bluuebunny/crossref_metadata_2025 huggingface dataset:
1844. HIV Home Care - The First Five Years
Authors: Khaja Sumaiya F , Keri Vishakh C , McClendon Tammie , Veltman Jennifer , Newman Gretchen Snoeyenbos
Published: November 2023

Background

To achieve HIV care continuum goals, novel modes of HIV care are needed. In 2017, the Wayne State University Home Care Program (HCP) was launched in Detroit, Michigan. The primary purpose of this program is to re-engage people with HIV (PWH) who have been unable to attend regular clinic visits through an intensive, in-home model of HIV care. This study evaluates the outcomes of the first 5 years of this program.

Methods

We conducted a retrospective cohort analysis of the 81 patients enrolled in the HCP from inception in 2017 to December, 2022. We evaluated duration of participation, reason for discharge from the program, and effect of a full year of program participation on viral suppression (viral load ≤ 20 copies/mL) and CD4 count (above or below 200 cells/mm3). Patients who did not have at least 1 year of participation were excluded from analysis of change in VL and CD4 count. McNemar test of significance was used, p value of < 0.05 was considered significant.

Results

Most of the patients enrolled in the HCP were African American (95.1%) and male (65.4%). Common primary barriers to clinic visits were transportation (27.2%) and stigma (25.9%). The median duration spent in the HCP was 924 days (approximately 2.5 years). At entry, 15.3% of patients had a suppressed viral load, and after the first year of enrollment, 52.5% of patients achieved viral load suppression (p< 0.001). Similarly, 72.9% of patients achieved a CD4 ≥ 200 cells/mm3 after a year when compared to 57.6% of patients at entry with CD4 ≥ 200 cells/mm3 (p=0.012). Of the 81 patients enrolled during the study period, 28 patients (50%) returned to clinic-based care, out of which 21 patients (91.3%) were retained in care and 2 (8.7%) were lost to follow-up. Total of 11 patients (19.6%) died during the study period.Table 2:Home Care Program Outcomes

Conclusion

The Wayne State University Home Care Program is an innovative model to re-engage and maintain PWH who are unable to receive care in traditional settings. By removing physical and stigma-related barriers, the HCP was able to improve viral load suppression and CD4 count among an ill and “hard to reach” cohort. Additionally, the HCP empowered patients to successfully return to clinic-based care.

Disclosures

All Authors: No reported disclosures
1849. Impact of Medicaid Expansion on Human Immunodeficiency Virus Outcomes in Nebraska
Authors: McCluskey James M , Furl Renae , Arroyo Monica , Fadul Nada
Published: November 2023

Background

Human immunodeficiency virus (HIV) viral suppression (VS) is a major predictor for improved clinical outcomes and decreased viral transmission in patients with HIV (PWH). There is evidence to suggest that enrollment in the Affordable Care Act (ACA) qualified health plan is associated with improved VS, however there is inconsistency in the literature on whether Medicaid enrollment can lead to similar outcomes. Previous research has shown that PWH living in Medicaid expansion states are more likely to be covered by Medicaid and less likely to be uninsured compared to those who live in non-expansion states. In 2014, the ACA Medicaid expansion went into effect and expanded Medicaid coverage to most adults with an income up to 138% of the Federal Poverty Level (PFL), which is $14,580 for an individual in 2023. Nebraska implemented the expansion October 2020. This provided an opportunity to further evaluate this gap in the literature using the data from the main provider of HIV care in Nebraska, the University of Nebraska Medical Center Specialty Care Center (UNMC SCC).

Methods

PWH were recruited from UNMC SCC for a retrospective observational study that included all patients 19 years of age or older that had at least one HIV provider clinic visit in the preceding 12 months before October 2020. If the patients had unknown income or were below 138% FPL and were not already enrolled in Medicare or out of state Medicaid, they were considered eligible for Medicaid expansion. PWH that were eligible and those that were not eligible for Medicaid expansion then had follow up viral loads compared to assess for VS.

Results

A diverse group of 1,069 patients were included in the study (Table 1). No statistically significant result was found between baseline VS, however those that were not eligible for Medicaid expansion showed a greater level of VS at follow up (Table 2), p=0.003.

Conclusion

This retrospective study found that approximately 1 year after Medicaid expansion in Nebraska, PWH that were not eligible for Medicaid expansion had better VS. This could be explained by a lack of those that were newly eligible for Medicaid being able to enroll among other reasons. This finding warrants further evaluation to assess for barriers to care, including but not limited to, Medicaid enrollment and its contribution to HIV VS.

Disclosures

All Authors: No reported disclosures
1850. Association between social vulnerability and Streptococcus pneumoniae antimicrobial resistance in US adults
Authors: Mohanty Salini , Ye Gang , Sheets Charles , Cossrow Nicole , Yu Kalvin , White Meghan , Klinker Kenneth P , Gupta Vikas
Published: November 2023

Background

Antibiotic resistant infections affect more than 2.8 million people in the US each year and disproportionately impact those who are socially vulnerable. The objective of this study was to evaluate the association between Streptococcus pneumoniae (SP) antimicrobial resistance (AMR) and the CDC/ATSDR Social Vulnerability Index (SVI) in the US.

