bluuebunny/crossref_metadata_2025 huggingface dataset:
P-1323. Forecasting the incidence of acute respiratory infections in Uzbekistan, 2022-2023
Authors: Ibragimov Rafail , Nabirova Dilyara , Horth Roberta , Kurbanov Botirjon
Published: January 2025

Background

Acute respiratory infections (ARIs) are a significant cause of morbidity and mortality worldwide, and this is particularly evident in regions such as Uzbekistan within Central Asia. Forecasting ARIs allows public health authorities to anticipate and prepare for surges in cases. This includes ensuring that healthcare facilities have adequate resources, such as hospital beds, ventilators, medicines, and personal protective equipment (PPE). Therefore, we aimed to predict the incidence of ARIs in Uzbekistan and respond to public health threats in a timely and appropriate manner.Figure 1.Short-term prediction of incidence acute respiratory infections in Uzbekistan, 2022-2023

Methods

We conducted a retrospective study using weekly data on the incidence of ARIs reported in Uzbekistan between January 2022 and November 2023. Two models were selected to predict the number of ARIs cases. The first model, based on prediction using the EpiNow2 package, was used for short-term prediction for 2 weeks, and the second model, from the nnetar package, based on neural networks for prediction of univariate time series, was used for prediction for the next 12 weeks. Data analysis was performed in R version 4.3.2.Figure 2.Long term prediction of incidence acute respiratory infections in Uzbekistan, 2022-2023

Results

The short-term forecast for the following 2 weeks showed a possible increase in case numbers (rate of growth = 0.011 (95% CI 0.004 - 0.028)). The model predicts 2,310 (767 - 2,939) new cases by infection date. At the end of the forecast period, the model predicted 5,711 (2,486 - 39,623) new cases of ARIs per week . The long-term model predicted 217,469 (176,261 - 247,929) new infections over the next 12 weeks. At the same time, the peak incidence was predicted to occur in December 2023. In that month, the model predicted 19,817 (17,340 - 22,303) new infections per week. When evaluating the accuracy of the model, we found that the predicted values were lower than the actual number of cases (mean absolute percentage error (MAPE) of the first model = 0.68, MAPE of the second model = 0.39).

Conclusion

The selected models of forecasting make it possible to determine the possible number of cases, although they underestimate values of these cases. The country needs to collect data on risk factors to better predict the incidence of ARIs. However, short- and long-term forecasting models can help to adjust public health response.

Disclosures

All Authors: No reported disclosures
P-1326. Trends in Transgender Sexual Health: New Findings from Syphilis Cases
Authors: Geher Sage W R , Spivak Adam , Sullivan Erika A , Ho Tiffany F
Published: January 2025

Background

Syphilis has been on an alarming rise with worldwide cases in excess of 7 million in 2020 and US case rates tripling over the last 20 years. Sexually transmitted infections disproportionally impact sexually minoritized groups, including transgender and gender diverse (TGD) adults. Yet, syphilis rates among TGD people are relatively understudied. We sought to investigate syphilis trends specifically in the TGD community.

Methods

We performed a retrospective chart review and identified 33 TGD adults diagnosed with syphilis, from a total cohort population of 1,072 transgender persons tested for syphilis from 2010-2023. Persons diagnosed with syphilis were identified by one of the following criteria: International Classification of Diseases-10 (ICD) code, positive treponemal test (Tp), or positive non-treponemal test (NT). Diagnoses were further delineated into individual cases of syphilis to account for re-infections. True cases were defined as having positive Tp and NT, presumed positive as positive Tp or NT, and false positives as having a negative Tp or NT. Variables such as syphilis incidence and prevalence were calculated. Various qualitative aspects of disease progression and case presentation were analyzed via manual chart review.

Results

We identified 22 true cases, 8 presumed positives, and 12 false positives. Syphilis incidence was 2.79% and lifetime prevalence of 1.95%. While the number of syphilis tests increased per year, test positivity rates remained fairly constant at 3-4%. The vast majority of cases presented as primary syphilis (72%), and were most often completely asymptomatic (59%), with chancre (24%) and unexplained headache (14%) being the most common symptoms across all stages. There was only one case (3%) of confirmed neurosyphilis, which is higher than the national incidence (0.8-1.7%). Titers at time of diagnosis spanned a large range of values and was not predictive of stage of presentation, nor was there a clear correlation in titer kinetics and response to treatment.

Conclusion

With a relative paucity of investigations looking at syphilis rates in the TGD community, especially in the United States, understanding the epidemiology of this population could prove critical in prevention efforts.

Disclosures

All Authors: No reported disclosures
P-1328. Contribution of Antimicrobial Resistance Data of NARMS Retail Meat in the Investigation of Persistent Strain of Salmonella Hadar Infections, Tennessee, 2021-2023
Authors: Hanna Samir , Garman Katie , Dunn John R
Published: January 2025

Background

Reoccurring, Emerging, and Persisting (REP) strains of Salmonella have caused illness for several years and are linked to multiple sources. Some REP isolates have been detected in food products like MDR Salmonella Infantis (REPJFX01) in retail chicken. Tennessee participates in the FDA’s National Antimicrobial Resistance Monitoring System (NARMS) Retail Meat Surveillance to monitor the antimicrobial resistance of retail meat enteric bacteria isolates. We reviewed the contribution of TN NARMS data in the investigations of multistate (MS) outbreaks caused by persistent strain of S. Hadar (REPTDK01).

