bluuebunny/crossref_metadata_2025 huggingface dataset:
1609. Engagement in Care, Awareness, and Interest in Long-Acting Injectable Anti-Retroviral Therapy
Authors: Stout Jacob , Allamong Maxwell , Hung Frances , Link Katherine , Chan Cliburn , Muiruri Charles , Sauceda John , McKellar Mehri
Published: November 2023

Background

Long Acting Injectable (LAI) therapy to treat HIV is now a viable alternative to daily oral medications. The success of early roll-out of LAI to eligible patients requires a better understanding of patients’ awareness and interest in this novel therapy.

Methods

We administered an electronic survey to patients attending an urban HIV clinic in the US South (Duke University). Eligible participants were 18+ years old with a most recent HIV-1 viral load < 200 copies/ml, without any evidence of genotypic resistance to LAI components or chronic hepatitis B. Survey recipients were asked questions on their current treatment, their awareness and interest in LAI, and were asked to rate common benefits and concerns associated with LAI. After probing awareness of LAI, patients were provided further details on LAI for consideration for the rest of the survey. The survey also included the 3-item Brief Index of Engagement in HIV Care, a patient-reported measure of engagement in HIV care that has predicted future retention in care outcomes.

Results

Between January-April 2023, 480 patients were screened; 319 were found to be eligible, and 159 (50%) completed the survey. 73% were male; 44% Black, 7% Latinx; mean age was 49. The majority (119, 76%) were aware of injectable treatments, and 87 (56%) were interested in LAI. Among proposed benefits of injectables, ease of travel without pills, fewer medication interactions, and lack of daily pill-taking were most appealing. Among proposed concerns with injectables, out of pocket cost and insurance coverage of the new medicine were most worrisome. Black patients were more likely to be interested in LAI, and interested patients tended to be younger, single, and more recently diagnosed with HIV. Overall, patients surveyed were highly engaged in care (Mean 4.5/5, SD: 0.5)., but engagement was not predictive of awareness or interest in LAI.

This table summarizes and compares the key patient characteristics between the patients who rated themselves interested or not interested in LAI

Conclusion

As we roll out LAI in real world settings, it will be helpful to characterize which patients are most interested in order to optimize uptake and benefit. Ease of travel without pills, not having to remember daily doses, and fewer medication interactions were the most appealing reasons, while concerns about both insurance coverage and out of pocket cost will need to be addressed.

Disclosures

Mehri McKellar, MD, Gilead Sciences, Inc: Grant/Research Support
1623. Assessing Clinical Evaluation and Patterns of Treatment in Nationally Reported Cases of Congenital Syphilis in Liveborn Infants – United States, 2016–2021
Authors: O’Callaghan Kevin P , Jones Michelle L Johnson , Jackson David A , Torrone Elizabeth
Published: November 2023

Background

Congenital syphilis (CS) rates have increased in the United States since 2013. Management of infants exposed to syphilis during pregnancy entails a detailed clinical evaluation, followed by stratified work-up and treatment.

Methods

During 2016─2021, 9,827 surveillance cases of CS were notified to the National Notifiable Diseases Surveillance System. Using the clinical framework described in the 2015 CDC Sexually Transmitted Diseases Treatment Guidelines, we assigned a clinical scenario (Proven or Highly Probable CS, Possible CS, CS Less Likely, and CS Unlikely) to 8,280 liveborn cases which had sufficient data for case classification (Figure 1). Based on data documented in the case report, we described the elements of evaluation and therapy provided to neonates, assessing whether they met, were in excess of, or were less extensive than recommendations, and stratified these findings by race, ethnicity, and geography.

Results

Of the 8,280 surveillance cases which were assigned a clinical scenario, the majority (80.9%) were classified as Possible CS, of whom 60.7% received an appropriate evaluation, while 68.4% received appropriate treatment. Of those assigned to Proven or Highly Probable CS, 46.0% received an appropriate evaluation, while 82.3% received appropriate treatment.

