% confidence intervals (CIs). Results 38 patients were included, 4 patients received SBP ppx. The HR for recurrent SBP was not statistically significant [0.765 (95% CI -1.58, 1.04)] between use of SBP ppx and those with no ppx abx. This analysis was controlled for age, gender, alcohol use, cancer, diabetes, chronic kidney disease, chronic lung disease, autoimmune disease, and HIV status. Incidentally we found that, of the 4 patients who received prophylaxis, 2 developed extended spectrum beta lactamase (ESBL) producing gram negative infections in either ascitic or blood cultures. Conclusion Our analysis did not demonstrate a statistically significant difference in the hazard of recurrent SBP between patients with versus without ppx. SBP ppx was found to have potential risk of recurrent SBP with more resistant ESBL-producing pathogens for those on SBP ppx. Additional study may be warranted to further elaborate the benefit vs risk of SBP ppx in terms of development of resistance. Disclosures All Authors: No reported disclosures

P-408. Utility of a Large Language Model for Identifying Central Line-Associated Bloodstream Infections (CLABSI) Using Real Clinical Data at Stanford Health Care

Abstract Background Central line-associated bloodstream infections (CLABSI) surveillance can be subjective and time-consuming. Large language models (LLMs) are advanced artificial intelligence systems with potential to assist healthcare professionals in classification tasks. Stanford Health Care recently implemented one of the first secure LLMs, powered by OpenAI’s GPT 4.0, cleared for sensitive health data. We assessed its performance in classifying CLABSI cases.Figure 1:Confusion Matrix of LLM Performance in CLABSI Classification. Methods We selected 40 patients flagged by our surveillance system for CLABSI review from November 2023–March 2024: 20 CLABSIs, consecutively identified, and 20 not-CLABSIs (randomly sampled). We prompted the LLM to determine if patients met the NHSN definition for CLABSI and provided the blood culture results that triggered the alert and the last 2 progress notes from the primary care team at the infection window end (within 3 days after the first positive test). We compared the secure LLM's determinations with those of infection preventionists.Table 1.Cases in which the LLM did not agree with IP assessment for CLABSI.*Community-onset: Blood cultures obtained within 2 days of admission.+NHSN guidelines list Fusobacterium nucleatum as an MBI organism (https://www.cdc.gov/nhsn/pdfs/pscmanual/17pscnosinfdef_current.pdf)Abbreviations: BSI, bloodstream infection; CLABSI, central line-associated infection; CoNS, coagulase-negative Staphylococci; ESBL, extended-spectrum beta lactamase; HIDA scan, IP, infection preventionist, LLM, large language model; MBI, mucosal barrier injury; MSSA, methicillin-susceptible Staphylococcus aureus; NHSN, National Healthcare Safety Network. Results Across 20 CLABSI-positive and 20 CLABSI-negative cases reviewed, the LLM accurately identified 16 of 20 CLABSIs and 7 of 20 not CLABSIs. The sensitivity was 80% (95% CI 57.6%–92.9%), specificity was 35% (95% CI 33.3%–86.5%), and the agreement rate was 57.5% (95% CI 41.2%–73.3%). Among 17 discordant cases, 11 involved clinical data available in the chart but unavailable to the LLM—admission information (4 false-positives), matching organisms (4 false-positives), and central line or symptom status (2 false-negatives, 1 false-positive). If this information was available to the LLM, we expect an adjusted sensitivity of 90% (18/20) and adjusted specificity of 80% (16/20). The remaining discordant cases involved misclassifications of organisms and incorrect identification of infection sources by the LLM. The mean review time by infection preventionists was 75 minutes (SD 48.7 minutes) compared to 5 minutes using the LLM. Conclusion An LLM not specifically trained for CLABSI classification showed high sensitivity using limited patient data. LLM case review required 5 minutes, versus 1 hour for traditional review. These results suggest LLMs could serve as a "first-pass" screening tool for CLABSI detection, helping infection preventionists narrow records needing human review. Disclosures All Authors: No reported disclosures

P-1123. Characterization of microbiological isolates in the newborn unit of the San Ignacio university hospital between 2018 and 2022

Abstract Background Identifying local microbial profiles and antibiotic sensitivities is an important part of antimicrobial stewardship programs in order to prevent overuse of antibiotics. The purpose of this study was to characterize the microbiological isolates from patients hospitalized in the newborn care unit of the Hospital Universitario San Ignacio from January 1, 2018 to December 31, 2022. Total number of microorganisms isolated 1 Methods An observational, descriptive, historical single cohort study was conducted. Positive cultures of sterile samples (blood, urine, spinal fluid) from patients hospitalized. Demographic, clinical, and microbiological data of patients with positive cultures were also collected. Results A total of 207 positive cultures of sterile samples were identified (97 blood, 108 urines, 2 spinal fluid). The most frequent pathogens isolated were E. coli 28.9%, S. epidermidis 27%, Enterococcus faecalis 11.5%, Klebsiella pneumoniae 8.2% and Staphylococcus aureus 4.8%. E. coli and S. epidermidis being the main microorganisms isolated 28% each were the main pathogens associated with neonatal sepsis (NS). NS was predominantly late-onset >72 hours 94.6%. Early-onset sepsis was less common 5.3% and was associated with E. coli 5.4% and S. agalactiae 18.1%. Healthcare-associated infections (34.7%), and catheter-associated bloodstream infections (CLABSI) were the most common. Congenital heart disease (P = .000) was the main comorbidity related to CLABSI, as well as gastroschisis (P = 0.002) and intestinal atresia (P = 0.033) Multidrug-resistant (MDR) microorganisms were isolated in 12 instances (5.8%). Extended Spectrum Beta-Lactamase (ESBL) was 50%. Congenital heart disease was the only comorbidity with a statistically significant relationship with infection by MDR microorganisms (P = 0.026). Clinical and sociodemographic characteristics of the multidrug-resistant microorganism population. Conclusion This is the first study in our environment to know the basal factors of infections in a population at risk, the patterns of resistance and possible association with the most prevalent pathologies and, based on this, to define the strategies of antimicrobial stewardship. Disclosures All Authors: No reported disclosures