Methods

Tennessee submits every 20thSalmonella isolates from humans statewide, and all Salmonella isolates from retail meat (retail chicken, ground turkey, ground beef and pork products) purchased from 13 counties to NARMS. Sequenced isolates are uploaded to PulseNet, and resistance determinants are monitored. TN responds to CDC/FDA requests on isolates with persisting strains matching MS outbreaks.

Results

REPTDK01 strain was detected in 4 ground turkey (GT) isolates from TN as part of 2 multistate outbreaks in 2021 (2102MLTDK-1) and 2023 (2302MLTDK-1). Over 95% of human and non-human isolates in both outbreaks were resistant to tetracycline, streptomycin, or both, and 0.2-0.4 % to ciprofloxacin and ceftriaxone respectively. Three of the 4 GT samples were purchased from grocery stores in different counties in 2021, and two of them had the same producer establishment number. USDA issued a public health consumer alert for over 211,406 pounds of raw GT products produced by the establishment. An additional GT sample was purchased in 2023 with a different establishment number. Consumption of GT was reported by 20 (60%) of 33 cases in 2021, while no signal of GT consumption among 55 cases in 2023. TN had no human cases in both outbreaks. However, a total of 49 cases from TN were linked to another three MS outbreaks of REPTDK01 associated with backyard poultry contact between 2019 and 2023 with one death in 2022.

Conclusion

NARMS retail meat routine surveillance data contributes to a better understanding of source attributions of REP bacterial strains. Sharing of TN data with federal partners helped in traceback efforts, regulatory actions, and alerting the public.

Disclosures

All Authors: No reported disclosures
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
Authors: Kumar Deepak , Khandelwal Lochan , Bohra Gopal Krishna , Tak Vibhor , Meena Durga Shankar , Midha Naresh Kumar , Garg M K , Jain Vidhi , Choudhary Gautam Ram
Published: January 2025

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-1388. Repeat Trichomonas vaginalis Infections Among Pregnant Women in South Africa
Authors: Lim Lindsay S , Mdingi Mandisa , Mukomana Freedom , Gigi Ranjana M S , Low Nicola , Peters Remco , Medina-Marino Andrew , Klausner Jeffrey , Muzny Christina A
Published: January 2025

Background

Trichomonas vaginalis (TV) is the most common non-viral sexually transmitted infection (STI) worldwide. It has been associated with multiple adverse outcomes in pregnancy. The prevalence of repeat TV infections among pregnant women is poorly characterized, especially in resource-limited countries. This study aimed to investigate the prevalence and causes of repeat TV infections in pregnant women in South Africa.

Methods

Women enrolled in a randomized controlled trial investigating optimal STI screening strategies during pregnancy were included. At baseline, TV was diagnosed via the GeneXpert nucleic acid amplification test (NAAT). Demographics, sexual history, and partner characteristics were collected. If positive, women were treated with multi-dose oral metronidazole and randomized to Arm 1 or 2 (test-of-cure at 3 weeks after enrollment or re-testing at 32-34 weeks gestation). At follow-up in both arms, a repeat TV NAAT was obtained and a questionnaire was administered examining adherence to treatment, partner treatment history, and interval sexual activity. Women with confirmed treatment completion and a repeat positive TV NAAT were classified as treatment failure if no interval sexual activity, re-infection if had interval sexual exposure to baseline partners who were not treated as contacts, or new infection if exposed to a new partner.

Results

Baseline TV prevalence was 10% (144/1440) (Figure 1) and 10.4% (15/144) of infected women had a repeat positive test with baseline characteristics shown in Table 1. All 15 women finished their entire course of treatment and partners were notified in 93.3% of cases (Table 2). Based on our definitions, 60% of women (9/15) were classified as treatment failure in the setting of no interval sexual exposure or sexual exposure with partner who was reportedly treated (Figure 2). 26.7% (4/15) were classified as re-infection and 13.3% (2/15) were unable to be classified. There were no new infections.

Conclusion

More than half of repeat TV infections in this cohort of pregnant women in South Africa were determined to be due to treatment failure. Additional studies with larger sample sizes are needed to further investigate potential causes and include drug susceptibility testing on clinical TV isolates in women with repeat infections.

Disclosures

Jeffrey Klausner, MD MPH, Direct Diagnostics: Advisor/Consultant Christina A. Muzny, MD, MSPH, Abbott: Advisor/Consultant|Abbott: Grant/Research Support|BioMed Diagnostics: Advisor/Consultant|BioNTech: Advisor/Consultant|BioNTech: Grant/Research Support|Cepheid: Advisor/Consultant|Cepheid: Honoraria|Elsevier: Honoraria|Gilead: Grant/Research Support|Lupin Pharmaceuticals: Grant/Research Support|Merck Manuals: Board Member|Merck Manuals: Honoraria|UpToDate: Honoraria|Visby: Grant/Research Support
P-1408. Beyond the Transplant: Understanding CMV Disease in Minority Kidney Recipients
Authors: Gabriela Cabanilla M , Dauenhauer Ashlee , John Briana St , Pham Ngoc-Yen , Hill Deirdre , Larson Joshua , Singh Pooja P
Published: January 2025

Background

Disparities in kidney transplant evaluation for minorities raise concerns about post-transplant care access, including cytomegalovirus (CMV) infections and their impact. While CMV significantly affects morbidity and mortality rates, the precise ramifications of these disparities remain unclear. We aimed to evaluate CMV infection patterns in minority kidney transplant recipients.

