bluuebunny/crossref_metadata_2025_split huggingface dataset:
P-1355. Trends in Carbapenemase and Co-carbapenemase Production among Enterobacterales in Latin America: SMART 2018-2022
Authors: Wise Mark G , Polis Thales , Siddiqui Fakhar , Young Katherine , Motyl Mary , Sahm Daniel F 
Published: January 2025

Abstract

Background
The proliferation of carbapenemases in many geographies has compromised the effectiveness of the carbapenem class of antimicrobials and constitutes a major clinical problem. However, carbapenems paired with β-lactamase inhibitors, like imipenem/relebactam (IMR), can restore their activity against isolates carrying some types of carbapenemases. We evaluated trends in carbapenemase and co-carbapenemase production among Enterobacterales collected as part of the SMART surveillance program in Latin America.

Methods
In 2018-2022, 47 clinical labs in 11 countries in Latin America (Argentina, Brazil, Chile, Colombia, Ecuador, Guatemala, Mexico, Panama, Peru, Puerto Rico, Venezuela) each collected up to 250 consecutive Gram-negative pathogens per year from patients with bloodstream, intraabdominal, respiratory tract, and urinary tract infections. MICs were determined using CLSI broth microdilution and interpreted with 2024 CLSI breakpoints. Most imipenem (IPM) nonsusceptible non-Morganellaceae Enterobacterales and ceftolozane/tazobactam (C/T) nonsusceptible Enterobacterales were screened for β-lactamases genes.

Results
Of the 29,419 Enterobacterales collected, 6669 tested non-susceptible to IPM or C/T; of these, 4474 (67.1%) were characterized molecularly. KPC was the most frequently observed carbapenemase each year, ranging from 40.8% of the characterized isolates in 2021 to 31.1% in 2022, exhibiting an overall slight decreasing trend (Fig. 1). In contrast, the rate of NDM detection increased annually, ranging from 2.0% of the characterized isolates in 2018 to 20.8% in 2022. Rates of detection of other carbapenemases, including OXA-48-like, VIM, IMP and GES remained low and relatively stable over the studied time frame. Detection of carbapenemase co-carriers peaked in 2021 (3.5%), with isolates harboring NDM & KPC the most common genotype (Fig. 2).

Conclusion
KPC was the most commonly encountered carbapenemase among Enterobacterales in Latin America from 2018-2022, suggesting agents that retain potency against KPC-carrying Enterobacterales, like IMR, remain appropriate therapies. However, the increasing trend of NDM detection in this region is of concern as it severely limits treatment options.

Disclosures
Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant
P-1358. Understanding Fungal Infections and Trends in Fungal Resistance: A Single Center Evaluation
Authors: Islam Nuzhat , Haste Nina , Kline Ahnika , Abeles Shira 
Published: January 2025

Abstract

Background
Invasive fungal infections cost the US health care system billions and are challenging to treat. In 2021 alone, the CDC estimates that fungal infections contributed to over $7 billion in direct medical costs and over 7,000 deaths in the US. The most common agents used to treat clinical fungal infections are azoles. However, antifungal resistance is on the rise. Exposure to agricultural fungicides has been identified as likely contributing to increased resistance to medical azoles, as there has been incidence of infection with azole-resistant fungi in patients who were azole-naïve. Furthermore, in vitro studies have demonstrated that fungi exposed to agricultural azoles develop cross-resistance to medical azoles. This study aims to describe retrospective antifungal susceptibility trends for medical azoles in patients at UCSD Health and agricultural azole use in San Diego and Imperial Counties.

Methods
Chart review was used to obtain sensitivity data (minimum inhibitory concentrations or MICs) for non-Candida fungal isolates sent for susceptibility testing from UCSD Health patients from January 2016 through February 2024. Data on fungal isolates including species, date of isolate collection, susceptibility data, and patient zip code were collected. Agricultural azole use data is publicly available from the California Department of Pesticide Regulation and was analyzed for azoles applied in San Diego and Imperial Counties from 2016 to 2021.

Results
189 fungal isolates from 170 patients were included in the analysis. Fusarium demonstrated high resistance to common medical azoles which did not change over time. A. fumigatus also exhibited minimal change in MICs for itraconazole and posaconazole but showed possible increase in MICs over time for voriconazole and isavuconazole. Imperial County had an 8 to 10-fold higher use of agricultural azoles compared to San Diego County.

Conclusion
Fusarium demonstrated resistance to all common medical azoles. There may be a possible increase in resistance of A. fumigatus to voriconazole and isavuconazole over time, however this is limited by small sample size. This study highlights the need for increased antifungal susceptibility testing at UCSD Health.

