bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1333. Influence of Allocation Proportion of Intervention and Control on Results Analyzed Using the Cox Proportional Hazard Model: A Pilot Meta-Analysis Using Actual Clinical Trials
Authors: Takeishi Soichi , Inoue Tatsuo , Miyamura Koichi 
Published: January 2025

Abstract

Background
In reports assessing the effect of an intervention (I) on COVID-19–related endpoints using the Cox proportional hazard model, “allocation proportions of I and control (C)” vary. The effect of these allocation proportion on results analyzed using Cox regression in actual clinical trials is unknown. Therefore, we conducted a pilot meta-analysis of clinical trials to investigate this effect.
The correlations between metrics

Methods
Articles published in The New England Journal of Medicine were included as part of a pilot meta-analysis if the following conditions were satisfied: 1. assessing endpoints related to COVID-19, and 2. using Cox regression. We referred to “upper limit of 95% confidence interval (CI) of hazard ratio (HR) (U95%CI) − lower limit of 95%CI of HR (L95%CI)” as the 95%CI range. Partial regression coefficients (β) were calculated as Loge(HR), and the standard error of β was estimated using ((Loge(U95%CI) – Loge(HR)) ÷ 1.96 + (Loge(HR) − Loge(L95%CI)) ÷ 1.96) ÷ 2, denoted as eSE. We calculated eSE ÷ an absolute value of β (eSE/|β|). The number of subjects (n) in an intervention group (nI) ÷ (nI + n in a control group (nC)) × 100 was termed “intervention proportion % (IP)”, and nC ÷ (nI + nC) × 100 was termed “control proportion % (CP)”. We calculated the absolute value of 40 − CP (|40 − CP|) and 40 – IP (|40 – IP|). For HR&lt; 1, “HR&lt; 1 adjusted group” (HR&lt; 1aG) retained the original metrics, while the “HR &gt;1 adjusted group” (HR &gt;1aG) used metrics calculated with the reciprocal of HR and its 95%CI (e.g. 0.50 (0.20-0.80) → 2.00 (1.25-5.00)). For HR &gt;1, HR&lt; 1aG used metrics calculated with the reciprocal of HR and its 95%CI, while HR &gt;1aG retained the original metrics.

Results
We included 50 outcomes from 22 studies. The figure shows the correlations between metrics. In HR&lt; 1aG, |40 − CP| correlated with the 95%CI range (r=0.62, p&lt; 0.001), whereas |40 – IP| did not correlate with the 95% CI range (r=0.01, p=0.93) in HR &gt;1aG. In HR&lt; 1aG, |40 − CP| correlated with the eSE/|β|, and |40 − IP| correlated with the eSE/|β| in HR &gt;1aG (both r=0.63, p&lt; 0.001).

Conclusion
The present study results may indicate that extremely biased allocation proportions of I and C diminish the credibility of HR. Replacing eSE/|β| with 95%CI range may not accurately assess this diminished credibility.

Disclosures
All Authors: No reported disclosures
P-1338. Don't You Forget About Me: Older Patients with Substance Use Disorder -- Have We Left Them Behind on Screening?
Authors: Yu Diana , Streifel Amber C , Varley Cara D 
Published: January 2025

Abstract

Background
Oregon has seen increasing incidence of sexually transmitted infections [e.g. HIV, syphilis, gonorrhea, chlamydia (GC/CHL), hepatitis C (HCV)], as well as outbreaks associated with vaccine preventable infections [e.g. hepatitis A (HAV), B (HBV)]. Limited data are available on routine screening and vaccination rates despite guidelines expanding screening, especially in high-risk patients such as those with substance use disorder (SUD). This study aims to determine rates of screening in persons with SUD.Table 1.Patient Demographics by Year of First Consultation