Methods

Adult patients (≥ 18 years) with 30-day nonduplicate SP isolates from ambulatory/hospital settings from January 2011–December 2022 who had zip codes of residence reported were evaluated across 177 facilities in the BD Insights Research Database (Becton, Dickinson & Co., Franklin Lakes, NJ). Isolates were identified as SP AMR if they were intermediate or resistant to ≥ 1 macrolide, tetracycline, extended-spectrum cephalosporin, or penicillin. Isolates from adult patients with zip code of residence reported were matched with county-level CDC SVI data, and associations between SVI score (overall and by each theme) and SP AMR were evaluated using generalized estimating equations with repeated measurements within county to account for within-cluster correlations (Figure 1, Table 1).

Results

Of the 8,008 unique SP isolates linked to 574 US counties, the overall rate of SP AMR was 49.9%. A significant association between the socioeconomic status (SES) theme and SP AMR was detected with higher SVI scores (indicating greater social vulnerability) associated with greater risk of AMR. On average, a single decile increase in SES theme ranking score was observed to be associated with a 1.28% increased risk of AMR (95% confidence interval [CI], 0.61%, 1.95%; P=0.0002; Table 1). Similarly, a single decile increase in household characteristic theme ranking score was observed to be associated with a 0.81% increased risk in SP AMR (95% CI,0.13%, 1.49%; P=0.0197). However, no association between the racial and ethnic minority status theme, the housing type and transportation theme, and overall SVI score and SP AMR were observed.

Conclusion

Higher SES and household characteristic ranking scores (indicating greater social vulnerability) were observed to be associated with higher risk of SP AMR. These results contribute to evidence linking AMR to health disparities and inequities and suggest that AMR is impacted by social determinants of health.

Disclosures

Salini Mohanty, DrPH, MPH, Employee of Merck & Co., Inc.: Stocks/Bonds Gang Ye, PhD, Becton Dickinson and Company: employee Charles Sheets, MS, Becton Dickinson: Data Analysis Nicole Cossrow, PhD, Merck: Stocks/Bonds Kalvin Yu, MD, FIDSA, BD: Stocks/Bonds Meghan White, PharmD, Merck: Employee|Merck: Stocks/Bonds Kenneth P. Klinker, PharmD, Merck & Co., Inc: Employee|Merck & Co., Inc: Stocks/Bonds Vikas Gupta, PharmD, Becton, Dickinson and Company (BD): Employee of BD|Becton, Dickinson and Company (BD): Stocks/Bonds
1852. Harnessing the Power of Artificial Intelligence to Mitigate the HIV/STI Epidemic: Identifying Free Resources for Prevention and Treatment
Authors: Patel Premalkumar M , Prieto Freddie , Singh Yavani , Tuda Claudio , Rivera Cynthia
Published: November 2023

Background

According to the CDC, 1.2 million people in the US have contracted HIV, with 13% of them being unaware of their diagnosis and treatment options. Only 25% of the eligible population is using PrEP. At any given time, 1 in 5 people in the US have STIs, but many do not seek medical attention due to the associated stigma and discrimination. Advanced technologies, such as AI, are being utilized to enhance healthcare delivery and address disparities in accessing health services. AI algorithms can help reduce the spread of HIV and STIs and prevent long-term complications.

HIV/STI free clinic information for providers/patients

HIV/STI free resources information generated by ChatGPT

HIV/STI free clinic information near Miami generated by ChatGPT

Methods

To access ChatBot in ChatGPT for finding resources, we followed these steps:

Results

The Chatbot was utilized by the ChatGPT application and conducted an extensive search for HIV/STI testing and treatment resources in the US. The search involved identifying potential resources from numerous sources, such as Planned Parenthood clinics, community health centers, care resources, AHF and the National HIV and STD Testing Resources websites. The search was focused on determining whether insurance was required, the type of services provided, and contact information for the potential resources. Screenshots attached as images.

Conclusion

In conclusion, the utilization of artificial intelligence in finding free resources for HIV/STI prevention and treatment can be a game-changer in addressing the HIV epidemic. With its ability to identify available resources and high-risk populations, AI can greatly aid in allocating resources more efficiently towards reducing barriers that impede access to HIV/STI prevention and treatment.Further research is needed to explore how best AI can enhance these findings but undoubtedly it could be valuable if applied correctly. Overall, the implementation of AI-based solutions may hold significant promise for addressing public health challenges posed by STIs/HIV infections on a global scale.

Disclosures

All Authors: No reported disclosures
1862. Understanding Care Experiences Amongst Immigrant and Refugee Clients in a Ryan-White Funded HIV Clinic: Insights to Improve Culturally Competent Care
Authors: Zhang Sirey , Altomare Antonia , Zuckerman Richard A
Published: November 2023

Background

Immigrants and refugees receiving HIV care may have challenges accessing effective care due to their unique social determinants of health. In this pilot project, we gathered client and caregiver experiences to improve care systems for our immigrant and refugee clients.

Methods

Participant observation and standardized ethnographic interviews were conducted with 18 clients and 4 caregivers in the HIV clinics at Dartmouth Health. Community support was determined by asking clients if there are family or other members of their immigrant community involved in supporting their care. Clients received gift cards for their time. The study was funded through the IDSA G.E.R.M. grant.

Results

Clients encompassed the spectrum of documentation status and length of residence. Overall, clients seemed satisfied with their care; however, in addition to concerns of how their diagnoses impact documentation and employment status, clients cited fears about the impact on their community standing, with some clients refusing interpreters for fears of being identified. Seven of the 18 total clients reported poor community support. This group included the 2 clients who required more follow-up visits (9 and 4 visits per year) and the only client with an unsuppressed viral load. Congruently, caregivers perceived better adherence and participation when they were able to incorporate family and community support into the client’s care. Clients also expressed that it was important for them to incorporate their sense of self and community within the context of the predominant American culture.