Disclosures
Nina Haste, PharmD, PhD, Novartis: Spouse is an employee
P-1369. Impact of the E152K Mutation in Resistance to Taniborbactam and Evolutionary Advantages of NDM-9
Authors: Vila Alejandro J , Delmonti juliana , Zuccato Francesco G , Pennesi Jazmin , Parodi Clarisa , Drusin Salvador I , Moreno Diego , Bonomo Robert A , Gonzalez Lisandro 
Published: January 2025

Abstract

Background
NDM is one of the most prevalent carbapenemases worldwide. Boronate-based inhibitors able to target Metallo−β-lactamases, MBLs, such as taniborbactam (TAN) and xeruborbactam (XER), are promising new drugs. However, NDM-9, the third most widespread variant of NDM-1 is refractory to the action of TAN. The E152K substitution in NDM-9 disrupts an attractive electrostatic interaction between the Glu residue in NDM-1 and the side chain of the inhibitor. We aimed to explore how the E152K was selected before the clinical use of TAN and its possible evolutionary pathways.
The C-terminal dynamics that tags protein degradation is quenched in apo-NDM-9
The C-terminal dynamics that tags protein degradation is quenched in apo-NDM-9

Methods
Minimum inhibitory concentrations of ceftazidime in Escherichia coli cells expressing NDM variants were determined in Luria Bertani (LB) media with increasing concentrations of dipicolinic acid (DPA). NDM-1 and NDM-9 were expressed in E. coli BL21(DE3) pLysS and purified by affinity chromatography. Site-directed mutagenesis was performed. Steady-state catalytic parameters were determined by initial rate measurements and/or by analysis of the progress curves, measured in HEPES buffer, pH 7.5 at 25°C. Deletion mutants in E. coli were obtained by CRISPR. NMR spectra were run in a 700 MHz Bruker spectrometer. Docking simulations were performed by using Glide.Figure 2.Protein levels in the periplasm of E. coli cells expressing different NDM variants as measured by immunoblotting upon zinc starvation.

Results
NDM-9 is able to confer higher resistance to ceftazidime than NDM-1 under zinc deprivation since apo-NDM-9 is more stable against the periplasmic proteases. NMR reveals that the C-terminal stretch recognized by the protease Prc is more rigid in apo-NDM-9, protecting this variant towards degradation. Despite this, E152K substitution is present only in NDM-9. We obtained new variants of more frequent substitutions such as M154L and A233V. The two double variants and the triple variant were generated. These combinations gave rise to NDM variant hyper-stable against degradation, which also showed resistance to TAN, as supported by docking experiments.

Conclusion
Resistance to TAN exhibited by NDM-9 is a secondary gain-of-function elicited by the E152K substitution, that represents a clinical threat since it stabilizes the protein under zinc limiting conditions. The finding of new combinations on the genetic background of NDM-9 giving resistance to TAN suggests that NDM-9 can further evolve by acquiring more mutations.

Disclosures
All Authors: No reported disclosures
P-1370. Molecular Bases and Mechanistic Insights of NDM-mediated Resistance to Cefiderocol
Authors: Vila Alejandro J , Warecki Brenda A , Mojica Maria F , Tomatis Pablo , Bethel Christopher , Rodriguez Magdalena , Ono Daisuke , Bahr Guillermo , Drusin Salvador I , Moreno Diego , Mahler Graciela , Bonomo Robert A 
Published: January 2025

Abstract

Background
Cefiderocol (FDC) is a novel cephalosporin with a siderophore-mimicking moiety that favors uptake into the periplasm through iron transporters. FDC was reported as the only cephalosporin refractory to hydrolysis by metallo-β-Lactamases (MBLs). However, resistance to FDC has been reported due to substitutions in the iron transporter coupled to the expression of the MBLs NDM-1 and NDM-5. In contrast, resistance emergence involving other MBLs such as VIM or IMP are not known. We aimed to identify the interaction of FDC with NDM and other MBLs.Table 1.Kinetic parameters of FDC hydrolysis by different MBLsNDM variants show considerable activity in FDC hydrolysis. In contrast, VIM-2 and IMP-1 show poor activity.

