bluuebunny/crossref_metadata_2025 huggingface dataset:
1599. Real-World Efficacy of Long-Acting Cabotegravir and Rilpivirine in an Urban HIV Clinic
Authors: Perez Sarah , Petersen Elizabeth , Huhn Gregory
Published: November 2023

Background

Long-Acting cabotegravir/rilpivirine (LA-CAB/RPV) is the first FDA-approved, complete, long-acting injectable antiretroviral therapy (ART) regimen. In clinical trials, LA-CAB/RPV has proven to be highly effective in maintaining virologic suppression in people living with HIV (PLWH) with virologic suppression, on a stable ART regimen, and no resistance to either agent. There is limited published real-world data regarding the efficacy, adherence, and discontinuation rates of LA-CAB/RPV, especially in populations underrepresented or excluded from clinical trials. The purpose of this study is to evaluate the real-world efficacy of LA-CAB/RPV in achieving and maintaining virologic suppression in PLWH.

Methods

We conducted a single-center retrospective chart review of HIV-1 positive adults receiving care at the Ruth M. Rothstein CORE Center, a safety-net system in Chicago. Patients were included if they received at least one dose of LA-CAB/RPV between January 1, 2022 and October 31, 2022.

Results

A total of 96 patients met inclusion criteria and were included in the study. Of these patients, the median age was 42.5, 79.2% were Black/African American, 54.2% were cisgender men, and 46.9% had a BMI of ≥ 30 kg/m2. Baseline HIV viral load was < 50 copies/mL in 97.9% of patients. Additional baseline characteristics are described in Table 1. Most (86.5%) patients initiated direct-to-inject LA-CAB/RPV with 98% solely initiating every 2-month dosing schedule. The median number of LA-CAB/RPV doses received was 4 (range, 1-15). Virologic suppression was defined as HIV viral load < 50 copies/mL. Of the 96 patients, 79 had HIV viral load data at week 4 with 99.7% of those being undetectable, 37 had data at week 12 with 100% of those being undetectable, and 62 had data at week 24 of which 96.8% were undetectable. Adherence rates to injections were high, with 96.3% given on-time and the discontinuation rate was 18.8%

Conclusion

LA-CAB/RPV was highly effective in achieving and maintaining virologic suppression among a large number of patients at an urban HIV clinic. This study is limited by short follow-up time during the program's initial scale-up phase. Additional long-term data are needed to determine long-term real-world efficacy, adherence, and discontinuation rates.

Disclosures

Gregory Huhn, MD, MPHTM, Clinical Care Options: Advisor/Consultant|Eli Lilly: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Medscape: Advisor/Consultant|Merck: Advisor/Consultant|Practice Point Communications: Advisor/Consultant|Ridgeback: Grant/Research Support|Trio Health: Advisor/Consultant|Viiv: Advisor/Consultant|Viiv: Grant/Research Support
1600. Long-Acting Antiretroviral Injectable: Who Would Benefit?
Authors: Pogorzelski Karolina , Dandachi Dima , Hitchcock Nicole M , Fabricius Michela
Published: November 2023

Background

People with HIV (PWH) face many challenges in obtaining HIV care. Long-acting (LA)-injectable antiretroviral therapies (ART) can address some of these barriers. This project aimed to determine the percentage of patients who could receive the LA-injectable ART cabotegravir/rilpivirine (CAB/RPV) as an alternative to an oral daily pill regimen based on clinical indications.

Methods

We retrospectively reviewed medical records of adult PWH seen at the University of Missouri Health Care (MUHC) HIV outpatient clinic in Columbia, MO. We collected demographics, CD4 counts, hepatitis B status, HIV viral load, and HIV genotype resistance data. The primary endpoint was the percentage of PWH who would qualify to receive the LA-injectable ART CAB/RPV based on an undetectable HIV viral load, no documented chronic hepatitis B status, and no resistance to either CAB or RPV based on the Stanford University HIV Drug Resistance Database.

Results

Six hundred and twenty-five unique PWH were receiving care at MUHC with a median age of 49 years old, 20% female, 27.5% Black/African American, 4.8% Hispanic and/or Latino, and 9.1% with AIDS (CD4 count < 200 cells/uL). 17.9% of PWH were not eligible for the LA-injectable ART CAB/RPV due to a detectable HIV viral load (defined as > 50 copies/mL on the last HIV viral load result). An additional 7.2% did not qualify due to having a genotype resistance to CAB or RPV and 1.8% did not qualify due to having chronic hepatitis B. Altogether, 151 PWH (24.2%) had one or more clinical contraindications for the LA-injectable ART CAB/RPV based on current guidelines. Genotype resistance testing was not available for 59.6% of PWH. However, out of the 474 PWH who are eligible to receive the LA-injectable ART CAB/RPV, only 76 (16.1%) are currently in care and on this regimen.

Conclusion

In this study, we identified a high percentage of patients with no available genotype and a low uptake of the new LA-injectable ART CAB/RPV. To optimize the use of the the LA-injectable ART CAB/RPV and to make it accessible to PWH who could benefit from it, further research needs to be done using both quantitative and qualitative measures to identify barriers and facilitators at the patient, provider, and system level and to develop effective implementation strategies.

Disclosures

Dima Dandachi, MD, MPH, ContraFect Corporation: Grant/Research Support|Missouri Foundation for Health: Grant/Research Support|ViiV healthcare: Grant/Research Support|ViiV healthcare: Honoraria
1601. Transmitted Drug Resistance in Treatment-Naïve People Living with HIV in Costa Rica
Authors: Ramirez-Cardoce Manuel , Lopez-Bolanos Viviana
Published: November 2023

Background

Transmitted drug resistance (TDR) occurs in people living with HIV infection (PLWH) who are not exposed to antiretroviral drugs but who are infected with a virus with mutations associated with resistance. In Costa Rica, HIV genotyping is performed in PLWH failing their first-line ART regimen, but it is not routinely done for all treatment-naïve PLWH before ART initiation, therefore, little is known about TDR prevalence.