Conclusion

We found that for most of our clients, “culturally competent care” is a spectrum of integration of their indigenous and new cultural experiences. Care outcomes are improved when the clinic supports a client’s need to maintain community support, legal standing, and employment, all of which are key factors in immigrant/refugee success in a new country. However, fear of disclosure can be a barrier to establishing this support, requiring the clinic team to take an active role in building care support while ensuring privacy. Moving forward, we plan to restructure culturally competent care in our clinics in ways that include these important components.

Disclosures

All Authors: No reported disclosures
1864. Recruitment of Participants for Qualitative Research in Marginalized Populations
Authors: Adusumelli Yamini , Tabatneck Mary , Sherman Susan N , Lamb Gabriella S , Sabharwal Vishakha , Goldmann Don , Epee-Bounya Alexandra , Haberer Jessica , Sandora Thomas J , Campbell Jeffrey I
Published: November 2023

Background

There is limited understanding of barriers to participation in pediatric qualitative research, particularly for studies seeking to understand diseases primarily affecting marginalized and hard-to-reach populations.

Methods

We conducted a retrospective cohort study of participants and non-participants invited to enroll in a qualitative study of pediatric tuberculosis (TB) infection care. Potential participants in the initial study were adult caregivers of children diagnosed with TB infection between 2016-2021 in Boston. Most children were immigrants or children of immigrants, and all caregivers were English- or Spanish-speaking. We sent letters in English and Spanish to patients’ primary caregivers, and followed up with up to 2 phone calls. Enrolled participants completed a virtual qualitative interview. We compared characteristics of individuals who participated vs did not participate, and summarized reasons for non-participation.

Results

Of 61 invited caregivers, 19 (31%) enrolled in the initial qualitative study. Table 1 compares characteristics of participants and non-participants. The primary reason for non-participation was inability to contact caregivers (n=27, 64%). A total of 11 (26%) caregivers declined participation, and 4 (10%) participants were unable to join or complete interviews after initially agreeing to participate. Non-completion of TB infection care was significantly associated with non-participation in the qualitative study (P=0.049). We did not observe significant differences by language, insurance, relationship of caregiver to patient, or time from diagnosis to study invitation between participants and non-participants.

Conclusion

Inability to contact potential participants, participants’ lack of time, and lack of shared illness understanding posed barriers to recruitment in this qualitative study. Our findings suggest that alternative contact strategies (e.g. email, text messages), use of short interviews, and strategies to rapidly communicate illness scripts should be studied to improve inclusion in similar studies. While we were able to enroll participants who had not completed TB infection care, additional methods are needed to obtain qualitative perspectives from individuals who disengage from care.

Disclosures

Jessica Haberer, MD, MS, Merck: Advisor/Consultant
1866. Can β-lactam Combinations Restore Susceptibility Against Mycobacterium avium Complex: Exploring a New Approach to a “Difficult to Treat” Opportunistic Pathogen
Authors: Al-Jabri Maha Y , Dousa Khalid M , Wilson Brigid , Holland Steven M , Bonomo Robert A
Published: November 2023

Background

Mycobacterium avium Complex (MAC) are nontuberculous mycobacteria (NTM) responsible for chronic and debilitating diseases, with rising global prevalence. Clinical relapse/reinfection rates of MAC following treatment with first-line therapies range from 25% to 45%. β-lactam antibiotics are not utilized for the treatment of MAC due to clinically high minimum inhibitory concentrations (MICs). Recent studies have explored the effect of combining β-lactam antibiotics to reduce the MICs of other NTMs by inactivating multiple targets in the peptidoglycan synthesis pathway. Our hypothesis is that the cell wall of MAC is similar to that of other NTMs and thus, interrupting the peptidoglycan synthesis pathway using β-lactam combinations would result in lower MICs. In this study, we aim to determine the MICs of meropenem (MEM) in combination with ceftaroline (CPT), cefdinir (CDR), and cefuroxime (CXM) against MAC.

Methods

A total of 31 clinical MAC isolates underwent susceptibility testing using broth microdilution method. MICs were tested for MEM, CPT, CDR, and CXM, alone, as well as combination of MEM plus either CPT, CDR, or CXM.

Results

The susceptibility of MAC isolates to MEM was significantly enhanced when combined with CPT, CDR, and CXM. This effect was most prominent with the addition of CPT, with MIC50/MIC90 of < 0.125/1 µg/mL (compared to 16/64 µg/mL for MEM alone and 16/128 µg/mL for CPT alone), and CDR, with MIC50/MIC90 of < 0.125/2 µg/mL (compared to 16/ >128 µg/mL for CDR alone) (Table 1). The distribution of MICs of β-lactams alone and in combination demonstrates a “left shift” towards lower MIC values for the latter. A Wilcoxon signed-rank analysis confirmed that the change in MIC values for all β-lactam combinations compared to β-lactams alone reached statistical significance (p-value < 0.001, Figure 2).

Conclusion

In this study, we demonstrate that the susceptibility of MAC to MEM is restored with the addition of CPT and CDR. Our data support further exploration of β-lactam combinations as a therapeutic strategy against resistant MAC infections, refractory cases, and when first-line agents are poorly tolerated. Furthermore, our observations suggest that MAC and other NTMs share cell-wall synthetic pathways and that β-lactam combinations can overcome resistance.