Methods
MICs values of FDC against Escherichia coli DH10B cells expressing different MBLs cloned into a pHSG298 vector were determined by the microdilution method in iron-depleted cation-adjusted Mueller-Hinton broth. NDM-1, NDM-5, IMP-1 and VIM-2 were expressed in E. coli BL21(DE3) pLysS and purified by affinity chromatography. Steady state catalytic parameters were determined by initial rate measurements measured in HEPES buffer, pH 7.5 at 25°C. NMR spectra were run in a 700 MHz Bruker spectrometer. Stopped-flow data were acquired in an Applied Photophysics spectrophotometer.
Mechanism of MBL-mediated resistance to FDC
Under high levels of NDM expression, the enzymatic activity counter the cefiderocol action, confering bacterial resistance against this antibiotic.

Results
MIC values of FDC in E. coli cells expressing NDM variants were 2 μg/ml, similar to NDM-1. Steady-state kinetic measurements showed that NDM-1 and NDM-5 hydrolyze FDC efficiently, with kcat/KM values of 1.9 and 1.2 x10^6 M-1s-1, respectively. In contrast, IMP-1 and VIM-2 displayed poor catalytic efficiencies (Table 1). Electrospray ionization mass spectrometry (ESI-MS) revealed that FDC forms an adduct with MBLs, which is significantly more stable in the case of IMP-1 and VIM-2. Stopped flow experiments under pre-steady state conditions show that both IMP-1 and VIM-2 form a stable adduct with FDC, that results in enzyme inhibition. Instead, NDM-1 is poorly inhibited since the formed adduct is less stable. NMR experiments confirmed the formation of an hydrolysis product and adduct.

Conclusion
Our results indicate that NDM-1 and NDM-5 hydrolyze FDC efficiently, in contrast to the poor activity of IMP-1 and VIM-2. These findings support the observation that clinical resistance is linked to overexpression of NDM variants and not to IMP-1 and VIM-2. This may guide the use of FDC against a specific group of MBLs and justifies pairing with an MBL inhibitor.

Disclosures
All Authors: No reported disclosures
P-1374. Syphilis in an American Indian Population: A Descriptive Analysis of Cases
Authors: Blair Andrea L , Comiford Ashley L , Mera Jorge 
Published: January 2025

Abstract

Background
Syphilis, a sexually transmitted infection, caused by the bacterium Treponema subspecies pallidum. Because of its numerous varied clinical presentations, it has earned the term "the great imitator and mimicker." Between 2017 and 2021, syphilis rates in the US increased by 72%, and Oklahoma cases increased by 223%. Further, American Indian/Alaska Natives (AI/AN) are disproportionately burdened by the increase in syphilis rates.
The objective of this presentation is to describe demographic characteristics of AI individuals diagnosed with syphilis between 2016 and 2023 within the Cherokee Nation Health Services (CNHS) system.

Methods
We extracted patient data collected through the CNHS electronic health record system. Individuals were included in this analysis if they had a positive syphilis result from January 1, 2016 through July 1, 2023. We analyzed the data using descriptive statistics including counts and percentages.

Results
Over the study period, 375 individuals were diagnosed with syphilis. The majority of individuals were 34 years or younger (61.5%), 50% of were female, 69.3% had a non-emergency or urgent care healthcare visit within the previous 12 months. About 45% had insurance, and 84% were single. Nearly 85% of individuals resided in a county with a Cherokee Nation clinic and 53.3% received treatment documented in the EHR. Most individuals were diagnosed during the COVID-19 pandemic (75.2%) and 45.1% were diagnosed through the emergency or urgent care departments. About 13% had a diagnosis of HCV, 30% had more than one other STI, and 16% of individuals received HIV PrEP treatment.

Conclusion
In the Cherokee Nation, syphilis primarily affects women of childbearing age, with a significant portion diagnosed in urgent care and emergency department settings, yet only 53% receive treatment. Investigating the reasons behind such low treatment rates and devising interventions to enhance them will be pivotal in curbing the surge in syphilis cases. Crucially, identifying demographic and other pertinent factors that could pinpoint those vulnerable to syphilis is imperative. Further research should concentrate on delineating risk factors for syphilis in this demographic and implementing preventive measures accordingly.