P-1345. Risk Factors for Ceftriaxone Resistant E. coli or K. pneumoniae Infections in Floor Patients

Abstract Background In 2019, 1.3 million deaths worldwide were linked to antimicrobial resistant organisms. Resistant organisms are associated with poor outcomes including increased mortality and length of stay (LOS). Identification of local risk factors predisposing for resistant organisms can lead to rapid antimicrobial optimization. Patient Population Methods In this retrospective, single center, observational cohort study, floor patients with ceftriaxone (CRO) resistant E. coli or K. pneumoniae via broth microdilution were screened from January 2022 to October 2023. Exclusion criteria included urine isolates, extended spectrum beta-lactamase (ESBL) or CRO resistant E. coli or K. pneumoniae isolate within 6 months of index culture, and intensive care unit (ICU) admission at time of index culture. The primary outcome was to identify risk factors for CRO resistant E. coli and K. pneumoniae in floor patients. Secondary outcomes included 14-day all-cause mortality, ICU admission rate, hospital LOS, and 30-day readmission rate. A list of patients was generated via MedMined™. REDCap™ was used for data collection. All statistical analyses were performed using IBM SPSS™. Significance was defined at p< 0.05. Multivariate Logistical Regression Results 118 patients were included in the statistical analyses. The following risk factors found to be statistically significant were: fluoroquinolone (FQ) (p< 0.01), ceftriaxone (CRO) (p< 0.01), or sulfamethoxazole-trimethoprim (SMX-TMP) (p< 0.01) use within 90-days of index culture; chronic obstructive pulmonary disease (p=0.01); ventilator or tracheostomy use at admission (p=0.03); active hematologic malignancy (p=0.01); poor functional status at admission (p=0.02); percutaneous endoscopic gastrostomy tube at admission (p=0.01); admission from a skilled nursing facility (SNF) (p=0.01). The significant risk factors were included in the multivariate logistic regression. FQ use (95% CI 0.98-16.35, p=0.05), SMX-TMP use (95% CI 2.08-29.24, p< 0.01), hematologic malignancy (95% CI 1.40-129.36, p=0.02), and admission from a SNF (95% CI 1.29-36.27, p=0.02) were found to meet statistical significance. Conclusion FQ use and SMX-TMP use within 90-days of index culture, hematologic malignancy, and admission from a SNF were found to be independently associated with ceftriaxone resistance. Disclosures All Authors: No reported disclosures

P-341. Multidrug-Resistant Organism Sharing Among Nursing Home Roommates

Abstract Background Nursing homes are high-risk settings for multidrug-resistant organism (MDRO) prevalence and spread. We investigated whether nursing home roommates were more likely to carry the same MDRO compared to non-roommates. Methods We conducted a secondary analysis of 44 nursing homes in two studies (Protect Trial-Miller NEJM 2023; SHIELD-Gussin JAMA 2024) involving universal chlorhexidine bathing and nasal iodophor. We used MDRO status from baseline (2016-17) and end-intervention (2018-19) visits where 50 residents were sampled at random at each nursing home. Sampling included bilateral nares swabs processed for methicillin-resistant Staphylococcus aureus (MRSA), and axilla/groin swabs processed for MRSA, vancomycin-resistant Enterococci (VRE), and extended-spectrum beta-lactamase (ESBL) producers. We used generalized estimating equations with alternating logistic regressions to assess the odds ratio (OR) for each MDRO while clustering by nursing home. These ORs are the relative odds of one person being positive (outcome) given that the paired person is positive (exposure), divided by the odds of being positive if the paired person is negative. We estimated separate values when the two people are roommates and when they are non-roommates. Models adjusted for age, gender, post-acute status, need for full care assistance, presence of an indwelling device, MDRO history, and baseline vs. decolonization period. Shared room assignments (cohorting) due to known history of the specific MDRO being modeled were excluded. Results The 44 nursing home sample included 4851 residents who were roomed in 180 single rooms, 1945 doubles, 874 triples, 93 quads, four 5-bed rooms, and six 6-bed rooms. The Table shows significantly higher ORs of concordant MDRO carriage among roommates than among non-roommates for each MDRO. Conclusion Roommates in nursing homes are significantly more likely to carry the same MDRO versus non-roommates, indicating potential transmission within shared rooms. Disclosures Ken Kleinman, ScD, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work Raveena D. Singh, MA, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work Raheeb Saavedra, AS, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work Susan Huang, MD, MPH, Xttrium Laboratories: Conducting studies in which participating hospital patients received contributed antiseptic products outside the submitted work