Methods

We evaluated CMV infection in minority kidney transplant recipients using retrospective analysis and qualitative surveys. Patients aged ≥ 18 years with post-transplant CMV infection were included. Data were collected from University of New Mexico Health Sciences Center records and provider surveys. The primary outcome was CMV disease incidence among minority populations, with secondary outcomes exploring clinical endpoints and barriers to CMV management. Quantitative and qualitative data were analyzed using descriptive statistics, chi-square and Fisher’s exact tests, and thematic analysis.

Results

Among 58 patients (84.5% minorities), CMV disease cumulative incidence was 12.3% in minorities vs. 0% in non-Hispanic whites (p = 0.58), despite similar prophylaxis. No significant CMV disease risk factors were found. Graft failure occurred in 8.6% of patients, mostly minorities, with one graft loss after CMV diagnosis. Mortality appeared higher in minorities (24.4% vs 11.1%, p = 0.67), especially within 90 days of CMV diagnosis, and notably elevated in diabetics (40% vs 9.1%, p = 0.01).

Eight respondents (75% transplant specialists) highlighted CMV management challenges from diagnosis to resource access. Providers acknowledged limitations in current strategies and expressed optimism for newer therapies, such as letermovir. Systematic barriers, including policy gaps and suboptimal multidisciplinary collaboration, were identified as hindrances to comprehensive care delivery.

Conclusion

Our study underscores the CMV disease burden among minority kidney transplant recipients, highlighting disparities in incidence and clinical outcomes compared to non-Hispanic whites. Urgent interventions and policy reforms are required to address systemic barriers and improve post-transplant care equity, ultimately enhancing the health outcomes of minority transplant patients.

Disclosures

M. Gabriela Cabanilla, PharmD, PhC, Merck & Co: Grant/Research Support
P-1410. Oral Antimicrobial Therapy Offers in Hospitalized Persons Who Inject Drugs who Elect for Self-directed Discharge
Authors: Arena Christen J , Vanhorn Bryce , Kenney Rachel M , Parke Dana M , Suleyman Geehan , Davis Susan L , Veve Michael
Published: January 2025

Background

Hospitalized Persons Who Inject Drugs (PWID) who elect for self-directed discharge (SDD) are at an increased risk for poor infection outcomes, but there is limited guidance for infection management in this population. National PWID management guidelines suggest considering oral antimicrobial therapy offers (OATO) as soon as patients are clinically stable to avoid lack of antibiotic therapy at discharge. The study purpose is to evaluate infection management in PWID who elect for SDD and to identify characteristics associated with OATO.

Variables Associated with Oral Antimicrobial Offers at Self-directed Discharge

Methods

Retrospective cohort of hospitalized adult PWID with an injection drug use (IDU)-related infection who elected for SDD between 1/1/14-1/31/24 at Henry Ford Health in Michigan. Patients were excluded if they were hospitalized for < 24-hours or if antimicrobial treatment was completed prior to SDD. The primary outcome was the proportion of patients with OATO at or prior to SDD. Secondary outcomes at 30-days included retreatment, infection-related readmission, and all-cause mortality.

Results

150 patients were included; 55 (37%) were OATO patients, 95 (63%) did not receive an offer. Most patients were white (118, 79%), had prior SDD (90, 60%), and were a median (IQR) age of 34 (30-44) years. Skin infections were most common (81, 54%). Patients that received a source control procedure (27 (49%) vs. 31 (33%), P=0.05) or care from a provider ≤10 years from terminal training (49 [89%] vs. 70 [74%], P=0.04) were more likely to receive an OATO. Patient outcomes were not different between the OATO and no offer groups: infection retreatment 19 (34%) vs. 32 (34%); infection-related readmission 14 (25%) vs. 31 (33%); and all-cause mortality 1 (2%) vs. 3 (3%). Characteristics associated with OATO were prescribing or continuing medications for opioid use disorder during hospitalization, infection source control, and care from providers ≤10 years post-terminal training; infectious diseases consultation had an opposite association (Table 1).

Conclusion

Most hospitalized PWID with IDU-related infections with SDD did not receive an OATO. Early career providers more commonly offered oral antimicrobials in PWID with less complicated infection types. Standardizing OATO in PWID at risk for SDD should be considered as a future direction to improve health outcomes.