Disclosures
All Authors: No reported disclosures
P-1375. Evaluation of Comprehensive STI Screening in the Emergency Department Setting
Authors: Sciarra Braden , Frasca Katherine , Montague Brian T 
Published: January 2025

Abstract

Background
Sexually transmitted infections (STI) are a common reason for emergency department (ED) evaluation. Patients diagnosed with or suspected to have an STI are also at risk for other STIs, and should be screened in accordance with Center for Disease Control (CDC) recommendations.Figure 1:Percentage of HIV screenings among ED patients tested for STIs

Methods
This study is a retrospective analysis of comprehensive STI screening conducted at eleven freestanding emergency departments associated with an academic referral center. Individuals tested for gonorrhea, chlamydia, and syphilis between 1/1/2019 and 12/31/2023 in the emergency department were evaluated for the completion of appropriate comprehensive STI screening, defined as the completion of HIV co-testing during the same ED encounter. Additional evaluation of HIV testing was also completed in higher risk individuals that tested positive for gonorrhea and/or chlamydia.Figure 2:Percentage of HIV screenings among ED patients testing positive for gonorrhea or chlamydia

Results
The analysis showed that comprehensive STI screening in the emergency department was completed in only 2.9% of the 10,895 patients that were screened for gonorrhea, chlamydia, or syphilis. The rate of comprehensive STI screening in the emergency department was 2.6% among the 2,082 patients that tested positive for gonorrhea and/or chlamydia.

Conclusion
The CDC recommends HIV screening for all persons that present for evaluation of possible sexually transmitted infections. Our analysis of individuals undergoing STI screening in the ED demonstrates a significant gap in HIV screening, including amongst higher risk individuals that have tested positive for gonorrhea and/or chlamydia. Based on these results, a comprehensive STI screening educational tool was developed within the electronic medical record to increase comprehensive STI screening. Further analysis of these interventions will be studied in the future.

Disclosures
Brian T. Montague, DO MS MPH, Regeneron: Grant/Research Support
P-1423. Barriers to Care: Improving Outpatient Follow-Up for Patients on Long-Term Oral Antimicrobial Therapies
Authors: Cummins Heather , Benefield Russell J , Certain Laura 
Published: January 2025

Abstract

Background
Best practice for patients on COpAT (Complex Outpatient Antimicrobial Therapy) includes close follow-up once discharged from the hospital. However, some patients discharged with COpAT do not receive monitoring for complications, increasing their risk for re-admission. There is limited analysis regarding patient-specific social determinants of health (SDOH) that may contribute to a reduced follow-up rate. We aimed to determine the percentage of patients discharged on long-term oral antibiotics who received recommended outpatient Infectious Disease (ID) support and potential barriers to follow-up for quality improvement.Table 1:Outcomes associated with social determinants of healthSelected social determinants of health associated with specified monitoring and outcomes. Bolded values are considered statistically significant.

Methods
In this single-center cohort, patients discharged between 1/1/2021 and 12/31/2022, on ≥ 2 weeks of oral antibiotics, age &gt; 18 years, with inpatient ID consult, and with recommendations for follow-up in the University of Utah ID Clinic were examined. SDOH included distance from the medical center, age, race/ethnicity, employment status, substance use, homelessness, and history of bipolar disorder/psychoses. We assessed patient outcomes of treatment failure or lost to follow-up within 90 days post-discharge. We also evaluated the time to appointment, lab monitoring, and number of adverse drug events (ADEs) after discharge.

Results
One hundred ninety-seven patients met the inclusion criteria for the cohort. Median times to suggested lab monitoring and ID appointment were 13 and 21 days post-discharge respectively. 71% completed lab monitoring within 90 days of discharge. After 90 days, 19% of patients were lost to follow up and 20% had experienced treatment failure. Those younger than 55, unemployed, or experiencing substance use were more often lost to follow-up. Individuals with substance use or age &lt; 55 had a longer time to lab monitoring. Patients with a history of substance use had fewer ADEs (Table 1).

Conclusion
SDOH that contribute to patient outcomes include a history of substance use and unemployment, suggesting an area of clinical quality improvement. Additionally, those younger than 55 were more often lost to follow-up. Further examination of follow-up protocol for these patients is important to improve patient outcomes.

Disclosures
Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support Laura Certain, MD, PhD, Zimmer Biomet: Advisor/Consultant
P-1425. Paxlovid Utilization and Social Vulnerability: Trends in Connecticut from 2022-2023
Authors: Hohenstein Laura , Maloney Meghan , Banach David 
Published: January 2025

Abstract

Background
The COVID-19 burden disproportionately affects communities with lower socioeconomic status and high social vulnerability, as well as minority racial groups. Disparities have also been described in nirmatrelvir/ritonavir (Paxlovid) prescription rates across socioeconomic strata.
Differences in nirmatrelvir-ritonavir dispensing rates between SVI quartile groups from March 2022 – February 2023