By U.S. census region, infants born in the Northeast were most likely to receive evaluation (75.7%) and treatment (87.3%) at or above recommendations for their case scenario, while infants born in the South were least likely to receive at or above recommended evaluation (49.5%) and treatment (59.3%). Infants born to a birth parent reporting non-Hispanic Native Hawaiian/Pacific Islander race were most likely to report less than recommended evaluation (36.7%), while infants of a non-Hispanic Black birth parent were most likely to experience less than recommended treatment (32.2%).

Conclusion

This analysis of CS clinical scenarios underscores disparities in evaluation and therapy across geographic, racial, and ethnic lines. Further research is needed to understand factors involved in the evaluation and treatment of infants affected by CS, particularly for those born in the South and to birthing parents reporting minority racial and ethnic backgrounds.

Disclosures

All Authors: No reported disclosures
1645. Predicting Vancomycin Area Under the Curve by Bayesian-Guided Dosing in Pediatric Patients
Authors: Shin Donghyun , Park So Eun , Choi Soo-Han
Published: November 2023

Background

In revised consensus guidelines for therapeutic monitoring of vancomycin, the area under the curve (AUC)-guided monitoring, preferably with Bayesian estimation, is suggested for all pediatric age groups. Recommended AUC target in pediatrics is 400 mg·h/L (potentially up to 600 mg·h/L). However, there is limited pediatric data on validating Bayesian dose-optimizing and predicting vancomycin AUC. We aimed to evaluate the accuracy of the predicted AUC on vancomycin dosing adjustments based on Bayesian estimation.

Methods

We reviewed 25 pediatric patients’ data on vancomycin therapeutic drug monitoring (TDM), including trough concentrations (Ct) and AUC. A Bayesian dose-optimizing software program was used to calculate vancomycin AUC. A second TDM was taken after vancomycin dosing adjustments were performed based on the first TDM. The accuracy was calculated by the ratio of the second AUC to the predicted AUC by Bayesian dose optimization.

Results

The median age of patients was 14.3 years old (interquartile range [IQR], 9.2-16.8). The median vancomycin dosage was 41.7 mg/kg/day (IQR, 33.9-50.0). In the first TDM of vancomycin, the median Ct and AUC were 6.1 ug/mL (IQR, 2.8-11.0; 95% confidence interval [CI], 4.2-9.2) and 320.0 mg·h/L (IQR, 251.5-486.8; 95% CI, 284.0-357.0), respectively. Vancomycin dose increase was required in 68.0% of patients; the median dosage was 50.0 mg/kg/day (IQR, 38.8-60.0). Based on Bayesian-guided dosing adjustments, the median predicted AUC was 420.0 (95% CI, 380.0-447.0). In the second TDM, the median Ct and AUC were 8.7 ug/mL (IQR, 6.2-12.2; 95% CI, 7.5-11.0) and 428.0 mg·h/L (IQR, 369.7-514.0; 95% CI, 384.0-486.0), respectively. The accuracy was 1.033 (95% CI, 0.941-1.307).

Conclusion

The Bayesian AUC-guided dosing strategy may be optimal for individualizing vancomycin therapy in pediatric patients.

Disclosures

All Authors: No reported disclosures
1663. Clostridioides difficile testing following 18706 Pediatric Procedures: Implications for Diagnostic Stewardship
Authors: Negi Ruchita , Deshpande Abhishek , Arakoni Venkatraman , Foster Charles B
Published: November 2023

Background

Clostridioides difficile infection (CDI) poses a risk to surgical patients and antibiotic exposure may contribute to non-infectious diarrhea and unnecessary C diff testing (CDT). Our study evaluates the burden of CDT and CDI in children undergoing procedures with preoperative antibiotic prophylaxis.

Methods

A retrospective cohort study (Jan 2013-Feb 2022) analyzed CDT by Toxin B PCR in children (2-18 years) undergoing sedated procedures with preoperative antibiotic prophylaxis at Cleveland Clinic Children’s. Two step testing with EIA to confirm CDI began in Jun 2018. Perioperative data from an anesthesia database were joined with CPT4 codes and organized by procedure categories used for prophylactic antibiotic selection. CDT and CDI rates by PCR for postoperative days 3-30 were compared based on antibiotic choice (cefazolin as reference) and procedure type (orthopedics as reference) using rate ratios (RR) and mid-p exact test.