Methods

The aim of this study was to determine the prevalence of TDR and the HIV mutation patterns. During 2020, 162 cases of newly diagnosed treatment-naïve PLWH from all of the country’s HIV clinics were included for a genotyping study. Viral ARN was extracted from plasma samples obtained from the HIV National Reference Laboratory and protease (PR), reverse transcriptase (RT), and integrase (IN) regions were amplified and sequenced. The HIV database Program (Stanford University) and the World Health Organization (WHO) 2009 TDR surveillance mutation list were used for interpretation of resistance-associated mutations.

Results

The overall prevalence of TDR was 36% (N=59/162). According to ART class, TDR was 22% in the nucleoside reverse transcriptase inhibitors (NRTI), followed by 13% in the non-nucleoside reverse transcriptase inhibitors (NNRTI); for the protease inhibitors (PI) and the integrase inhibitors (INI), TDR was 8% and 3%, respectively. (Figures 1-3). Most common mutations were: in NRTI, M41L (9.9%), and M184I (6.8%); in NNRTI, K103N (7.4%); in PI, M46I (4.3%); in INI, T97A (1.9%). (Table 1). The median age was 32 years-old (range: 16-71), and 91% were male. Median CD4 count was 420 cells/uL (range: 11-1670) and median viral load was 588337 copies/mL (range: 1220-10000000). According to CDC classification, 20% were stage C-3.

Source: local database

Source: local database

Source: local database

Conclusion

This study population has a moderate level of HIV drug resistance (HIVDR) in ART-naïve PLWH and strongly implies the need to introduce HIVDR surveillance in Costa Rica. These findings confirm the TDR and highlight the need for systematic viral load monitoring and drug resistance testing at diagnosis. Continuous surveillance of newly infected individuals is required to help strategize the best ART regimen for these patients, and should prompt a change in current local recommendations for starting ART.

Source: local database

Disclosures

All Authors: No reported disclosures
1603. Efficacy, safety and tolerability of switching to dolutegravir/lamivudine in virologically suppressed adults living with HIV on bictegravir/emtricitabine/tenofovir alafenamide -the DYAD study
Authors: Rolle Charlotte-Paige M , Castano Jamie , Nguyen Vu , Hinestrosa Federico , DeJesus Edwin
Published: November 2023

Background

In TANGO, switching to dolutegravir/lamivudine (DTG/3TC) was noninferior compared to continuing a tenofovir alafenamide (TAF)-based regimen, however switching from bictegravir (BIC)/emtricitabine (F)/TAF was not evaluated. Here, we present efficacy and safety of switching to DTG/3TC compared with continuing B/F/TAF in virologically suppressed adults through 24 weeks.

Methods

DYAD (NCT04585737) is an ongoing, open-label clinical trial that randomized adults with HIV-1 RNA< 50 copies/mL and no prior virologic failure (2:1) to switch to once-daily fixed-dose DTG/3TC or remain on B/F/TAF. The primary endpoint is the proportion with HIV-1 RNA ≥ 50 c/mL at Week (W) 48 (FDA snapshot algorithm, ITT-E population). A planned W24 interim analysis assessed noninferiority with a 6% margin.

Results

Overall, 222 adults (16% women; 51% aged ≥50 years; 28% Black) were randomized. At W24, 3 (2%) participants on DTG/3TC and 3 (4%) on B/F/TAF had HIV-1 RNA ≥ 50 c/mL (adjusted treatment difference -2.1%, 95% confidence interval [-9.5%, 2.5%]) meeting noninferiority criteria. Through W24, 4 on DTG/3TC and 3 on B/F/TAF met confirmed virologic withdrawal (CVW) criteria and underwent resistance testing. 2/7 had treatment-emergent resistance. One B/F/TAF CVW developed M184M/I and G140G/S at W12; at study discontinuation (DC), HIV-1 RNA< 50 c/mL and the participant remained on B/F/TAF. One DTG/3TC CVW had no resistance on study genotype but underwent repeat genotypic testing outside the study (ordered by clinic provider) and had M184V at W12; at study DC, HIV-1 RNA< 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG + darunavir/cobicistat (DRV/c). One non-CVW DTG/3TC participant developed M184V and K65R at W12 (genotype inadvertently collected at first episode of unconfirmed viremia); at study DC, HIV-1 RNA< 50 c/mL on DTG/3TC and the participant was subsequently transitioned to DTG+DRV/c. Drug-related adverse events (AEs) and withdrawals due to AEs occurred in 31 (21%) and 6 (4%) participants with DTG/3TC and 1 (1%) and 0 participants with B/F/TAF, respectively.

Conclusion

DYAD demonstrated noninferior efficacy of switching to DTG/3TC vs. continuing B/F/TAF at W24. Higher AE rates in the DTG/3TC arm are likely consistent with the open-label nature of this switch study.