Disclosures

Rachel M. Kenney, PharmD, BCIDP, Medtronic Inc: Spouse is an employee, stockholder Dana M. Parke, MA, Pfizer Global Medical Grants & Global Bridges at Mayo Clinic (grant # 70973735): Grant/Research Support|The Kresge Foundation: Grant/Research Support
P-1411. Perinatal Care-Seeking Among Women Living with HIV in Uganda
Authors: Alperin Cora , Atukunda Esther , Harper Cynthia , Baguma Charles , Kembabazi Annet , El Ayadi Alison , Mushavi Rumbidzai , Satinsky Emily , Juliet Mercy , Betty Namara E , Ahereza Phionah , Tsai Alexander , Comfort Alison
Published: January 2025

Background

Inadequate perinatal care uptake in Uganda, as outlined by national guidelines (eight antenatal visits starting before 26 weeks, supervised facility delivery, and at least one postnatal checkup), persists as a significant issue. Factors such as HIV-related stigma further hinder healthcare engagement during this period. This study evaluates differences in antenatal and postnatal care-seeking between women living with HIV (WLHIV) and HIV-negative women in Uganda.

Methods

We performed a cross-sectional study of women 18 years and older (n = 417) living in Nyakabare parish, Southwestern Uganda. The study sample was part of a longitudinal complete population cohort followed since 2014. We collected survey data on care-seeking at most recent pregnancy, including self-reported HIV status and HIV testing, timing of perinatal care, and socio-demographics. Outcomes of interest included antenatal care access (ANC), timing of ANC initiation, ANC visits, and postnatal care (PNC) access. The primary explanatory variable was self-reported HIV status. Analyses were conducted using a binomial logistic regression model with covariate adjustment for age, education, wealth, and village.

Results

On average, women initiated ANC in the second trimester when 4 months pregnant, much later than recommended. Further, women attended half the number of recommended ANC visits (4 of 8 visits). Most women (87%) delivered in a healthcare facility and accessed ANC (98%). There was no significant difference in ANC access, time of initiation of ANC, frequency of ANC visits, or location of delivery by HIV status. WLHIV were 2.6 times more likely to have had a postnatal care visit (adjusted odds ratio [aOR] 2.6, 95% confidence interval [CI]1.1-5.5). 68% of WLHIV sought PNC compared to 40% of women who were HIV-negative.

Conclusion

The data reveal a trend of late ANC initiation and incomplete care among all women regardless of serostatus. However, WLHIV were more likely to access PNC compared to HIV-negative women, potentially indicating effective support and follow-up once initiating ANC. Research exploring why WLHIV more consistently access PNC is needed. Targeted interventions to ensure earlier ANC initiation, including for WLHIV, are crucial and should consider differences in healthcare system engagement.

Disclosures

All Authors: No reported disclosures
P-1414. An Analysis of Social and Clinical Characteristics of Individuals who Acquired a Central Line Associated Bloodstream Infection (CLABSI)
Authors: Schocken Derek D , Kim Mindy , Gettler Erin , Okeke Nwora Lance , Turner Nicholas A , Anderson Deverick J
Published: January 2025

Background

A previous exploratory analysis of surveillance data at our large academic medical center identified higher CLABSI rates among non-Hispanic Black patients compared to White patients. In the context of a growing understanding of the importance of social determinants of health (SDOH), we sought to better describe those patients who acquired a CLABSI.

Methods

We conducted a retrospective analysis of patients with CLABSI who were admitted to one of 3 hospitals in our health system in 2022 (1 large academic and 2 community hospitals). CLABSI was defined using standard NHSN criteria. We compared demographic, admission, clinical and SDOH data between patients identifying as White or non-Hispanic Black. These groups were selected due to sample size limitations. Race was defined based on information from the EHR. To identify variables associated with race that may mediate differences in acquiring CLABSI, we created a logistic regression model using stepwise backwards selection.

Results

Among 167 patients with CLABSI, 86 (52%) identified as White and 67 (40%) identified as Black. Social and clinical characteristics of the cohort are included in Table 1. Data on central lines in place at diagnosis are included in Table 2. The 3 most common organisms were Staphylococcus epidermidis, S. aureus, and Pseudomonas aeruginosa. Median Elixhauser scores were not different between groups (9 v. 10, p = 0.2). Median Social Deprivation Index also did not differ between groups (64 v. 66, p = 0.4). Clinical and social characteristics identified via logistic regression as independently associated with race are described in Table 3.

Conclusion

Black patients with CLABSI more frequently required assistance in their ADLs, more frequently had a line dedicated to dialysis, and were less likely to have psychosocial concerns identified or documented. The results of this analysis support the complex interrelated nature of biopsychosocial factors that may predispose to disparate needs for central venous catheters and therefore inequities in the risk of CLABSI. Additionally, disparities in screening and documentation of SDOH exist in this cohort. Future studies should aim to quantify the risk of acquiring a CLABSI conferred by race.

Disclosures

Nicholas A. Turner, MD, MHSc, PDI: Research contract|Purio Labs: Research contract
P-1418. Risk for Early and Late Readmission for Serious Injection-Related Infections: the CHOICE+ Cohort
Authors: Traver Edward C , Omari Habib , Stevens Jasmine , Derenoncourt Meghan , Flores Hannah E , Vaish Ishan Kumar , Raman Sumitha , Fujita Ayako Wendy , Reece Becky , Kuo Irene , Steck Alaina , Catalanotti Jillian S , Carpenter Joseph E , Kattakuzhy Sarah , Rosenthal Elana S
Published: January 2025

Background

People who inject drugs hospitalized with severe injection-related infections (SIRI) face barriers to antibiotic treatment completion and remain at risk for new infections due to ongoing injection drug use. We explored risk factors for SIRI readmission and whether readmissions were caused by the index SIRI or a new SIRI.