Methods
Single-center, retrospective cohort study in Portland, Oregon, USA. Patients aged 12-100 years with an Addiction Medicine consultation between January 1, 2015-March 31, 2024 were included. Data abstracted included patient demographics, payor status, and laboratory results for GC/CHL, syphilis, HAV, HBV, and HCV, and HIV. Chi-squared test was used to analyze differences in testing rate testing by age group.Table 2.Screening Rates and Results by Age Group

Results
A total of 5630 patients met inclusion criteria (Table 1). For GC/CHL screening, 887 patients had testing; 32 and 24 of 1228 tests were positive, respectively. For syphilis screening, 2364 patients were tested; 260 of 3539 tests were reactive. HAV serology was performed in 1566 patients; 694 were immune, 596 non-immune, 2 with active infection, and 274 were IgM negative at initial testing. There were 3998 tests for HBV; however, 2709 were incomplete panels (e.g. missing HBVsAb). Of the 903 patients with a full panel, 264 were immune, 92 had prior infection, 11 with acute/chronic infection, and 536 non-immune at initial testing. 4206 HCV tests were performed in 3043 patients with 632 new or recent diagnoses during the study period. 4603 HIV screening tests were performed in 2728 patients, with 13 new diagnoses. Patients aged 55 years and older were less likely to receive testing (Table 2).

Conclusion
Despite guidelines recommending frequent screening in high-risk patients, it appears to be limited at this institution. Furthermore, screening tests revealed several opportunities for healthcare intervention (e.g. vaccination) thus efforts should be made to secure access to testing. Future directions should include ordersets to ensure proper testing and follow through of results, as well as education and feedback to providers of screening results.

Disclosures
All Authors: No reported disclosures
P-1346. Identification of aminoglycoside 6′-N-acetyltransferase type Ib small molecule inhibitors using mixture-based combinatorial libraries and structure-activity relationship studies
Authors: Sklenicka Jan , Tran Tung , Magaña Angel J , Ramirez Maria Soledad , Donow Haley , LaVoi Travis M , Mamun Yasir , Chapagain Prem , Santos Radleigh , Pinilla Clemencia , Giulianotti Marc , Tolmasky Marcelo 
Published: January 2025

Abstract

Background
The aminoglycoside 6′-N-acetyltransferase type Ib [AAC(6’)-Ib] confers resistance to amikacin and other relevant aminoglycosides in Gram-negatives. To identify small molecule inhibitors of AAC(6’)-Ib that would overcome resistance, we utilized a strategy incorporating mixture-based combinatorial libraries, scaffold ranking, and positional scanning, followed by structure-activity relationship analysis. After identification of pyrrolidine pentamine by scaffold ranking, we isolated a compound substituted by two S-phenyl groups, an S-hydroxymethyl group, and a 3-phenylbutyl group at the R positions (compound 2700.001) (Fig 1). Herein, we describe a structure-relationship analysis of this compound.
Figure 1
Chemical structure of compound 2700.001

Methods
Initial inhibition assessment was done by measuring OD600 of A. baumannii A155 cultures at a single dose of compound. Checkerboard assays were done in triplicate, with each dose combination tested twice. The data were processed to eliminate any antibacterial effect exerted by the inhibitor.

Results
Single substitution of functionalities at R positions along the core scaffold of compound 2700.001 showed that position R5 is the most tolerant to changes. The replacement of 3-phenylbutyl by 4-phenylbutyl resulted in compound 2700.003, equally active to 2700.001. Modifications at all other locations produced weaker inhibitors, while truncations of the scaffold resulted in inactive compounds. Testing compounds with double or triple substitutions confirmed the critical role of the S-phenyl group at position R1. No compounds with higher inhibitory activity were found. Using molecular docking, the relationship between ΔG (Kcal/mol) values for each compound and inhibitory activity was studied, with results indicating a significant correlation.

Conclusion
Using mixture-based combinatorial libraries, the scaffold ranking approach, and the positional scanning strategy, we identified an inhibitor of AAC(6’)-Ib that can overcome resistance to amikacin in Gram-negatives. Furthermore, structure-activity relationship studies led to the identification of a second inhibitor, while also giving direction for further improvements to the molecule toward developing stronger inhibitors.