Disclosures

Charlotte-Paige M. Rolle, MD, MPH, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Advisor/Consultant|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria Federico Hinestrosa, MD, AbbVie: Honoraria|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Honoraria|MSD: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Edwin DeJesus, MD, Gilead Sciences, Inc: Advisor/Consultant|Theratechnology: Advisor/Consultant|Theratechnology: Honoraria
1606. Dual Trajectories of Antiretroviral Therapy Adherence and Polypharmacy in Women with HIV in the United Sate
Authors: SAEED A B U B A K E R , Ghebremichael Musie , Konkle-Parker Deborah , Weiss Deborah Jones , Collins Shelby , Adimora Adaora A , Schneider Michael F , Cohen Mardge H , Tamraz Bani , Plankey Michael , Wilson Tracey , adedimeji Adebola , Haberer Jessica , Jacobson Denise L Jacobson
Published: November 2023

Background

Polypharmacy using five or more medications with antiretroviral therapy (ART) may increase the risk of nonadherence to prescribed treatment. We aimed to identify the interrelationship between trajectories of adherence to ART and polypharmacy.

Methods

We included women with HIV (aged >18 years) enrolled in the Women's Interagency HIV Study in the United States from 2014-2019. We used group-based trajectory modeling (GBTM) to identify trajectories of adherence to ART and polypharmacy and dual GBTM to identify the interrelationship between adherence and polypharmacy.

Results

Overall, 1538 were eligible (median age of 49 years). GBTM revealed five latent trajectories of adherence with 42% of women grouped in the consistently moderate trajectory. GBTM identified four polypharmacy trajectories with 45% categorized in the consistently low group.

Conclusion

The joint model did not reveal any interrelationship between ART adherence and polypharmacy trajectories. Future research should consider examining the interrelationship between both variables using objective measures of adherence.

Disclosures

Jessica Haberer, MD, MS, Merck: Advisor/Consultant
1612. Correlates of Sustained Viral Suppression among HIV-Positive Adults Receiving Antiretroviral Therapy from Six Secondary Health Facilities in Northern Nigeria.
Authors: TSIGA-AHMED F A T I M A H I , Musa Muhammad S , Sulaiman Abdulwahab K , Jalo Rabiu I , Bako Abdulaziz T , Sulaiman Sahabi K
Published: November 2023

Background

Sustained viral suppression in HIV is essential to minimize drug resistance, reduce secondary transmission and improve health outcomes necessary to achieve the UNAIDS 95-95-95 strategy. There is dearth of information on viral suppression among adults in Nigeria. Identifying correlates of sustained viral suppression will inform treatment guidelines especially for people at risk and provide recommendations to policy makers.

Methods

We collected sociodemographic and HIV-related data from a cross-section of 730 HIV-positive adults receiving antiretroviral therapy from six secondary health facilities in northern Nigeria, between October 2021 and February 2022. Sustained viral suppression was defined according to the Nigerian National Guideline for HIV Prevention, Treatment and Care as a viral load below the detection threshold of less than 20 copies of HIV RNA/ml. Proportion of participants with sustained viral suppression was estimated and a multivariable analysis used to identify independent correlates of sustained viral suppression.

Results

The sustained viral suppression rate among HIV-positive adults on ART was 35.7% [95% CI: 32.2, 39.5]. Being married [AOR 2.01; 95% CI: 1.34, 3.03] and having secondary education [AOR 0.43; 95% CI: 0.26, 0.74] were significantly associated with sustained viral suppression. Respondents on treatment for 5-10 years [AOR 1.76; 95% CI: 1.17, 2.64] and those taking two or more pills [AOR 5.67; 95% CI: 3.74, 8.62] were more likely to have sustained viral suppression. Previous treatment for opportunistic infection [AOR 0.24; 95% CI: 0.15, 0.41] significantly decreased the likelihood of sustained viral suppression.

Conclusion

Sustained viral suppression rates among HIV-positive adults on ART in the six facilities were suboptimal. While being married, taking two or more ART pills and being on treatment for 5-10 years increased the likelihood of having a suppressed viral load, being educated up to secondary level and previous treatment for opportunistic infection decreased the odds of having sustained viral suppression. There is a need to improve viral load monitoring and direct viral suppression interventions towards at risk population.

Disclosures

All Authors: No reported disclosures
1613. Frailty is Associated with Intestinal Barrier Dysfunction in Aging People Living with HIV
Authors: xu xiaolei , Yan Jiangyu , Lu Yanqiu , Yang Mengru , ouyang jing , Chen yaokai
Published: November 2023

Background

Recent evidence indicates that frailty is prevalent in PLWH compared to those without HIV, especially in the elderly population. However, the underlying mechanisms fundamental to this phenomenon reman unclear. Gut damage and increased microbial translocation are hallmarks of HIV infection, and are known to promote and perpetuate the chronic systemic inflammation seen in PLWTH. Meanwhile, it has been observed that chronic inflammation also contributes to the frailty. Herein, we investigate the association between frailty and intestinal barrier dysfunction in PLWH.

Methods

This cross-sectional study was designed to assimilate and analyze clinical data and results of blood samples in PLWH. According to frailty phenotype assessment, participants were stratified into three groups comprising a frailty, a pre-frailty, and a non-frailty group. We subsequently measured the levels of biomarkers of gut damage, microbial translocation, and levels of inflammatory cytokines to assess the relationship between these biomarkers and frailty.

Results

One hundred and fifty one PLWH over 50 years of age were involved in this study, and were stratified into three groups: 73 patients in the non-frailty group, 61 patients in the pre-frailty group, and 17 patients in the frailty group. Their incidence of anxiety, depression, and stress was calculated to be higher in the frailty group than other two groups (p< 0.05). The concentration of gut damage biomarkers in serum, i.e., levels of regenerating islet-derived protein-3α (REG-3α) and intestinal fatty acid-binding protein (I-FABP), showed significant positive correlations with frailty, and was observed to be highest in the frailty group. On the contrary, no significant association was observed between the hematological biomarkers of microbial translocation with frailty. Additionally, IL-6, IP-10, and TNF-α concentrations in plasma were found to positively correlate with frailty in aging PLWH (i.e., these biomarkers had the highest concentrations in the frailty group).