Disclosures

Robert A. bonomo, MD, Entasis, Merck, VenatoRx, Wockhardt: Grant/Research Support
1869. Knowledge about and Perceptions of Latent Tuberculosis Infection (LTBI) among Physicians and Advanced Practice Providers at Tufts Medical Center
Authors: Boomsma Cassidy , Vindenes Tine
Published: November 2023

Background

Mycobacterium Tuberculosis (TB) is a leading cause of infectious disease mortality worldwide. Most active TB cases result from reactivation of latent tuberculosis infection (LTBI). A large reservoir of latent TB is a major public health problem worldwide and in the United States. A better understanding of provider perspectives on LTBI could improve a sub-optimal LTBI care cascade.

Methods

A 13-question survey was fielded to attending physicians, fellows, and advanced practice providers working in the infectious disease, pulmonary/critical care, and general medicine departments at Tufts Medical Center (TMC), an academic tertiary care center in Boston, Massachusetts.

Results

The response rate of the survey was 33% (62/186). Only 17 (30.9%) providers were able to correctly identify all indications for screening. When asked how they decide who to treat, 26.8% (15/56) of providers selected that they would refer their patient to another specialist. Overall, provider confidence in LTBI management decreased along the care cascade (Figure 1). Infectious disease providers expressed more confidence in management than general medicine and pulmonary/critical care providers. The two most observed issues/barriers to care for patients were language, reported by 39 (76.5%) providers, and lack of knowledge or understanding about TB, reported by 39 (76.5%) providers. The two most selected interventions to improve LTBI care at TMC were use of in-person language interpreters, chosen by 37 (71.2%) providers, and information pamphlets available in patients’ preferred languages, chosen by 36 (69.2%) providers.

Providers were asked “On a scale of 1-5, (“1” = not at all, and “5” = perfectly) “How confident are you in your ability to do the following” for the listed management tasks.

Conclusion

Results suggest that providers believe the largest barriers to patient LTBI treatment completion are due to a lack of patient comprehension about their infection. Improving patient understanding could be accomplished through in-person interpreters, information pamphlets about LTBI in patients’ preferred languages, and forming community partnerships to improve awareness and understanding of the risks of LTBI. Additionally, ensuring that providers feel confident in their ability to manage LTBI, are updated on screening guidelines, and have referral resources when needed, could help close the gaps in the LTBI care cascade.

Disclosures

All Authors: No reported disclosures
1882. Contact Investigation of Congenital Tuberculosis in a Neonatal Intensive Care Unit in South Korea
Authors: Lee Sojeong , Namgung Songhee , Jo Eunbyeol , Yun Mina , Kim Ja Young , Lee Yumi , Jeong Jihye , Kim Sun Kyung , Park So-Yeon , Lim Young-Ju , Kim Eun Ok , Jung Jiwon , Lee Jina , Lee Byong Sop , Kim Sung-Han
Published: November 2023

Background

Congenital tuberculosis (TB) is uncommon and difficult to detect in neonates due to its nonspecific symptoms. We conducted a contact investigation of infants and healthcare workers (HCWs) exposed to a neonate with congenital TB in a neonatal ICU (NICU) in Korea.

Methods

A premature infant born was admitted to NICU on September 16, 2022. On October 24, the infant's mother was diagnosed with miliary TB, and infant’s sputum AFB stain showed 4 positive results. All NICU infants and HCWs during the same period were screened for active pulmonary TB using chest radiography (CXR) immediately. Exposed infants were evaluated with a TST and CXR three months after exposure. Interferon-Gamma Release Assay (IGRA) testing was performed on those with a positive TST or abnormal CXR finding. Prophylactic rifampin was provided to the exposed infants for 3 months, as index had isoniazid-resistant M. tuberculosis infection. Exposed HCWs underwent IGRA testing immediately after exposure (1st IGRA) and at 8 to 10 weeks post-exposure (2nd IGRA), and CXR was performed 6 months after exposure.

Results

Five out of 82 exposed infants had positive TST (≥ 10 mm) results, while all 31 infants who underwent IGRA testing had negative results. All five with positive TST had received BCG vaccination a median 105 days before. Of the 119 exposed HCWs, three had a conversion; two had negative results (on annual IGRA testing performed according to the national TB prevention Act) before exposure and positive at 1st IGRA test, and one had negative 1st IGRA test then positive 2nd IGRA test. None had active TB during 6-month follow-up.

Conclusion

We found that 6% of exposed infants had positive TST results and 0% had positive IGRA, while 2.5% of exposed HCWs had conversion. Considering the possibility of false positive TST results due to prior BCG vaccination, the chance of transmission to the infants would be 0%; otherwise, it would be 6.1%.

Disclosures

All Authors: No reported disclosures
1888. The Impact of COVID-19 on Adherence to Directly Observed Therapy Among a Tuberculosis Treatment Cohort
Authors: Overbeck Victoria , Malatesta Samantha , Carney Tara , Myers Bronwyn , Parry Charles , Horsburgh C Robert , Theron Daniel , White Laura F , Warren Robin , Jacobson Karen R , Bouton Tara C
Published: November 2023

Background

The COVID-19 pandemic negatively impacted all levels of tuberculosis (TB) treatment services, including directly observed therapy (DOT) programs used to promote medication adherence. We compared the rate of adherence to DOT before and during the pandemic among observational research study participants on drug-susceptible (DS)-TB therapy in Worcester, South Africa.