Results

A total of 14229 children underwent 18706 procedures. Postoperative CDT, PCR negative and PCR positive rates were 12.2, 10.3 and 1.9/1000 procedures, respectively (Table 1). Of 11 PCR positive tests followed by EIA, 8 were positive (73%). CDT rates were highest for gastrointestinal (GI; 48.4), thoracic (20.8) and neurosurgery (12.8) procedures (Figure 1). CDI rates by PCR were increased for GI procedures (5.9; P < 0.001) and did not differ by antibiotic category. Compared to orthopedic procedures, the RR for negative CDT was highest for GI procedures 71.46 (28.73-229.4; P < 0.001). For antibiotics (Figure 2), the lowest CDT rate was for cefazolin (7.1). Compared to cefazolin, the negative CDT RR was 16.23 (10.97-23.69; P < 0.001) for metronidazole, 10.06 (7.23-13.95; P < 0.001) for broad spectrum antibiotics and 8.39 (5.60-12.36; P < 0.001) for vancomycin.

C difficile Negative and Positive Testing Rates in the 30-Days Following Pediatric Procedures Requiring Preoperative Antibiotic Prophylaxis, Stratified According to Prophylactic Antibiotic Category and Procedure Category Used to Select Prophylactic Antibiotic

Conclusion

The study demonstrates that CDT rates by PCR vary by procedure type and antibiotic prophylaxis regimen. Both CDI and CDT rates were higher for GI procedures. Negative CDT rates were especially high for GI procedures and for antibiotic prophylaxis with non-cefazolin containing regimens. High postoperative rates of negative CDT suggest that non-infectious diarrhea contributes to testing. These studies are relevant to diagnostic stewardship efforts aimed at preventing unnecessary CDT.

Disclosures

Abhishek Deshpande, MD; PhD, Merck: Advisor/Consultant|Seres Therapeutics: Grant/Research Support Charles B. Foster, MD, 3M Co: Stocks/Bonds|Novavax: Stocks/Bonds|Scynexis: Stocks/Bonds|Veru Inc: Stocks/Bonds|Vir Biotechnology: Stocks/Bonds
1678. Non-Invasive and invasive Pediatric Group A Streptococcus Infections (iGAS) Admissions During 2021 and 2022 at a Tertiary Health Care Center: Resurgence and Concomitant Viral Infections
Authors: Fields Susan , Butler Caroline , Chappell Sarah , Neshangi Srilatha , Camelo Ingrid
Published: November 2023

Background

A resurgence of invasive Group A Streptococcus (iGAS) infection in children was observed in Colorado and Minnesota by the Centers For Disease Control and Prevention (CDC) during the fall of 2022. Cases were accompanied by hospitalizations for respiratory syncytial virus (RSV) and influenza. We describe hospital admissions with iGAS and non iGAS infections at a tertiary health care center in Augusta, GA during 2021 and 2022; the only children’s Hospital with 150 licensed beds and a population of 201.196 as of 2021.

Methods

We used the iGAS definition by the CDC as a Group A Streptococcus (GAS) isolated by culture in specimens obtained from a sterile body site, or GAS isolated from wound culture and necrotizing fasciitis or streptococcal toxic shock syndrome. We conducted a retrospective chart review of iGAS and non iGAS cases admitted to the Children’s Hospital of Georgia during January to December 2021 and January to December 2022. We collected demographics, site of infection, concomitant viral infections diagnosed by nasopharyngeal (NP) PCR, intensive care unit (ICU) admission and mortality.

Results

During 2021, only 1 patient was admitted with non iGAS, a 7-year-old with a wound infection. In 2022, 15 patients were diagnosed with GAS infection, 7 of them had iGAS and 8 had noninvasive disease. We included positive peritoneal and pleural fluid, joint/bone aspirates, bronchoalveolar lavage samples, and blood cultures for iGAS. The age range for iGAS was 6-17 years and for noninvasive, 16 mo to 11 years. In 2022, 25% of noninvasive cases had concomitant influenza compared to 43% of iGAS cases. Only one patient with non iGAS tested positive for RSV. 2 patients had rhinovirus, one had adenovirus. One patient with iGAS was positive for metapneumovirus (HMPV). 57% of iGAS cases were admitted to the ICU (n=4). 50% of noninvasive cases (n=4) were admitted to the ICU. One iGAs case died. All noninvasive cases survived.