Conclusion

Our study revealed that the inflammation induced by gut damage may contribute to frailty in elder PLWH.

Disclosures

All Authors: No reported disclosures
1614. Efficacy and Safety of Adjusted Renal Dosing of Tenofovir DF Versus Abacavir Switching in HIV Patients with Decreased Glomerular Filtration Rate After Receiving Tenofovir DF-Based Regimen
Authors: Yamasmith Eakkawit , Sirijatuphat Rujipas , Ratanasuwan Winai , Werarak Peerawong
Published: November 2023

Background

A switch from tenofovir disoproxil fumarate (TDF) to abacavir (ABC)-based therapy is one of treatment options for HIV-infected patients with decreased glomerular filtration rate (eGFR) after receiving a TDF-based regimen. However, ABC may not be available in some hospitals in Thailand. TDF dose reduction showed a significant improvement of eGFR without virological failure. This study aimed to compare the efficacy and safety of TDF dose reduction versus ABC switching for the treatment of patients with decreased eGFR after receiving TDF.

Methods

This open-label, randomized, non-inferiority study was conducted at Siriraj Hospital, Thailand, during March 2019 to May 2021. Eligible participants were HIV-suppressed patients aged ≤18 years with decreased eGFR (eGFR 30-60 mL/min by Cockcroft-Gault equation) after receiving TDF-based therapy. Patients were randomized (1:1 by block of four) to a TDF dose-adjusted regimen or an ABC-based regimen. The primary outcome of study was the change in eGFR at 24 weeks after regimen modification. The non-inferiority margin was -12 mL/min. Other outcomes were the virological efficacy and safety at 24 weeks after regimen modification.

Results

30 patients were enrolled (15 patients in the TDF dose-adjusted regimen group and 15 patients in the ABC-based regimen group). The distribution of age, sex, CD4 count, serum creatinine, eGFR and duration of TDF treatment were similar between both groups. The mean change of eGFR (SD) at 24 weeks after regimen modification were +1.87 (7.90) mL/min in the TDF dose-adjusted regimen group and +15.64 (6.53) mL/min in the ABC-based regimen group (P< 0.001). The difference of mean change of eGFR between both groups at 24 weeks was -13.77 mL/min (95% CI; -20.18 to -7.36 mL/min) (P< 0.001). The sustained viral suppression was observed in both groups. Two patients in the TDF dose-adjusted regimen group developed progressive kidney impairment and one of them developed Fanconi syndrome.

Baseline Characteristics

Outcomes

Conclusion

The TDF dose-adjusted regimen demonstrated the efficacy in improving eGFR but this regimen did not prove non-inferiority over the ABC-based regimen. The progression of kidney dysfunction should be cautioned in patients who received the adjusted renal dosing of TDF.

Disclosures

Eakkawit Yamasmith, Police General Hospital: Advisor/Consultant
1615. Efficacy of Long-Acting Cabotegravir and Rilpivirine in a Diverse Group of Patients in a Real-World Setting
Authors: Yared Nicholas F , Gudipati Smitha , Payne Shannon , Alvi Rija B R , Cherian John , Lodivico John Di , Markowitz Norman , Brar Indira
Published: November 2023

Background

Cabotegravir (CAB) + rilpivirine (RPV) is the first recommended complete long-acting (LA) regimen for maintenance of HIV-1 virologic suppression. The efficacy and safety of switching to CAB + RPV LA (CAR) has been shown in clinical trials. CAR injections offer less frequent dosing and address issues of adherence and disclosure related to daily oral cART. We describe the clinical characteristics and outcomes of switching a diverse group of people with HIV (PWH) to CAR in a real-world setting.

Methods

A retrospective cohort study was performed to assess virologic efficacy of intramuscular CAR given every 4 or 8 weeks among adult PWH receiving care at Henry Ford Health ID Clinic by an interdisciplinary team of physicians, nurses, social workers, and a pharmacist. Efficacy was defined as HIV-1 RNA < 20 copies/mL at 3 months. Demographics, clinical characteristics, and outcomes were extracted from the electronic medical record.

Results

We included the first 51 patients to receive CAR. Median age was 46 years (IQR 34 -59). Black individuals were 75%, cisgender males 84%, and transgender females 3.9% of participants. PWH were diagnosed a median of 12 years ago (IQR 11-17). At time of switch, 90% had HIV viral load (VL) < 20 copies/ml, and 9.8% of patients were viremic with < 75 copies/ml. Mean Cd4+ cell count was 871 cells/µL (IQR 632-1603). Prior to switch, 80% had received ≥ 2 cART regimens, 75% had INSTI exposure, and 45% had NNRTI exposure. Among 38 patients with HIV-1 genotypes available prior to switch, 4 had either baseline NNRTI or INSTI mutations (Table 2). For patients with VL data at 3 months, 37 of 38 (98%) had an undetectable VL. Virologic failure occurred in 1 PWH with BMI 35 who had a Y188L RT mutation in a 2009 genotype which did not include RPV (2011 approval), with subsequent emergence of pan-NNRTI and INSTI resistance.

Conclusion

A high degree of virologic suppression at 3 months was achieved among an older, diverse cohort of PWH cared for by an interdisciplinary team. Unrecognized baseline HIV resistance to NNRTI contributed to one virologic failure. It is important to assure that genotypic susceptibility interpretations are current and to carefully assess for eligibility before switching to CAR.