Methods

We analyzed adherence data from 263 study participants who participated in DOT for the duration of their DS-TB treatment. Participants enrolled between May 16, 2017, to September 27, 2019, and October 16, 2020, to March 4, 2022, were classified as pre- and post-COVID lockdown groups respectively. Adherence to DOT was used as a proxy for treatment adherence and defined as the number of successful DOT encounter days. Negative binomial regression models were used to compare the rate of non-adherence to DOT between the two groups. A sensitivity analysis was conducted that excluded participants in the post-COVID lockdown group enrolled after May 30, 2021, when South Africa increased their COVID-19 related restrictions in response to a third COVID wave (Figure 1).

Results

The overall median rate of DOT adherence across both groups was 87.1% (IQR: 75.47%, 92.64%). The adjusted rate of non-adherence to DOT was higher in the post-COVID lockdown group (aIRR = 1.42, 95% CI = 1.04 – 1.96, p = 0.028) compared to the pre-COVID lockdown group, after adjusting for age, sex, employment status, household hunger, depression risk, and smoked illicit drug use. The rate of non-adherence to DOT was even greater in the post-COVID group (aIRR = 1.74, 95% CI = 1.17–2.67; p=0.006) when participants enrolled after May 30, 2021, were excluded from the analysis (Figure 2).

Solid lines are weighted least squares regression line with local fitting and 95% confidence intervals, implemented with R function geom_smooth.

Solid lines are weighted least squares regression line with local fitting and 95% confidence intervals, implemented with R function geom_smooth. Rectangle represents period that study enrollment was paused due to COVID-19 restrictions (March 26, 2020 – September 20, 2020).

Conclusion

The COVID-19 pandemic had significant adverse effects on participants’ adherence to a TB DOT programs in this setting. The change in DOT adherence persisted even after adjusting for measurable socioeconomic and behavioral variables and was most notable immediately following the first wave of COVID-19 infections. Further work is needed to understand barriers to treatment adherence that were exacerbated by the COVID-19 pandemic itself and lockdowns in order to identify individuals needing additional supports and ways to improve systems even during non-pandemic times.

Disclosures

All Authors: No reported disclosures
2938. Hepatitis C Virus Care Continuum in the Direct-acting Antiviral Era within the US Veterans Health Administration
Authors: Varley Cara D , Lowy Elliott , Cartwright Emily J , Morgan Timothy R , Rozenberg-Ben-Dror Karine , Beste Lauren , Maier Marissa
Published: November 2023

Background

Estimated hepatitis C prevalence within the Veterans Health Administration is higher than the general population and is a risk factor for advanced liver disease and its associated complications. We describe the hepatitis C care continuum within the Veterans Health Administration between January 1, 2014 and December 31, 2022.

Methods

Individuals in Veterans Health Administration care 2021-2022 who were eligible for direct-acting antiviral treatment between January 1, 2014 and December 31, 2022 comprised our cohort. We evaluated the proportion of Veterans who progressed through each step of the hepatitis C care continuum, and identified factors associated with initiating direct-acting antivirals, achieving sustained virologic response, and repeat hepatitis C viremia after achieving sustained virologic response.

Results

We identified 133,732 Veterans with hepatitis C viremia during our study timeframe. Hepatitis C treatment was initiated in 107,134 (80.1%), with sustained virologic response achieved in 98,136 (91.6%). In those who achieved sustained virologic response, 1,097 (1.1%) had subsequent repeat viremia and 579 (52.8%) were retreated for hepatitis C. Veterans of younger ages were less likely to initiate treatment and achieve sustained virologic response, and more likely to have repeat viremia. Stimulant use and unstable housing were negatively associated with each step of the hepatitis C care continuum.Table 1:Characteristics of Veterans with HCV ViremiaTable 2:Factors Associated with DAA Treatment Initiation in those with HCV ViremiaFigure 1:Overview of the VHA Hepatitis C Care Continuum as of December 31, 2022

Conclusion

The Veterans Health Administration has treated 80% of Veterans with hepatitis C with direct-acting antiviral therapy since its approval in 2014 and achieved sustained virologic response in more than 90% of those treated. Repeat viremia is rare and is associated with younger age, unstable housing, opioid use, and stimulant use. Ongoing efforts are needed to reach younger Veterans, and Veterans with unstable housing or substance use disorders.

Disclosures

All Authors: No reported disclosures
2154. Cross-resistance of Ceftolozane-Tazobactam and Imipenem-Relebactam Against Clinical P. aeruginosa Isolates from Bloodstream and Respiratory Tract Infections– SMART United States 2019-2021
Authors: Lob Sibylle , Wise Mark G , Bauer Karri , Siddiqui Fakhar , Hilbert David W , Esterly John , DeRyke C Andrew , Young Katherine , Motyl Mary , Sahm Daniel F
Published: November 2023

Background

Antimicrobial resistance among Pseudomonas aeruginosa is challenging with limited treatment options. Ceftolozane/tazobactam (C/T) maintains activity against P. aeruginosa resistant to commonly used β-lactams. Imipenem/relebactam (IMI/REL) can restore the activity of IMI against P. aeruginosa. C/T and IMI/REL can be affected by different mechanisms of resistance, and pathogens can be nonsusceptible to one agent but susceptible to the other. We evaluated the activity of C/T and IMI/REL against P. aeruginosa isolates collected from patients with lower respiratory tract (LRTI) and bloodstream (BSI) infections in the United States as part of the global SMART surveillance program.