Methods

CHOICE+ is a retrospective cohort study of adults hospitalized with SIRI due to injection opioid use at 4 hospital systems between 1/1/2018 and 3/31/2022. Data were collected by abstraction of the medical record. Primary outcomes were readmission for SIRI within 1 year and time to readmission. Categorical variables were analyzed by chi-square, Fischer exact test, and multivariate logistic regression. Time to readmission was compared by the Mann-Whitney test.

Results

Of 1618 patients discharged alive, 439 (27%) had ≥1 readmission for SIRI. Unstable housing, patient-directed discharge, and not finishing planned intravenous antibiotics in the hospital were associated with increased risk for SIRI readmission (Table 2). Risk of SIRI readmission was not associated with addiction or psychiatry consultation, discharge on medication for opioid use disorder (MOUD), or type of MOUD. The cause of readmission in 238 (54%) was the index SIRI and in 201 (46%) was a new SIRI. Median time to readmission was shorter for those readmitted with index SIRI compared to a new SIRI (10 v. 126 days, p < 0.0001, Figure 1) and for those who did not complete treatment for the index SIRI compared to those who completed treatment (7 v. 78 days, p < 0.0001, Figure 2).

Conclusion

In this large, representative study, readmission for SIRI occurred frequently for both problems related to the index SIRI as well as development of new SIRI. Readmission for index SIRI occurred earlier than for new SIRI, especially for those who did not complete antibiotic treatment. Notably, readmission for SIRI was not associated with inpatient interventions to address addiction during the index hospitalization. Therefore, prioritizing completion of treatment of the index SIRI may be critical for reducing early readmissions. In contrast, prevention of new SIRI, by longitudinally addressing addiction, social determinants of health, and harm reduction, may be necessary to reduce later readmissions.

Disclosures

Elana S. Rosenthal, MD, Gilead Sciences: Grant/Research Support|Merck: Grant/Research Support
P-1427. Continuation of HIV and hepatitis C care among refugees migrating from Ukraine - Five Times Ninety project
Authors: Kowalska Justyna , Antoniak Sergii , Samsonova Olena
Published: January 2025

Background

Five Times Ninety project investigates linkage to care among war refugees living with HIV displaced from Ukraine to Poland.Figure 1.Gender and mode of HIV infection of Ukrainian refugees stratified by time of registering to care in Warsaw

Methods

Refugees who registered to HIV care in Warsaw were followed according to “Standardized protocol for clinical management and medical data sharing for PLHIV among refugees from Ukraine” developed by WHO/CHIP,EACS, ECEE and ECDC (https://iris.who.int/handle/10665/353083). For each patient who signed informed request data were linked to database at the Public Health Center (PHC) Ministry of Health Ukraine, and sent back on standardized form.Figure 2.Cascade of HIV care of Ukrainian refugees registered to care in Warsaw

Results

Among 205 refugees who registered to HIV care in Warsaw (5 Mar2022 - 31Aug2023) 202 (98.7%) were linked with PHC database, 121 (59.9%) were female, median age 40.0 (range 18-69, IQR 36.0-46.0), migrating from Central (67; 33.2%), South (65; 32.2%), East (39; 19.3%), West (27; 13.4%) and North (4; 2.0%) Ukraine. Mode of HIV infection was heterosexual in 113 (55.9%), other/unknown in 51 (25.2%), injecting drug use in 28 (13.9%) and MSM in 10 (4.9%) persons. Women and persons who acquired HIV through heterosexual contacts were more likely to migrate earlier, but age structure did not significantly change over time (Figure 1). On 31Dec2023 in total 128 (63.4%) patients remained in care in Warsaw.

189 patients (93.1%) had HIV viral load measured both in Ukraine and Poland, 173 (91.5%) and 155 (82.0%) were undetectable, respectively. This translates into 9.5% loss of ART efficacy during a transition period. These improved over time (Figure 1). Switching of antiretroviral therapy occurred often, yet majority remained on integrase inhibitor (194; 98.0%) and tenofovir (176; 88.9%), Figure 4.

148 persons (73.6%) were tested with HCV serology in Ukraine and 187 (93.0%) in Poland. Of 59 (31.5%) tested positive in Poland, 24 were post-DAA therapy in Ukraine. Of 35 who were tested with PCR in Poland, 10 had undetectable HCV RNA, 25 had detectable HCV RNA of whom 10 already went through DAA therapy, Figure 3.Figure 3.HCV testing and treatment for Ukrainian refugees registered to care in Warsaw

Conclusion

Standardized protocol proved to be an efficient for medical data exchange. Viral suppression among Ukrainian refugees on ART decreased slightly, but in general remained high and improved with time. Routine HCV screening is a necessity, especially because there are no restrains to DAA treatment access in Poland.Figure 4.Antiretroviral therapy switches among refugees registered to care in Warsaw

Disclosures

All Authors: No reported disclosures
P-1429. Racial Disparities in Childhood Vaccination Rates and Their Association with State-Level Structural Racism
Authors: Han Jin-Young , Wu Yiyuan , Abramson Erika
Published: January 2025

Background

Racial disparities in childhood vaccination rates are well-documented nationally. These disparities may vary across states due to multiple reasons, including vaccine exemptions. A structural racism score is a measure developed to quantify systemic racial disparities across various domains, including segregation, economic status, and incarceration. Notably, structural racism is more pronounced in Northeastern and Midwestern states of the United States. Leveraging recently published Black structural racism scores at the state level, we examined the relationship between structural racism and childhood vaccination rates among non-Hispanic Black and non-Hispanic White children.