Methods
We performed an ecological analysis of associations between CDC social vulnerability index (SVI) and nirmatrelvir-ritonavir dispensing rates in Connecticut census tracts. SVI was categorized in four quartiles (low, low-medium, medium-high, and high). Nirmatrelvir/ritonavir dispensing locations were geocoded and dispensing rates per 1,000 population were calculated as the sum of courses dispensed per census tract during March 2022–February 2023. Independent-T tests were used to compare SVI in census tracts with and without medication dispensing sites. ANOVA with Tukey’s test was used to identify differences in dispensing rates by SVI quartile with paired t-test to identify significant differences before and after availability of the bivalent COVID-19 booster vaccine (March–August 2022 vs. September 2022–February 2023).
Demographic and COVID-19 characteristics of census tracts with and without a nirmatrelvir/ritonavir dispensing site

Results
Mean SVI was higher in 367 census tracts with a dispensing site (mean 0.56) compared to 506 census tracts without a dispensing site (mean 0.45) (p &lt; 0.01). Nirmatrelvir/ritonavir dispensing rates were lower in census tracts with high SVI (55.9 courses per 1000 people) compared to census tracts with low-medium SVI (93.1; difference -37.2 95% confidence interval (CI) [-68.5, -5.9]) and census tracts with medium-high SVI (96.6; difference -40.7, 95% CI [-69.9, -11.5]). Dispensing rates were higher after availability of the bivalent COVID-19 booster vaccine compared to before (p &lt; 0.05), except in census tracts with high SVI where there was no statistically significant difference.
Nirmatrelvir/ritonavir dispensing rates per 1,000 population by census tract SVI quartile before and after availability of the bivalent COVID-19 booster vaccine

Conclusion
Census tracts with high social vulnerability were less likely to have a dispensing site and had lower nirmatrelvir/ritonavir dispensing rates per 1,000 population. Observed differences in dispensing might signify inequities in healthcare access or medication prescribing. Findings highlight the importance of understanding and addressing barriers to accessing therapeutics in high vulnerability areas during public health emergencies.

Disclosures
Meghan Maloney, MPH, Pfizer Global R&D: Former employee, separated in 2009. I do have a retirement entitlement which I do not actively manage/no stock options. PGRD offers periodic buy outs
P-1451. Missed Opportunities for HIV Diagnosis in Mexico City: Unveiling the Gender Gap
Authors: Sierra-Barajas Nancy , Caro-Vega Yanink , Sierra-Madero Juan G , Benavides Rodrigo Ville , López-Iñiguez Alvaro , Mejia-Castrejon Jessica , Juarez-Campos Karen , Silva-Casarrubias Angelina , Crabtree-Ramírez Brenda 
Published: January 2025

Abstract

Background
Women in Mexico are not considered a key population for acquiring HIV, consequently, neither the patients nor their physicians are aware of this risk. This lack of recognition may contribute to late diagnoses and unfavorable clinical outcomes. This study aims to determine the frequency of missed opportunities for HIV diagnosis (MOHD) in a tertiary care center in Mexico City.

Methods
A questionnaire for newly enrolled healthcare patients was routinely applied since 2013 to look for MOHD, at the HIV Clinic of a tertiary care center in Mexico City. MOHD was defined as a healthcare encounter in which a) HIV diagnosis was not made, b) was prompted by a clinical manifestation related to HIV, and c) occurred at least 30 days before the HIV diagnosis was confirmed. Frequency and proportion of MOHD by sex were reported, we described demographics, presence of AIDS at enrollment and compared the proportion of MOHD and AIDS defining events by gender.

Results
A total of 1,143 questionaries were applied from January 1st 2013, to December 31st 2023; 107 (9.4%) respondents were female and 1036 (90.6%) were male. A total of 486 (42.5%) patients reported experiencing symptoms related to HIV before their diagnosis, with 36 (7.4%) being women. 466 of 486 sought medical attention for their symptoms: 403 patients had data to establish MOHD, 27 were women and 376 men. MOHD was considered in 18/27 (66%) women and in 155/376 (41%) men (p=0.03). Among the patients with MOHD, 10/18 (56%) of the women and 52/155 (34%) of men had AIDS at enrollment in HIV care (p=0.02).
In the MOHD group, women's mean age was 43 years (SD=12.2) vs 35 in men (SD=12.2, p=0.01), 39% were married (7/18) vs. 11% of the men (17/155) (p&lt; 0.01), and years of education were similar: 12.2 (SD= 4.6) vs. 13.2 (SD=4.2), respectively (p=0.51).

Conclusion
This study reveals a higher proportion of missed opportunities for HIV diagnosis and AIDS in women compared to men. Women with MOHD were older and married in a higher proportion than men. Our results underscore the urgent need of strategies for increasing awareness of HIV risk in Mexican women.

Disclosures
All Authors: No reported disclosures