Disclosures

John Di Lodivico, PharmD, Midwest AIDS Training & Education Center: Honoraria|ViiV Healthcare: Advisor/Consultant|Wayne State University: Honoraria Indira Brar, MD, Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Gilead: Honoraria|Janssen: Grant/Research Support|Janssen: Honoraria|ViiV: Advisor/Consultant|ViiV: Grant/Research Support|ViiV: Honoraria
1617. Assessment of Bloodstream Infections in Patients with Intrapartum Fever
Authors: Kamel Barbara , Doan Thien-Ly , Luchana Vidal , Oppenheim Michael , Donaghy Henry
Published: November 2023

Background

The American College of Obstetricians and Gynecologists (ACOG) offers guidance on the management of intraamniotic infections, where the diagnosis of chorioamnionitis can be made based on clinical criteria (e.g., maternal leukocytosis, purulent cervical drainage, or fetal tachycardia), positive amniotic fluid analysis (gram stain, glucose level, cultures), or placental pathology. No recommendations for blood cultures are made. The study purpose is to evaluate the utility of blood cultures in the management of intrapartum fever and to analyze the microbiological data.

Methods

This is a retrospective, descriptive study that analyzes patients with blood cultures drawn within 5 days of delivery from 1/2019 to 12/2022. Procurement contaminants were excluded from the analysis. Chart reviews were conducted on the positive cultures. Data collected included age of mother, gestational age, method of delivery, presence of fetal tachycardia, cultures sent prior to admission, maternal Group B Streptococcus (GBS) status, culture results including organism (blood, placenta cultures), and antimicrobials administered. Descriptive statistics were utilized.

Results

Of the 70,540 deliveries in the study period, there were a total of 507 patients had blood cultures drawn, of which 25 were positive. Three patients were excluded because they were deemed to be procurement contaminants (e.g., 2 patients with coagulase-negative Staphylococcus species and 1 patient with Micrococcus species). Analysis of the bloodstream infection were performed on 22 patients, thus the rate of bacteremia was 4.3% in our cohort. The mean age was 33.3 ± 4.4 years with an average gestational age at birth of 32.3 ± 6.5 weeks. Of the 22 patients, 19 (86.4%) received a cesarean section and 4 (18.2%) were positive for GBS. The most common pathogen present were E. coli (45.5%) and Prevotella bivia (13.6%). The most common antimicrobials given were ertapenem (63.6%), followed by clindamycin + gentamicin (13.6%).

Organisms Isolated from Blood Cultures

E. coli was the predominant organism isolated, followed by Prevotella. Interestingly, Candida was isolated in 1 patient where empiric ertapenem or gentamicin + clindamycin would not have been sufficient.

Conclusion

Although uncommon, bacteremia can occur in patients with intrapartum fevers. Gram-negative and anaerobes were found to be most common organisms. Bloodstream infections may require a longer duration of treatment therefore blood cultures should be considered as part of the work-up of intrapartum fever.,

Disclosures

All Authors: No reported disclosures
1620. Identification of plasma biomarkers of neurological complications in patients with congenital cytomegalovirus infection by proteome analysis
Authors: Yamaguchi Makoto , Suzuki Takako , Kidokoro Hiroyuki , Iwada Ken-ichi , Fukuda Yuto , Haruta Kazunori , Torii Yuka , Ito Yoshinori , Kawada Jun-ichi
Published: November 2023

Background

Congenital cytomegalovirus infection (cCMV) is the leading cause of non-hereditary sensorineural hearing loss and can cause other long-term neurodevelopmental disabilities. To consider antiviral treatment, it is important to differentiate between symptomatic and asymptomatic patients by early infancy. However, it is difficult to identify neurological complications in some cases. This study aimed to identify candidate plasma biomarkers for neurological complications of cCMV during the neonatal period using proteome analysis.

Methods

This study retrospectively enrolled five patients with asymptomatic cCMV and nine patients with symptomatic cCMV, including those with hearing loss and/or abnormal brain imaging. Plasma samples were obtained during the neonatal period. After extraction of 14 high-abundant proteins from the plasma, proteins were digested by trypsin. The peptides were analyzed by liquid chromatography–mass spectrometry using an Orbitrap Fusion mass spectrometer. Protein quantification was performed using Proteome Discoverer. Levels of differently expressed proteins were validated by enzyme-linked immunosorbent assay.

Results

In total, 456 proteins were identified and quantified. Levels of 65 proteins were significantly higher in patients with symptomatic cCMV than in those with asymptomatic cCMV. The top two enriched categories for these proteins according to pathway enrichment analysis were “complement and coagulation cascade” and “inflammatory response.” In contrast, levels of 30 proteins were significantly higher in patients with abnormal brain imaging. Plasma levels of fms-related receptor tyrosine kinase 4 (FLT4) were significantly higher in patients with symptomatic cCMV than in those with asymptomatic cCMV. Moreover, levels of plasma peptidylprolyl isomerase A (PPIA) were significantly higher in patients with abnormal brain imaging than in those without.

Conclusion

Proteome analysis showed that the proteins related to inflammatory response pathways were upregulated in patients with symptomatic cCMV. FLT4 and PPIA can be used as novel diagnostic biomarkers for neurological complications of cCMV to enable early therapeutic intervention with antiviral agents.

Disclosures

All Authors: No reported disclosures
1622. Increase in Congenital Toxoplasmosis and Acute Toxoplasmosis Among Pregnant Women in the US during the COVID-19 pandemic
Authors: Contopoulos-Ioannidis Despina , Bonetti Valerie , Montoya Jose G
Published: November 2023

Background

During the COVID19 pandemic a rise in diverse opportunistic infections has been described

Methods

In this retrospective cohort study, we analyzed the trajectory of new congenital toxoplasmosis (CT) cases and cases of acute toxoplasmosis among pregnant women (AT-P) during the COVID19-pandemic (2020-2022) compared to a pre-pandemic period (2000-2019). We perused data from the Remington’s Laboratory, the National Reference Laboratory for Toxoplasmosis in the US. We calculated the yearly number of cases of CT and AT-P; the incidence rate (IR) of CT and AT-P (IR=number of cases/total number of children < 12 months or pregnant women respectively tested by the Toxoplasma IgG-Dye test). We used ARIMA time-series models to compare the trajectory slopes between the two periods.