Methods

We analyzed 5-year aggregate vaccination rates (2017-2022) for children aged 19-35 months using data from the US Centers for Disease Control and Prevention National Immunization Survey-Child (NIS-Child). The main outcome was the difference in percentage points between non-Hispanic Black and non-Hispanic White childhood vaccination rates for each state. The childhood vaccination rate was defined by whether children received all recommended vaccines (4+ DTaP/DTP/DT; 3+ polio; 1+ measles-containing vaccine; full series Hib; 3+ Hep B; 1+ varicella at or after 12 months of age; and 4+ PCV). Eleven states were excluded from analysis due to fewer than 30 non-Hispanic Black respondents. We investigated the relationship between state-level structural racism scores for non-Hispanic Black individuals and calculated vaccination rate differences by linear regression analyses. Additionally, we examined the relationship in states that allowed religious exemptions for childhood vaccinations.

Results

At the state level, higher structural racism scores were associated with greater disparities in childhood vaccination rates between non-Hispanic Black and non-Hispanic White children (Figure 1). Importantly, these associations were significant only in states that allowed religious exemptions for childhood vaccinations (Figure 2, p = 0.046).

Conclusion

When childhood vaccination exemptions are permitted, state-level structural racism may significantly contribute to the observed racial disparities in vaccination rates among non-Hispanic Black children.

Disclosures

All Authors: No reported disclosures
509. Pseudomonas aeruginosa-specific CRISPR-Cas3 bacteriophage cocktail developed to treat respiratory and bloodstream infections
Authors: McMillan Lana , Penke Taylor , Tuson Hannah , McKee Robert , Baker Ethan , Trama Ashley
Published: January 2025

Background

New strategies are needed to combat infections due to multidrug-resistant (MDR) Pseudomonas aeruginosa. Bacteriophage therapy offers an effective, pathogen-specific, microbiome-sparing treatment with an orthogonal mechanism of action to that of small-molecule antibiotics. Here we describe the development and characterization of the P. aeruginosa-targeting 6-phage cocktail LBP-PA01.

Methods

High-throughput automated methods were used to isolate and characterize wild-type phages. Proprietary Locus-developed software was used to predict the most efficacious combinations of bacteriophages. Selected phages were engineered to express CRISPR-Cas3, and phages were combined into an optimal cocktail and subjected to in vitro antibacterial activity characterization including assessments of bacteriophage and cocktail host range by liquid growth curve assay and by plaque assay, bactericidal activity in the presence of mucin matrices using EpiAirwayTM human airway epithelium tissues, biofilm degradation and inhibition. In vivo efficacy was tested in immuno- compentent mouse models of lower respiratory tract infection with LBP-PA01 administered intranasally and intravenously as well as in a rat model of blood stream infection with intravenous administration.

Results

>2800 individual bacteriophage were discovered through high throughput methods. Cocktail prediction and optimization resulted in the final combination of 6 unique bacteriophage, LBP-PA01, which was tested against 570 diverse contemporary P. aeruginosa clinical isolates from patients with respiratory or bloodstream infections. The cocktail showed a host range of 97.3% and efficacy against biofilms and in the presence of mucin. In mouse models of acute lower respiratory tract infection and disseminating pulmonary infection and a rat model of bloodstream infection, LBP-PA01 produced multiple log reductions in CFU levels relative to vehicle treatment and superiority to standard-of-care antibiotics.

Conclusion

Based on the in vitro and mouse model data, LBP-PA01 is a strong candidate for advancement into the clinic for treatment for P. aeruginosa infections.

Disclosures

All Authors: No reported disclosures
512. Efficacy of Gepotidacin versus Nitrofurantoin in a Nitrofurantoin Not Susceptible Population: A Pooled Analysis of the EAGLE-2 and EAGLE-3 Randomized Controlled Trials in Uncomplicated Urinary Tract Infection
Authors: Dennison Jeremy , Sheets Amanda , Watts Sarah , Scangarella-Oman Nicole E , Butler Deborah , Breton John , Janmohamed Salim
Published: January 2025

Background

Two Phase 3 trials (EAGLE-2 [NCT04020341]/EAGLE-3 [NCT04187144]) showed that gepotidacin, a first-in-class triazaacenaphthylene antibacterial, was non-inferior to nitrofurantoin (NTF) in treating uncomplicated urinary tract infection (uUTI) caused by NTF-susceptible (NTF-S) qualifying uropathogens (≥ 105 CFU/mL).1 This study evaluates gepotidacin efficacy in the pooled EAGLE-2/3 microbiological intent-to-treat (micro-ITT) NTF not susceptible (NTF-NS) population.