Disclosures
All Authors: No reported disclosures
P-1352. Epidemiology and Clinical Profile of Infections Caused by Carbapenem-resistant Gram-negative Bacilli Identified by a Rapid Molecular Method in a Referral Hospital in Nicaragua
Authors: Zúniga-Gaitán Josué , Marenco-Avilés Sunaya , Gavarrete-Rivas Kevin , Porras-Cortés Guillermo D 
Published: January 2025

Abstract

Background
Bacterial resistance is a public health problem and resistance to carbapenems has a special connotation and it is important that each institution and country establish the characteristics of these infections. The objective of this study was to determine the epidemiology, clinical profile, and outcome of infections caused by carbapenem-resistant microorganisms in a referral hospital in Nicaragua.Figure 1.Prevalence of Carbapenemases Detected by Xpert Carba-R and Types of Carbapenemases in Clinical Samples

Methods
An ambidirectional cohort study was carried out between January 2019 and November 2023 at the Dr. Fernando Vélez Paiz Hospital (Managua, Nicaragua) including all patients with infection and a clinical sample that had been processed directly by the Xpert Carba-R® rapid diagnostic molecular method to detect carbapenemases of the NDM, KPC, VIM, IMP, and OXA-48 type. Patients of the Surgery, Orthopedics, Internal Medicine, and Critical Care Department were included. The clinical data were obtained from the hospital's electronic medical record system.Figure 2.Number of Carbapenemases Detected by Patients

Results
A total of 346 patients with infectious processes had their clinical samples processed directly by Xpert Carba-R®, and 56 (16.1%) had a carbapenem resistance gene detected (Figure 1). By type of infection, resistance to carbapenems was 36% in ventilator-associated pneumonia, 34% in intra-abdominal infection, and 30% in surgical site infection. NDM carbapenemase was present in 91.1% of patients, and KPC in 27% (Figure 1). More than one type of carbapenemase was found in 26.8% of patients. In 4% of the patients 3 types of carbapenemases was found. (Figure 2). The most frequently identified bacterium was K. pneumoniae (36.4%), followed by E. coli (16.9%) (Figure 3). Mortality in patients with carbapenem resistance was 58.9%. Risk factors for mortality were infection with the presence of two carpanemases, requiring mechanical ventilation on admission, presence of shock on admission, Charlson index ≥ 3 points, among others (Table 2).Figure 3.Gram Negative Bacilli Identified in Clinical Samples with Carbapenemases Detected by Xpert Carba-R

Conclusion
The prevalence and mortality associated with the presence of carbapenemases detected by the molecular method used were high. The most prevalent carbapenemase was NDM. Different factors were associated with mortality, including shock on admission, invasive devices (eg: vascular catheter), patient comorbidities, and the presence of 2 different types of carbapenemases in the infection.Table 1.Risk Factors for Mortality in Patients with Infection with Gram Negative Bacilli Resistant to Carbapenems Detected by Xpert Carba-R

Disclosures
All Authors: No reported disclosures
P-1354. Carbapenemase Gene Detection in Clinically Significant Pseudomonas aeruginosa Isolates from A Tertiary Care Health Center: A Prospective Study
Authors: Kumar Deepak , Chaudhary Monika , Gadepalli Ravisekhar , Vaishnavi meruvu Hari , aggarwal alisha , Tak Vibhor , Bohra Gopal Krishna , Meena Durga Shankar , Midha Naresh Kumar , Samantaray Subhashree , Solanki Hitendra Pal , Kothari Nikhil , Bhatia Pradeep , Garg M K 
Published: January 2025

Abstract

Background
Pseudomonas aeruginosa is a leading pathogen causing widespread hospital acquired infections worldwide. As WHO has also designated Carbapenem resistant Pseudomonas aeruginosa as one of three Critical Priority Pathogen, we decided to conduct a study on the Pseudomonas aeruginosa isolates to find out the presence of carbapenemase genes using RT-PCR and to find out the relation between the phenotypic assessment of carbapenem resistance with genotypic detection of carbapenemase genes.