Results

In the pre-pandemic period there were 196 CT cases among 8194 tested children< 12 months and 814 AT-P cases among 33,345 pregnant women. The respective numbers during the pandemic were 43 CT among 1833 tested children < 12 months and 65 AT-P among 1983 pregnant women. In 2022 we had the largest number of CT cases (21 CT in 2022 vs 6 in 2019) and similarly a high number of AT-P cases (22 AT-P in 2022 vs 16 in 2019)(Fig 1). This increase occurred, despite a drop in the total number of samples tested in the Lab ≥2020, due to programmatic changes in one major Lab client (Fig 2). The yearly IR of CT increased during the pandemic, from 1.05 cases/100 tested (6/574) in 2019 to 3.71 cases/ 100 tested (21/566) in 2022. The yearly IR of AT-P also increased during the pandemic, from 1.35 cases/ 100 tested (16/1183) in 2019 to 3.79 cases/100 tested (22/580) in 2022 (Fig 3). There was a positive trajectory-slope trend in CT and AT-P during the pandemic. This occurred after a preceding negative trajectory-slope trend in AT-P in the pre-pandemic period.Figure 1:Number of Congenital Toxoplasmosis and Acute Toxoplasmosis during Pregnancy cases: 2000-2022Figure 2:Toxoplasmosis IgG Dye tests in Pregnant Women and in Children <12 months of age: 2000-2022Figure 3:Incidence Rates of Congenital Toxoplasmosis (IR-CT)and Acute Toxoplasmosis During Pregnancy (IR-AT-P): 2000-2022

Conclusion

During the pandemic, there was a rising trend in CT and AT-P cases diagnosed in the National Reference Lab for toxoplasmosis in the US. In 2022 there was a peak in the CT cases. The etiology remains unclear. A possible increase- during the lockdowns-in the contact of pregnant women with cats and/or a possible limited prenatal-preventive-guidance during the pandemic due to possible disruption in prenatal care services, could have been contributing factors. These trends need further monitoring.

Disclosures

All Authors: No reported disclosures
1627. Antibiotic Use and Clinical Outcomes in Peripartum Infections
Authors: Siegrist Emily A , Sassine Joseph
Published: November 2023

Background

Peripartum infections are a leading cause of maternal morbidity and mortality. Historically, these infections have been treated with combinations of ampicillin and gentamicin with or without clindamycin. However, resistance in anaerobic and gram-negative bacteria to these antimicrobials has been increasing nationally. There is limited modern data evaluating the incidence and outcomes of chorioamnionitis and endometritis, especially in the context of modern resistance patterns and antibiotic regimens.

Methods

This is a single-center, retrospective study at an academic medical center. The primary objective is to describe antibiotic use and outcomes in patients diagnosed with chorioamnionitis or endometritis. Patients were identified by ICD codes using Vigilanz software. Patients with a coded diagnosis for chorioamnionitis or endometritis in 2022 were included and stratified according to highest level of care. Chi-square and Fisher’s exact test were used for categorical variables, Mann-Whitney test for continuous variables.Table 1Baseline DemographicsTable 2Pregnancy and Delivery Characteristics

Results

We included 176 patients, indicating 4.6% of deliveries were complicated by a peripartum infection. Seven patients (4%) required ICU level of care. These patients were more likely to be multiparous, have longer time from rupture of membranes to delivery, have vaginal discharge, and had more pronounced leukocytosis with left shift. The most common organism isolated was Escherichia coli and only piperacillin-tazobactam (TZP) was active against all isolates. Patients admitted to the ICU were more likely to have received metronidazole, TZP, vancomycin or a cephalosporin, to have switched antibiotics and to have longer days of therapy. Only one patient from the ICU group passed away for causes unrelated to the infection.Table 3Peripartum Infection CharacteristicsTable 4Peripartum Infection ManagementTable 5Outcomes

Conclusion

Peripartum infections are common, and most patients improve on short courses of clindamycin, gentamicin, and ampicillin. Historical antibiotic regimens may not have desired activity against E. coli isolates, and clinicians may consider use of TZP for patients failing to improve on standard therapy. Larger studies are needed to establish a more specific diagnosis, validate risk factors for severity, and explore the efficacy of updated antimicrobial regimens.

Disclosures

All Authors: No reported disclosures
1638. Development of a Model to Estimate Persistence of hSBA Titers Over Time Following a Primary Series and Booster Dose of the Pentavalent Meningococcal MenABCWY Vaccine
Authors: Cai Bing , Peyrani Paula , Beeslaar Johannes , Maguire Jason , Maansson Roger , Palmer Paul
Published: November 2023

Background

Serogroups A/B/C/W/Y cause nearly all meningococcal disease. Therefore, comprehensive protection requires vaccination against all 5 serogroups. A pentavalent MenABCWY vaccine, composed of 2 licensed vaccines (MenB-fHbp, MenACWY-TT), is undergoing clinical development in adolescents and young adults. We predicted persistence of serum bactericidal activity against human complement (hSBA) titers 5 years after both a MenABCWY primary series and booster dose using a power law model (PLM).