Methods

In EAGLE-2/3, female patients aged ≥ 12 years with ≥ 2 uUTI symptoms received oral gepotidacin (1500mg) or NTF (100mg) twice-daily for 5 days.1 In this study, therapeutic, clinical and microbiological response (defined in tables) at test-of-cure (Day 10–13) were assessed in the pooled EAGLE-2/3 micro-ITT NTF-NS and NTF-S populations and across patient subgroups.

Results

Of the 1421 micro-ITT patients, 220 (15%) had NTF-NS uropathogens and 1201 (85%) had NTF-S uropathogens. The most common baseline uropathogens were Escherichia coli (90%) in the NTF-S population, and Klebsiella pneumoniae (31%), Proteus mirabilis (26%), and E. coli (24%) in the NTF-NS population (Table 1). Across key subgroups, the proportion of patients with NTF-NS uropathogens was broadly similar to the overall population (except Hispanic/Latinx, Black race and US subgroups which were numerically higher; Figure 1). For efficacy outcomes, treatment differences were higher in the NTF-NS vs the NTF-S population, and, as expected, favored gepotidacin vs NTF (Table 2). Treatment differences in therapeutic success were numerically higher across key subgroups in the NTF-NS vs the NTF-S population (Figure 2).

Conclusion

Gepotidacin was efficacious in both populations, and across subgroups, with a higher therapeutic treatment difference in the NTF-NS vs the NTF-S population. Gepotidacin could offer benefit in patients with uUTI, including those with NTF-NS uropathogens.

1. Wagenlehner F, et al. Lancet 2024;403:741–55.

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) Sarah Watts, MSc, GSK: Employee|GSK: Stocks/Bonds (Public Company) 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) Salim Janmohamed, MD, GSK: Employee|GSK: Stocks/Bonds (Public Company)
P-1472. Cefiderocol Remains Highly Active Against Carbapenemase-Producing Enterobacterales
Authors: DeJonge Boudewijn L , Nguyen Sean T , Bryowsky Jason J , Maher Joshua , Mendes Rodrigo , Longshaw Christopher M , Takemura Miki , Yamano Yoshinori
Published: January 2025

Background

Carbapenem-resistance in Enterobacterales is mediated by the acquisition of β-lactamases, including serine carbapenemases (KPC and OXA-48) and metallo-β-lactamases (NDM, IMP and VIM). Cefiderocol (CFDC) is a siderophore conjugated cephalosporin with good stability against all classes of β-lactamases. In this study, in vitro activity for CFDC and comparator agents was assessed against meropenem and/or imipenem non-susceptible carbapenemase-producing (CP) isolates that were collected between 2020-2022 in Europe and the USA as part of the SENTRY Antimicrobial Surveillance Program.Table 1.Susceptibility for cefiderocol and comparator agents against meropenem and/or imipenem non-susceptible carbapenemase-producing Enterobacterales isolates collected from European and US hospitals as part of the SENTRY surveillance program during 2020-2022.

Methods

A total of 24,084 Enterobacterales were collected and minimum inhibitory concentrations (MIC) for compactor agents were determined according to CLSI guidelines using broth microdilution with cation-adjusted Mueller-Hinton broth (CAMHB), while for CFDC iron-depleted CAMHB was used. Susceptibility was assessed according to 2024 CLSI, FDA, and EUCAST breakpoints. Isolates non-susceptible for meropenem and/or imipenem, based on CLSI breakpoints (n=2,029), were subjected to whole genome sequencing to determine their carbapenemase content.

Results

474 isolates (23.4%) produced carbapenemases, most of them being KPC enzymes (54.2%), followed by OXA-48-like (24.5%), NDM (20.3%), and VIM (6.5%). Three isolates (0.6%, all S. marcescens) produced SEM enzymes and one K. pneumoniae (0.2%) produced an IMP. CFDC was highly active against CP isolates, with >90% of the KPC-, OXA-48-like, VIM-, IMP-, and SEM-producing and 85.4% of NDM-producing isolates being susceptible according to FDA/CLSI breakpoints (Table 1). While susceptibilities were lower when applying EUCAST breakpoints, because of the number of isolates with CFDC MIC values of 4 µg/mL, CFDC remained one of the most active agents. Compared to β-lactam-β-lactamase inhibitor combinations, CFDC showed higher susceptibility against the CP isolates, mainly the result of the increased stability of CFDC against metallo-β-lactamases.

Conclusion

CFDC is active against CP Enterobacterales, regardless of the carbapenemase produced. In contrast, β-lactam-β-lactamase inhibitor combinations showed variable activity. CFDC should be considered as a treatment option when CP Enterobacterales are encountered.