Methods
Total 41 patients were included in this prospective observational study done for 6 months from 1st July 2023 to 31st December 2023. Pseudomonas aeruginosa isolates from the patients with age &gt;18 years, ICU admission for more than 48 hours and absence of any coinfection were included and those patients with polymicrobial infections and multisite infections were excluded. Isolates were obtained from the blood, respiratory and pyogenic samples and antimicrobial susceptibility was done by VITEK for various antimicrobials and broth microdilution for colistin. The bacterial colony was used for DNA extraction using Bacterial Genomic DNA Extraction Kit in accordance with the manufacturer’s instruction. Multiplex RT PCR was done to detect genes blaVIM, blaNDM, blaKPC and blaIMP.

Results
Out of 41 isolates, as depicted in figure 1, blaIMP was most common gene found in 26(63.41%), followed by blaNDM in 20(48.7%) isolates. Combination of blaNDM and blaIMP was found in 12 (29.2%) and blaNDM with blaKPC in 3(7.3%) patients. As shown in table 1 even in isolates which were found pan sensitive to all antimicrobials in VITEK were also harboring genes for carbapenemase. blaIMP was found in 9(69%) of these isolates out of 13 pan sensitive ones. Attributable mortality according to phenotypic resistance is described in table 1. Figure 2 is amplification plot of blaNDM by RT PCR of one of the isolates.

Conclusion
We found presence of blaNDM and blaIMP genes in our isolates of Pseudomonas aeruginosa as compared to global presence of blaKPC and blaVIM. High prevalence of carbapenemase genes even in pan-sensitive isolates can be attributed to excessive use of carbapenems and larger studies are required to find out its impact on clinical outcome.

Disclosures
All Authors: No reported disclosures
P-1356. Risk factors associated with community-onset infections due to clinically moderate to high-risk AmpC producing organisms
Authors: Baalbaki Nadeem , Mohsen Mahinaz , Al Hadidi Moayad , Boyle Leigh Ann , Sackey Joachim , Salim Tanzila 
Published: January 2025

Abstract

Background
The Enterobacterales order is among the most common group of bacteria relevant in clinical practice. Among them are inducible AmpC-producing Enterobacterales (AE). This unique group of bacteria may produce AmpC enzymes if induced in the setting of certain beta-lactam antibiotics, limiting the number of effective treatment options. Previous data have suggested that inappropriate antibiotics used empirically for AE increase the risk of treatment failure, but limited data are available to describe the risk factors associated with community-onset (CA) AE to help guide empiric therapy.

Methods
This was a retrospective case-control study of patients admitted to University Hospital from 2021 to 2023 with a CA Enterobacter cloacae, Klebsiella aerogenes, or Citrobacter freundii clinical isolate. The first clinical isolate was included for each patient. Patients were matched at a rate of 1:1 to a patient with a CA Enterobacterales organism without 3rd generation cephalosporin resistance. Patients were matched according to infection, age (+/- 5 years), and sex at birth. The primary outcome was to evaluate risk factors associated with CA AE infections.

Results
A total of 176 patients were included in this study, 88 in each group. In a univariate analysis, prior hospitalization (OR, 3.3 [95% CI, 1.72-6.4]), surgical intervention (OR, 5.8 [95% CI, 1.62-20.9]), exposure to any antibiotic (OR, 2.2 [95% CI, 1.15-4.14]), exposure to 1st generation cephalosporins (OR, 2.8 [95% CI, 1.09-7.07]), and exposure to cefepime (OR, 3.3 [95% CI, 1.03-10.72]) within 3 months were associated with an increased risk of a CA AE. Being Hispanic or Latino was associated with a decreased risk of having a CA AE in a univariate analysis and was the only variable statistically significant in a multivariable analysis (OR, 0.34 [95% CI, 0.15-0.74]).