Methods

The PLM was fitted with hSBA data from a previous MenABCWY clinical trial (NCT03135834) assessing a 2-dose primary regimen (0, 6 months), immunopersistence 4 years post primary, and booster vaccination given observed titers in healthy 10–25-year-olds. The PLM was then used to predict hSBA titers against test strains up to 5 years after the primary series and up to 5 years after a booster dose. The hSBA lower limit of quantitation (LLOQ) was 1:16 for the A22 MenB strain and 1:8 for all other test strains.

Results

The PLM-predicted hSBA titers were consistent with those observed after a 2-dose MenABCWY primary series and a booster dose, which was given 4 years after the primary series (Figure 1–2). At 5 years post primary series, the percentage of individuals with hSBA titers ≥ LLOQ was predicted to range from 63.4%‒100% for MenA/C/W/Y strains and 8.0%–26.8% for MenB strains. Five years after the booster dose, the PLM predicted that 97.0%–100% and 45.7%‒88.6% of individuals had MenA/C/W/Y and MenB hSBA titers ≥ LLOQ, respectively.

Conclusion

The PLM supports that persistence of MenA/C/W/Y and MenB antibody responses after primary MenABCWY vaccination are maintained to at least 5 years. At 5 years after the booster dose, a substantial percentage of adolescents and young adults are predicted to have protective hSBA titers against all 5 serogroups.

Funding: Pfizer Inc

Disclosures

Bing Cai, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Paula Peyrani, MD, Pfizer, Inc: Employee|Pfizer, Inc: Stocks/Bonds Johannes Beeslaar, MD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Jason Maguire, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Roger Maansson, MS, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Paul Palmer, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds
1641. Prescribing and Dispensing Delayed Antibiotics to Pediatric Patients with Acute Otitis Media and Pharyngitis
Authors: Balasubramaniam Shobhitha , Melanie Melanie , Fitzpatrick Eleanor , Hurley Katrina , Black Emily
Published: November 2023

Background

Delayed antibiotic prescriptions with instructions to wait a defined period of time before filling the prescription is a strategy often used to decrease the unnecessary use of an antibiotic. Although "watchful waiting" for illnesses, such as acute otitis media (AOM) and pharyngitis, that are suspected of being viral is recommended, little is known about how often delayed antibiotics are prescribed at our institution. The primary objectives of this study were to characterize delayed prescriptions for pediatric patients with AOM or pharyngitis and to assess each prescription for adherence to guidelines.

Methods

Design: This study was a retrospective chart review. Pediatric patients with AOM and pharyngitis assessed and discharged from the Emergency Department (ED) between March 1, 2019 to February 28, 2021 were considered for inclusion. Data were collected from the ED Treatment Record by a trained research assistant.

Setting: Our study was completed in a pediatric ED at a tertiary hospital in Canada.

Exposures or interventions: Patients prescribed a delayed antibiotic on discharge from the ED.

Main Outcome Measures: Frequency of delayed antibiotic prescribing, proportion of antibiotic prescriptions adherent to guidelines for empiric choice, dose, and duration. Adherence to guidelines was assessed using local guidelines and position statements by the Canadian Pediatric Society as the gold standards.

Statistical analysis: Data were entered in REDCap and exported to excel for descriptive analysis.

Results

Delayed antibiotics were prescribed to 21.2% (332/1563) of patient encounters during the study period. Amoxicillin was the most commonly prescribed antibiotic (88.6%, 294/332). The majority of delayed prescriptions were prescribed for AOM (77.7%, 258/332). Most patients (94.8%, 309/326) received a delayed prescription for an empiric antibiotic that adhered to guidelines. Fewer prescriptions adhered to guidelines for dose (75.8 %, 247/326) and duration (73.6%, 240/326).

Conclusion

Most patients received the appropriate empiric antibiotic to treat AOM and pharyngitis however, dose and duration of use may be improved through antimicrobial stewardship initiatives.

Disclosures

Emily Black, BSc(Pharm), PharmD, Drug Evaluation Alliance of Nova Scotia: Grant/Research Support|Research Nova Scotia: Grant/Research Support
1647. Clinical Outcomes in Pediatric Appendectomy Patients Treated with Piperacillin-Tazobactam versus Ceftriaxone/Metronidazole
Authors: Cosimi Reese , Daragjati Florian , Ward Sasha , Whitmore Maria , Marisol Fernandez , Moreno Ana Cristina Perez , Miller Collin , Fakih Mohamad G
Published: November 2023

Background

Appendicitis is the most common cause of emergent pediatric surgeries. The standard treatment includes surgical removal of the appendix plus or minus antibiotic therapy. Piperacillin-tazobactam or ceftriaxone/metronidazole are commonly utilized antibiotic regimens. While the latter option may be preferable for antimicrobial stewardship measures due to its narrower spectrum of activity, current existing evidence is conflicting as to whether one results in improved clinical outcomes.

Methods

Retrospective cohort study across four regionally diverse pediatric hospitals of all admitted patients aged 0 to 17 years with a procedure code for appendix resection between January 1, 2021 to December 31, 2022. Patients were included if they received either piperacillin-tazobactam or ceftriaxone/metronidazole during the encounter corresponding to the appendectomy procedure. Outcomes measured include length-of-stay (LOS) and 30-day readmission.

Results

A total of 600 appendectomy cases were included in the analysis of which 463 received ceftriaxone/metronidazole and 137 patients received piperacillin-tazobactam. Patients aged < 10 years old were more likely to receive piperacillin-tazobactam. More perforated appendicitis cases were noted in the patients who received ceftriaxone/metronidazole. Average LOS in days (standard deviation) was not different between the two groups, 4.2 (6.1) and 3.9 (6.3), respectively (p=0.25). Readmissions were more common in the patients who received piperacillin-tazobactam, 3.2% and 7.3% (p=0.04).