Methods

In 2019-2021, 24 US clinical labs collected up to 100 consecutive, aerobic or facultative, gram-negative pathogens from LRTI and up to 50 from BSI. Of 8643 collected isolates, 1986 (23%) were P. aeruginosa. Susceptibility was determined with CLSI broth microdilution and 2023 CLSI breakpoints.

Results

Among P. aeruginosa BSI and LRTI isolates, 88% were susceptible (S) to both C/T and IMI/REL, 2% were nonsusceptible (NS) to both agents; 8% were S to C/T but not to IMI/REL, and 2% were S to IMI/REL but not to C/T (Table 1). Among MDR and DTR isolates, 45% and 29%, respectively, were S to both C/T and IMI/REL and 11% and 20%, respectively, were NS to both. Among C/T-NS isolates, 57.3% and 44.0% were S to IMI/REL and ceftazidime/avibactam (CZA), respectively (Table 2). Among IMI/REL-NS isolates, 83% were C/T-S, 69% CZA-S, and < 43% were S to all other studied β-lactams and LVX. Among CZA-R isolates, 61% and 47% remained S to C/T and IMI/REL, respectively.

Conclusion

Resistance to both C/T and IMI/REL was not common among recent clinical isolates of P. aeruginosa from the US, and both agents represent important treatment options. A significant proportion of isolates NS to one agent were S to the other, especially among MDR and DTR isolates. The data suggest that susceptibility to both agents should be tested.

Disclosures

Sibylle Lob, MD, Merck & Co., Inc.: Honoraria Mark G Wise, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation Fakhar Siddiqui, MD, MBA, Merck & Co Inc.: Employee Daniel F. Sahm, PhD, Merck & Co., Inc.: Honoraria|Pfizer Inc.: Honoraria|Venatorx: Paid fees for conducting the study and abstract preparation
2161. Biofilm and Aggregate Formation as an Efficient Strategy Used by C. parapsilosis to Persist Echinocandin Treatment and Evade the Innate Immune Cells
Authors: Daneshnia Farnaz , Floyd Daniel , Hilmioğlu-Polat Süleyha , Ilkit Macit , Carvalho Agostinho , Munro Carol , Perlin David , Gabaldon Toni , Nobile Clarissa , Arastehfar Amir , Mansour Michael
Published: November 2023

Background

Biofilm and aggregate formation are thought to be critical strategies employed by fungal pathogens, such as Candida auris and Candida parapsilosis, to effectively colonize biotic and abiotic surfaces as well as to cause clonal outbreaks. Herein, we identified an immunocompetent patient experiencing persistent candidemia due to C. parapsilosis while under micafungin treatment. Four C. parapsilosis isolates were collected during the course of treatment, the initial isolate from the central venous catheter and the latter isolates from blood samples. We aimed to investigate microbiological attributes leading to immune evasion and micafungin therapeutic failure.

Methods

Whole genome sequencing (WGS) was employed to assess the genetic relatedness of the isolates. Detailed biofilm and aggregate formations were evaluated using confocal microscopy and cell wall staining and scanning electron microscopy was employed to assess cell wall changes. Interaction with primary neutrophils and macrophages and fungal burden in various organs of mice systemically infected with our isolates was carried out to assess the fitness.

Results

Whole-genome sequencing found isolates clonal. Interestingly, the latter isolates formed larger aggregates and thicker biofilm and a high concentration of micafungin was less effective against their biofilm structures. Detailed cell wall analysis found a concomitant incremental increase in mannan and a lower β-glucan and chitin of the latter isolates. Additionally, the latter isolates were less effectively phagocytosed by primary human macrophages and neutrophils, and macrophages infected with the latter isolates secreted significantly lesser proinflammatory cytokines, including TNFα and IL1β. Finally, mice infected with the latter isolates had a significantly higher burden in the kidney, liver, and spleen when compared to the initial isolate. Genomic changes underlying such morphological changes are under investigation, which will be used for transformation and functional studies.

Conclusion

Altogether, our study highlights that under certain conditions biofilm and aggregate formations can be employed by C. parapsilosis to effectively persist echinocandin treatment and evade the immune system.

Disclosures

Michael Mansour, MD, PhD, Thermofisher: Grant/Research Support
2181. Avibactam Prevents the in vitro Development of Imipenem Resistance in non-Carbapenemase-Producing Klebsiella pneumoniae
Authors: Quesille-Villalobos Ana M , Bolivar Consuelo , Nicolai Juan José , Herrera Veronica , Martinez Jose R W , Quiroz Valeria , Dias Lorena , Alcalde-Rico Manuel , Rafael Araos , Garcia Patricia , Munita José M
Published: November 2023

Background

Carbapenem resistance (CR) in Klebsiella pneumoniae is most frequently mediated by the production of carbapenemases. However, non-carbapenemase-producing K. pneumoniae (non-CP-Kpn) have been well documented. Overexpression of narrow β-lactamases can play an important role in the development of CR in the absence of carbapenemases. Here, we investigated the role of avibactam, a potent β-lactamase inhibitor, in preventing the in vitro development of CR in a non-CP-Kpn.