Conclusion
Our findings suggest that patients with prior hospitalization, surgical intervention, exposure to any antibiotic, to 1st generation cephalosporins, and to cefepime within 3 months may be associated with an increased risk of a CA AE in a univariate analysis, although no association was seen in a multivariable analysis. In contrast, Hispanic or Latino patients may be at a decreased risk for CA AE. A larger sample size may be warranted to validate these findings.

Disclosures
All Authors: No reported disclosures
P-1359. Epidemiology of Carbapenem Resistant Enterobacterales in Monroe County, NY 2016-2023
Authors: Tsay Rebecca , Dietz Jenna , Felsen Christina B , Dumyati Ghinwa 
Published: January 2025

Abstract

Background
Carbapenem-resistant Enterobacterales (CRE) infections pose an urgent threat due to the limited treatment options and the potential for resistance spread among carbapenemase producing (CP) CRE strains.

Methods
We conducted active population-based surveillance for select Enterobacterales species resistant to ≥ 1 carbapenem from a normally sterile site or urine in Monroe County, NY as part of the CDC Emerging Infections Program. Epidemiologic data were collected through medical record abstraction. Cases were classified as hospital onset (HO) if they occurred 72 hours after hospital admission, healthcare-associated community-onset (HACO) cases if they had a prior healthcare risk factor, or community associated (CA). CRE isolates were tested at CDC or Northeast Antimicrobial Resistance Laboratory Network.

Results
From 2016-2023, CRE incidence increased 135% from 8.8 to 20.7 per 100,000 population with 895 incident CRE cases identified in 745 unique patients. Patients were mostly non-Hispanic (89.2%), White (82.1%) and female (67.8%). Urine was the most common source (92.7%). 58.1% of cases were HACO, 28.6% CA and 13.2% HO. Urinary tract abnormalities (58%) and recurrent UTIs (32.6%) were prevalent. Prior healthcare exposures including hospitalization (57.2%), surgery (28.5%), and skilled nursing home stay (22.1%) were common in healthcare associated cases. Few (2%) had a history of international travel. Hospital onset cases were more likely to have CRE isolated from blood (21.2%), require ICU admission (33.1%), and die within 90 days of their infection (34.4%). 272 CRE isolates underwent carbapenemase testing, of those, 78 (28.7%) were CP-CRE: 71.1% blaKPC, 19.3% blaNDM, and 9.6% blaOXA48 with documented emergence of blaNDM CP in 2021. Only 6 (9.5%) of CA isolates were CP-CRE compared to 18 (40%) of HO, and 54 (33.1%) of HACO.

Conclusion
The incidence of CRE in Monroe County, NY has significantly increased since 2016 with documented emergence of blaNDM-producing strains. The high proportion of healthcare-associated CRE cases, particularly CP-CRE, underscores the need for enhanced infection control measures and ongoing surveillance. Further investigation is needed into the risk of CP-CRE in CA cases.

Disclosures
All Authors: No reported disclosures
P-1363. Cefiderocol Activity against Clinical Enterobacterales Isolates Carrying Metallo-β-lactamase Genes in United States and European Hospitals (2020–2023)
Authors: Mendes Rodrigo E , Kimbrough Hank , Beekman Danielle , Hubler Cory , Maher Joshua , Sader Helio S , Castanheira Mariana 
Published: January 2025

Abstract

Background
Cefiderocol (FDC) is a siderophore cephalosporin that uses the iron transport systems of Gram-negative bacteria to optimize cell entry. FDC is stable to hydrolysis by serine (e.g. ESBLs, KPC, and OXA-type carbapenemases) and metallo-β-lactamases (MBL). FDC and comparator activities were analyzed against Enterobacterales (ENT) carrying MBL genes, as part of the SENTRY Antimicrobial Surveillance Program.