Conclusion

Clinical outcomes in pediatric appendectomy patients do not appear to be associated with antibiotic regimen selection. Our study supports the continued use of ceftriaxone/metronidazole first line for appendicitis treatment in children taking into account local susceptibility patterns.

Disclosures

Reese Cosimi, PharmD, Allergen: Advisor/Consultant
1648. Impact of a Pediatric Antimicrobial Stewardship Program on Optimizing Antibiotic Usage in a Non-Freestanding Children’s Hospital (PEDS-ASP)
Authors: Siu Anita , Barron Linda , Kohute Michelle , Rawstron Sarah A , Eller Amy A , Cruz Liliana , Cruz Mariawy Riollano
Published: November 2023

Background

Antibiotic misuse can lead to poor patient outcomes, including ineffective treatment of infections, increased adverse effects, and development of antibiotic resistance. Implementing an antimicrobial stewardship program (ASP) is a vital strategy to improve and measure the appropriate use of antibiotics. This study aimed to assess the impact of pediatric ASP implementation on the reduction of restricted antibiotic usage and the improvement of patient outcomes.

Methods

A single-center retrospective-prospective study was conducted at a children’s hospital and included patients admitted to general pediatric or pediatric intensive care units receiving one or more restricted antibiotics. Prior-authorization of these restricted antibiotics was implemented as the ASP strategy. A three-month pre- and post-implementation chart review was completed. The primary outcome was optimizing restricted antibiotic usage. Secondary outcomes included provider compliance, antibiotic days of therapy (DOT), hospital length of stay (LOS), and readmissions within 30 days.

Table 1

Restricted antibiotics

Results

50 patients were included in the study. Restricted antibiotic orders for 18 out of 24 patients in the post-implementation group (75%) were compliant with obtaining pre-approval. Vancomycin, cefepime, and metronidazole were the most common agents ordered. The most common indications were skin and soft tissue infections, musculoskeletal infections, and preemptive sepsis coverage. Patients receiving restricted antibiotics decreased by two (-7.7%) while total restricted antibiotic orders increased by five (16.7%) following ASP implementation. Mean antibiotic DOT increased by 2.02 days (42.7%) and mean hospital LOS increased by 1.8 days (31.0%) in the post-implementation group. There was no difference in 30-day readmissions.

Figure 1

Restricted antibiotics ordered post-implementation of a pediatric antimicrobial stewardship program.

Figure 2

Use of restricted antibiotics pre- and post-implementation of a pediatric antimicrobial stewardship program

Conclusion

The results of this study not only aided in establishing baseline data but also provided a starting point for future efforts concerning the appropriate use of restricted antibiotics. While the findings were inconsistent with those of other institutions, incomplete program compliance and patient complexity in the post-implementation group likely contributed to the increase in DOT and hospital LOS. A longer study duration is needed to assess the true impact of this program.

Disclosures

All Authors: No reported disclosures
1654. Impact of a Daily Web-Based Educational Quiz on Appropriateness of Pediatric Outpatient Antibiotic Prescribing
Authors: Lehrer Brittany J , Banerjee Ritu , Katz Sophie E
Published: November 2023

Background

Nearly ⅓ of outpatient antibiotic prescriptions are unnecessary or inappropriate. QuizTime is a web-based application based on Test-Enhanced Learning Theory that delivers daily case-based questions to a learner’s email or cell phone. We performed a prospective cohort study to evaluate the impact of a QuizTime module on appropriateness of pediatric outpatient antibiotic prescriptions.

Methods

Participants received one question daily for 10 days starting in July 2022. Quiz topics included age-appropriate antibiotic duration for acute otitis media (AOM), empiric antibiotics for uncomplicated urinary tract infections (UTI), and empiric antibiotics and duration for community-acquired pneumonia (CAP) (Table 1). Participants were pediatric prescribers (physician, resident, physician assistant, nurse practitioner) in a primary care, urgent care, retail health, or emergency department setting. Antibiotic prescription data were collected during the “baseline” period (Jul 1, 2021 – Jun 30, 2022) though 3 months after QuizTime participation (Jul 15 – Oct 15 2022) defined as the “post-quiz” period. Pre- and post-intervention data were analyzed in aggregate (not at the provider-level). Significance was determined by calculating a 95% confidence interval (CI) for the difference of proportions. Outcome measures are listed in Table 1.Figure 1.Prisma diagram showing providers and oral antibiotics prescribed in each cohort.

Results

Eighty clinicians participated in QuizTime totaling 13,478 antibiotic prescriptions [AOM 5,613 (41.6%), UTI 668 (5.0%), CAP 225 (1.7%)] compared to 776 non-QuizTime clinicians totaling 43,321 antibiotic prescriptions [AOM 15,258 (35.2 %), UTI 2,528 (5.8%), CAP 849 (2.0%)] (Figure 1). AOM guideline-concordant antibiotic duration was significantly higher among participants than non-participants (Table 2). There were encouraging trends towards improvement in secondary outcomes (Table 3, 4).

Conclusion

Clinicians who participated in a QuizTime module on pediatric outpatient antibiotic prescribing showed improvement in antibiotic appropriateness suggesting web-based microlearning modules are an effective tool for disseminating antibiotic stewardship education. Creation, dissemination, and evaluation of additional QuizTime modules is ongoing.

Disclosures

Ritu Banerjee, MD, Ph.D, bioMerieux: Grant/Research Support|bioMerieux: company is providing partial support for an ongoing trial unrelated to submitted abstract Sophie E. Katz, MD MPH, Dolly Parton Pediatric Infectious Diseases Research Funds: Grant/Research Support|Optum: Advisor/Consultant|Pfizer: Grant/Research Support