Methods

We used SCL-1, a non-CP-Kpn strain recovered from the bloodstream of a patient that developed CR in vivo during treatment with imipenem (IMI). SCL-1 was exposed to serial passages of increasing concentrations of IMI alone [0.25-16 μg/mL] or in combination with avibactam (IMI-AVI) during 8 days. In the case of IMI-AVI, the concentration of AVI was fixed at 4 μg/mL. Evolution assays were performed in triplicate and considered 3 independent evolutionary lines (ELs). MICs at each time-point were measured to IMI and IMI-AVI by broth microdilution as per CLSI. Growth curves of SCL-1 and evolved strains were performed to assess fitness. The expression levels of narrow spectrum β-lactamases blaOXA-1,blaOXA-10, and of the ESBL blaCTX-M-15 were measured by RT-qPCR.

Results

In vitro exposure to IMI led to CR, with the MICs increasing from 0.5 μg/mL to 8 μg/mL in all 3 ELs. In contrast, all ELs exposed to IMI-AVI remained fully susceptible to IMI after 8 days, with a final MIC of 1 μg/mL. In addition, the MIC to IMI of the evolved, IMI-resistant strains, in the presence of AVI (4 μg/mL) dropped from 8 to 1 μg/mL. Growth curves revealed that IMI-resistant strains evolved in IMI alone exhibited a growth defect as compared to both SCL-1 and the susceptible strains evolved in IMI-AVI. Finally, compared to the SCL-1, the expression level of blaOXA-1 was significantly increased (p< 0.05) in all evolved isolates that developed IMI resistance (MIC=8 μg/mL). No significant changes were observed in the expression of blaOXA-10 and blaCTX-M-15 (Figure 1).Figure 1.RT-qPCR analysis of β-lactamase gene transcript levels for SCL-1 and evolutive lines (A and B). Data shown are individual data points with mean±SD superimposed.

Conclusion

Our findings suggest that the addition of AVI can prevent the in vitro development of IMI resistance in non-CP-Kpn. Our results have important implications for the clinical use of AVI as a strategy to combat CR in non-CP-Kpn infections.

Disclosures

All Authors: No reported disclosures
2189. Colistin Heteroresistance in Enterobacter due to Base Heterozygosity at Certain phoPQ Locations
Authors: Wang Chengcheng , Feng Yu , Zong Zhiyong
Published: November 2023

Background

Enterobacter species are major nosocomial pathogens, and the clinical implications and mechanisms of colistin heteroresistance (CHR) in Enterobacter remain unclear.

Methods

We used the population analysis profile (PAP) assay to determine the presence of CHR in Enterobacter. To examine whether CHR leads to treatment failure, we conducted in vitro time-killing assays and in vivo assays using murine intra-abdominal infection models. To determine the genetic mechanism for the CHR phenotype, we conducted whole-genome sequencing and ultra-deep second-generation sequencing.

A schematic outline of methods and main results

Results

In this study, we found that 30% of Enterobacter clinical strains causing bloodstream infections at West China Hospital exhibited CHR, which was associated with treatment failure and fatal infections, as demonstrated by in vitro time-kill tests and in vivo mouse infection modeling. We identified base alterations in the phoP-phoQ gene as the main resistance mechanism in Enterobacter CHR and that this heterogeneity originated from colistin selection and base heterozygosity, as detected by ultra-deep second-generation sequencing. We also found that several different resistance subpopulations existed simultaneously in the same strain with different resistance mechanisms.

Time-kill experiments in Enterobacter isolates with CHR or susceptible to colistin

CHR strains lead to in vivo colistin treatment failure

Phenotypic and genomic study of a CHR strain

Conclusion

We presented evidence for "genetic heterogeneity" in Enterobacter CHR strains, which is consistent with "phenotypic heterogeneity" and genetically explains the unstable and transient HR. This provides important insights and a fresh perspective into the mechanisms and clinical implications of Enterobacter CHR and underscores the importance of deep sequencing, prompting the research of high-throughput microbial single-cell sequencing as a method for detecting "genetic heterogeneity."

Frequency of bases that mediate colistin resistance at the same locus of phoP-Q in the parental and resistant strains

Disclosures

All Authors: No reported disclosures
2193. Vancomycin AUC:MIC Monitoring: Transitioning Safely from Inpatient to Outpatient Monitoring via OPAT
Authors: Campion Maureen , Aprile Richard , Troy Samantha , Tsuchida Yuran , Vindenes Tine
Published: November 2023

Background

Due to the increased availability of AUC:MIC calculators and evidence showing limited benefit to troughs greater than 15 mcg/mL, the 2020 IDSA/ASHP consensus vancomycin therapeutic guideline recommends AUC:MIC monitoring for patients with severe MRSA infections. At Tufts Medical Center (TMC) in Boston, MA, patients receive vancomycin dosed by AUC:MIC for severe MRSA infections or requiring greater than two weeks of therapy. There is limited information on transitioning these patients to the outpatient setting. Obtaining two appropriately timed levels in the rehabilitation, home infusion or nursing home setting can be extremely challenging. Therefore, at TMC, a correlating trough range associated with an AUC:MIC of 400-600 was calculated based upon patient specific parameters. This trough range was communicated to the outpatient parenteral antimicrobial therapy (OPAT) team for monitoring outpatient, reducing the need to draw 2 levels within the same dosing interval. The purpose of this study was to identify issues associated with transitions of care with vancomycin AUC:MIC monitoring and to identify potential solutions.