Disclosures

Boudewijn L. DeJonge, PhD, Shionogi Inc.: Employee Sean T. Nguyen, PharmD, Shionogi Inc.: Employee Jason J. Bryowsky, PharmD, MS, Shionogi: Employee Rodrigo Mendes, PhD, Shionogi & Co., Ltd.: Grant/Research Support Christopher M. Longshaw, PhD, Shionogi BV: Employee Miki Takemura, n/a, Shionogi & Co., Ltd.: Employee Yoshinori Yamano, PhD, Shionogi & Co., Ltd.: Employee
516. Cytomegalovirus (CMV) Saliva Shedding Kinetics in Children with Congenital Cytomegalovirus Infection (cCMV)
Authors: Pinninti Swetha , Pati Sunil , Novak Zdenek , Fowler Karen , Boppana Suresh , Ross Shannon
Published: January 2025

Background

CMV is the most common cause of congenital viral infection worldwide and the leading cause of non-genetic sensorineural hearing loss (SNHL). Children with congenital CMV infection (cCMV) shed the virus in urine and saliva for prolonged but variable durations. However, data on CMV saliva shedding kinetics in cCMV is limited because of the lack of longitudinal virological follow-up. The objective of this study is to describe CMV shedding kinetics in saliva during early childhood in a cohort of children with cCMV identified through universal newborn screening.

Methods

As part of the CMV and Hearing Multicenter Screening study (CHIMES), >100,000 newborns were screened for cCMV. Data from 211 children with ≥ 5 visits each with audiological follow-up and serial saliva samples collected every six months through four years of life was analyzed. Saliva CMV shedding duration and intermittent shedding according to presence of newborn symptoms, hearing status and antiviral treatment are described.

Results

Of the 211 children with cCMV, 14 received anti-viral treatment in early infancy. Most children shed CMV in saliva during infancy with a gradual decrease in frequency on follow-up (Figure 1). The median duration of shedding did not differ between children with asymptomatic and symptomatic cCMV (25 vs 26 months respectively; p = 0.61); children with SNHL and normal hearing (22 vs 26 months respectively; p = 0.26); and between those treated with antiviral agents and untreated children (23 vs 25 months; p = 0.9). Salivary CMV shedding was intermittent in about a third of the cohort (71/197 - 36%), mostly (91.5%) in those with asymptomatic cCMV. CMV shedding duration was significantly longer in children with intermittent shedding compared to those who did not (34 vs 17 months; p < 0.0001).

Conclusion

In this large cohort of children with cCMV identified through newborn screening, children shed CMV DNA in saliva for a median of two years, irrespective of newborn symptoms, hearing status, and receipt of anti-viral therapy. A third of the cohort shed CMV intermittently. Based on these observations, we conclude that a negative saliva CMV PCR result during infancy in newborns with findings consistent with cCMV but not tested in the newborn period likely excludes a diagnosis of cCMV.

Disclosures

Swetha Pinninti, MD, Moderna: Grant/Research Support|Pfizer: Grant/Research Support Karen Fowler, DrPH, Moderna: Advisor/Consultant Suresh Boppana, MD, GSK: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Grant/Research Support
P-1513. In Vitro Activity of Ceftaroline against Bacterial Pathogens from Pediatric Patients Collected During the ATLAS Global Surveillance Program in 2018-2022
Authors: Hackel Meredith , Stone Gregory , Sahm Daniel F
Published: January 2025

Background

The parenteral cephem ceftaroline fosamil is approved for treatment of adults and children with complicated skin and soft tissue infections (SSTI) and community-acquired bacterial pneumonia (CABP) caused by susceptible isolates of Staphylococcus aureus (methicillin-resistant [MRSA; SSTI] and methicillin-susceptible [MSSA; SSTI and CABP]), β-hemolytic streptococci (Streptococcus pyogenes and Streptococcus agalactiae [SSTI]); Streptococcus pneumoniae (CABP, including concurrent bacteremia), Haemophilus influenzae (CABP), and isolates of Escherichia coli, Klebsiella pneumoniae and Klebsiella oxytoca (SSTI and CABP). Several pathogens causing CABP are also frequently associated with bloodstream infections (BSI). This study examined the in vitro susceptibility to ceftaroline and comparator agents among pathogens isolated from pediatric patients with SSTI, respiratory tract infections (RTI), and BSI as part of the Antimicrobial Testing Leadership and Surveillance (ATLAS) surveillance program in 2018-2022.

Methods

16,533 non-duplicate, clinically relevant isolates of S. aureus, β-hemolytic streptococci, S. pneumoniae, H. influenzae, M. catarrhalis and Enterobacterales were collected from patients aged 0-17 years old with BSI, RTI and SSTI by 285 medical centres in 60 countries. In vitro susceptibility to ceftaroline was determined by CLSI broth microdilution and results were interpreted using CLSI 2024 breakpoints where available. Extended spectrum β-lactamase (ESBL) screening was performed using the CLSI M100 method.

Results

The in vitro activity of ceftaroline is summarized in the table. 100% of MSSA and β-hemolytic streptococci isolates, >99% of S. pneumoniae, >99% of H. influenzae, and >92% of ESBL screen-negative E. coli, K. pneumoniae, K. oxytoca and P. mirabilis collected from all pediatric patients combined tested as susceptible to ceftaroline, as did >97% of MRSA. M. catarrhalis ceftaroline MIC values ranged from ≤0.06 - 8 µg/mL, with an MIC90 of 0.25 mg/L. Susceptibility was consistant across each of the age groups.

Conclusion

Ceftaroline demonstrated potent in vitro activity against a global collection of clinically relevant pathogens collected from pediatric patients.

Disclosures

Daniel F. Sahm, PhD, Pfizer, Inc.: Advisor/Consultant