Methods
32,052 ENT were collected from 35 sites in the US and 42 sites in the European (EU) regions during 2020–2023. Susceptibility (S) testing used broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB) for comparators and iron-depleted CAMHB for FDC. CLSI (same as the FDA) breakpoints were used for FDC; whereas CLSI were applied for comparators, except for colistin (EUCAST). ENT with MIC ≥2 mg/L (nonS based on CLSI criteria) for imipenem or meropenem were screened for β-lactamase genes.

Results
Carbapenem-nonS isolates comprised 2.9% (944/32,052) of the population, of which 1.4% (207/15,147) and 4.4% (737/16,905) originated from US and EU sites, respectively. FDC (94.6–96.6%S) had equivalent MIC90 of 4 mg/L against all carbapenem-nonS isolates, and the US and EU subsets, whereas other agents had S ≤86.5% (Table). FDC had MIC50/90 of 2/4 mg/L against isolates carrying MBL genes, including the blaNDM and blaVIM-1 subsets; in contrast, various other agents had off-scale MIC90 values (i.e. &gt;8 mg/L). FDC MIC90 of 8 mg/L were obtained against isolates carrying blaNDM-5.

Conclusion
FDC showed potent activity against carbapenem-nonS ENT and those subsets of isolates carrying MBL genes. This potent FDC activity is presented against a particular subset of resistant ENT, for which antibiotic treatment options are limited. FDC should be considered as an important option for the treatment of infections caused by these resistant organisms.

Disclosures
Rodrigo E. Mendes, PhD, GSK: Grant/Research Support
P-1366. Outcome of 10 Patients with Colistin-Resistant Gram-negative isolates in a Tertiary Care Hospital in South India
Authors: Shibi S , Shobana S , Sanjai R 
Published: January 2025

Abstract

Background
The emergence of colistin-resistant gram-negative isolates poses a significant challenge in the management of infections, particularly in tertiary care settings. This study aims to investigate the clinical outcomes of 10 patients with colistin-resistant gram-negative isolates in a South Indian tertiary care hospital. Understanding the impact of these resistant strains on patient outcomes is crucial for guiding treatment strategies and improving patient care in the face of increasing antimicrobial resistance.

Methods
This study conducted between January 2023-April 2024 at a tertiary hospital in India. We reviewed patients’ clinical profile, outcome, and antibiotics that were used for treatment.

Results
Ten colistin-resistant isolates were reported over 16 months. Respiratory was the most common source of the isolate, followed by blood and urine samples. Klebsiella pneumoniae constituted 50%, Acinetobacter baumannii 30%, Pseudomonas aeruginosa 20% of all isolates. Susceptibility of these isolates to other drugs were Amikacin 70%, tigecycline 58%, and chloramphenicol 25%. Antibiotics that were used for treatment combinations among the following antimicrobials as shown in Table 1.Table 1:Patient profile, antibiotic combination used, and outcomeS.NOSAMPLEANTIBIOTICS USED FOR TREATMENTOUTCOME1RespiratoryColistin +Tigecycline + ChloramphenicolDeath2RespiratoryMeropenem + ColistinDeath3RespiratoryCo-trimoxazole + TigecyclineDischarge4BloodTigecycline + ChloramphenicolDeath5PusAmikacin + ColistinDischarge6UrineChloramphenicol + ImipenemDischarge7RespiratoryColistin + TigecyclineDeath8RespiratoryAmikacin + ColistinDischarge9Wound SwabFosfomycin + ColistinDeath10RespiratoryMeropenem + ColistinDeath

Conclusion
Colistin resistance is becoming more common in Gram-negative bacteria, particularly K. pneumoniae, in Indian hospitals. Among patients infected with colistin-resistant gram-negative isolates, the mortality rate is 60%, while 40% are discharged. Amikacin, tigecycline, and chloramphenicol could be considered for combination therapy.

Disclosures
All Authors: No reported disclosures