Methods

This was a retrospective review of patients receiving vancomycin dosed by AUC:MIC from September 2021 through March 2022. Patients who continued vancomycin with AUC:MIC monitoring on discharge were evaluated for challenges associated with their therapy by the OPAT coordinator. Data was collected on comorbidities, readmission to the hospital within 90 days, levels drawn incorrectly, patient non-compliance, need for re-education, and adjustment of therapy based on cultures.

Results

Seventy-two (72) patients received vancomycin monitoring by AUC:MIC at TMC. Of these patients, forty-two (42) were discharged with OPAT services. Twenty-six (26) of patients received intravenous vancomycin and sixteen (16) were prescribed other antibiotics. Twenty (20) patients planned for at least four weeks of outpatient therapy. The results of the outcomes of patients on therapy are listed in Table 1.

Conclusion

Our small study demonstrates AUC:MIC monitoring can be done safely and effectively in the outpatient setting. An emphasis should be placed on the education of the outpatient providers.

Disclosures

Maureen Campion, PharmD, shinoigi: Speaker
2203. ‘I always feel like, somebody's watching me’--Multimodal Antimicrobial Stewardship Supports Antibiotic Prescribing for Common Infections within the UNC Health Virtual Practice
Authors: Marx Ashley H , Mavrogiorgos Nikolaos , Barzin Amir
Published: November 2023

Background

Telehealth presents a new setting for antimicrobial stewardship interventions. Retrospective, disease-state-specific antibiotic review may be an effective mode of analyzing data and providing feedback to prescribers. The purpose of this project was to determine if prescriber-specific and composite team feedback were effective in maintaining adherence to preferred antibiotic selection and duration.

Methods

In July 2022, multimodal educational materials were distributed to UNC Health Virtual Practice providers to promote the use of preferred antibiotics and the shortest effective durations for common infections.

Encounter notes during the study period (6/1/2022 - 4/30/2023) were searched to determine eligible encounters corresponding urinary tract infections (UTI), skin and soft tissue infections (SSTI), pneumonia, and sinusitis. Eligible encounters with linked prescriptions were analyzed to determine whether antibiotic selection(s) and duration of therapy matched clinic-established best practices. The proportion of prescriptions corresponding to best practice for each infection type was calculated for each visit type, and for each provider.

Feedback consisted of provider-specific memos from the medical director on antibiotic selection and duration; composite team performance was shared with team members at provider meetings and senior leadership in administrative reports.

Results

The frequency of included visits was: sinusitis (393, 88%), SSTI (25, 6%), UTI (16, 4%), and pneumonia (11, 3%). The proportion of antibiotics corresponding to a firstline agent for each visit type were high for each included infection (range 72.6-100%; Table 1). Adherence to recommended duration of therapy was variable (range 12.5-100%). Six of 14 total prescribers had visits audited in both quarters. Among those, 5 of 6 increased or maintained personal performance from quarters 1 and 2 (Table 2).

Conclusion

Education followed by quarterly prescriber-specific and team feedback was associated with high rates of adherence to prescription of preferred agents. Use of the shortest effective duration of therapy presents additional opportunity for improvement. Targeted interventions for sinusitis provide the greatest stewardship opportunity for the UNC Health Virtual Practice. .

Disclosures

All Authors: No reported disclosures
2215. Impact of a Pharmacy-Driven Penicillin Allergy De-Labeling Pilot Program in Pre-Operative Cardiothoracic and Spine Surgery Patients at a Quaternary Hospital
Authors: Crum Hannah , Gagnon Brandon , Gens Krista
Published: November 2023

Background

Studies suggest up to 95% of patients with a reported penicillin (PCN) allergy can tolerate PCNs. Documented PCN allergies are associated with increased risks including Clostridioides difficile infections (CDI) and surgical site infections (SSIs). The goal of this study is to evaluate the effect of a pharmacist-driven PCN allergy de-labeling pilot program on the use of pre-operative beta-lactam antibiotics in cardiothoracic (CT) and spine surgery patients with documented PCN allergies.

Methods

This single-center, quasi-experimental study included adult patients with a charted PCN allergy and admitted for CT or spine surgery in 2021 (control group) and in the 6 months after the intervention pilot began (intervention group, 10/2022 - 03/2023). The primary outcome was rate of beta-lactam use peri-operatively. Secondary outcomes include SSI rates within 30 days after the operation, readmission rates within 30 days, CDI within 30 days of procedure, and hospital length of stay. In the intervention group, qualifying patients were interviewed via phone to assess allergy history. Chart documentation and allergy modification were completed to help ensure optimal antibiotic therapy. Qualified patients were de-labeled or referred to an allergist for outpatient skin testing and/or oral challenge.

Results

There were 214 patients in the control group and 72 in the intervention group. 57 (79.2%) patients in the intervention group were able to complete the interview. A total of 19 patients were referred to an outpatient allergist, and 7 were de-labeled (5 from pharmacist interview alone, 2 after allergist testing). Cefazolin was used pre-operatively in 91 (42.5%) of the control group vs. 55 (76.4%) of the intervention group (p< 0.001). There was no significant difference in SSI rate, 2.3% in the control group vs. 4.2% in the intervention group (p=0.286). No significant difference was noted in any other secondary outcomes except length of stay 3.65 days in the control group vs. 2.06 days in the intervention group (p = 0.0134).

Conclusion

The pharmacy-driven PCN allergy de-labeling pilot program in CT and spine surgery patients was associated with increased beta-lactam use. There was no significant difference in SSI rates; however, the study was underpowered to detect a difference.

Disclosures

All Authors: No reported disclosures