Conclusion

There was increase in iGAS and noninvasive GAS infections during 2022 compared to 2021 in our institution. iGAS was more common in older children. Of iGAS cases, the only coexisting viruses were influenza and HMPV. Most cases were seen during Fall of 2022. The cause of reappearance of iGAS and non iGAS is still unknown but believed to be related to end of mask mandates for COVID 19 infections.

Disclosures

All Authors: No reported disclosures
1680. Characterization of Ethanol Lock Use and Line Infections in Pediatric Patients with Intestinal Failure Requiring Central Venous Access
Authors: Davidge Karen , Mroczka Elizabeth , Ivy Chelsey , Nagel Jerod
Published: November 2023

Background

Pediatric patients with intestinal failure often require central venous line access for administration of parenteral nutrition and/or fluids, which leads to increased risk for central line associated-bloodstream infections (CLABSI). Ethanol lock therapy (ELT) has been used to reduce the risk of CLABSI in this patient population, but recent significant increases in the price of ethanol have prompted healthcare systems to explore cost-saving measures such as decreasing ELT frequency from daily to thrice weekly (TIW) or using antibiotic lock therapy as an alternative to ELT. The objective of this study was to compare the incidence and microbiology of CLABSI in pediatric patients with intestinal failure who received different lock therapies.

Methods

This was a single-center, retrospective, descriptive study that included pediatric patients who were followed by the Michigan Medicine Children’s Intestinal Rehabilitation Program between July 1, 2020 and June 30, 2022. Data were collected via the electronic health record. Incidence of CLABSI and microbiology were compared based on the type of lock therapy patients received (daily ELT, TIW ELT, or no ELT).

Results

A total of 46 patients were analyzed in this study, including 13 on daily ELT, 23 on TIW ELT, and 10 on no ELT. During the study period, 69% (9/13) of patients on daily ELT, 35% (8/23) of patients on TIW ELT, and 60% (6/10) of patients on no ELT had at least one CLABSI (for comparison between daily and TIW ELT, p = 0.0819). Of 75 episodes of CLABSI identified during the study period, the most commonly isolated pathogens were Staphylococcus epidermidis (n = 33), S. aureus (n = 19), S. hominis (n = 17), and Escherichia coli (n = 8). Almost half (44%, 33/75) of CLABSI reported were polymicrobial (see Table 1 for comparison of microbiology by type of lock therapy).Table 1:Number of monomicrobial vs. polymicrobial CLABSI by Gram stain results and type of lock therapy.

Conclusion

There was no statistically significant difference in the incidence of CLABSI between pediatric patients with intestinal failure who received TIW ELT and those who received either daily ELT or no ELT. TIW ELT appears to be an effective and cost-efficient option compared to daily ELT in this patient population.

Disclosures

All Authors: No reported disclosures
1725. Differences in serotype 3 antibody response and antibody functionality compared to serotype 19A following 13-valent pneumococcal conjugate immunization in children
Authors: Fuji Naoko , Pham Minh , Kaur Ravinder , Pichichero Michael
Published: November 2023

Background

Background. 13-valent pneumococcal conjugate vaccine (PCV13) includes serotype 3 and 19A. However, prevention of infections with PCV13 may be less effective against serotype 3 than 19A. In young children, determine differences in IgG antibody levels, functionality of antibody by OPA and antibody avidity for serotype 3 compared to 19A following PCV13 immunization; determine IgG antibody levels following natural immunization for serotype 3 and 19A; reassess effectiveness of PCV13 against serotype 3 and 19A in prevention of acute otitis media (AOM) and colonization.

Methods

Samples were secured during a prospective longitudinal study conducted in Rochester NY of children age 6-36 months old. Pneumococcal detection was determined by culture. 713 serum samples were tested for antibody levels by ELISA, 68 serum for functional antibody by OPA, and 47 serum for antibody avidity by thiocyanate bond disruption. Age effects on antibody levels was modeled by generalized estimating equations. PCV13 effectiveness was assessed compared to pre-PCV13.

Results

The proportion children who did not reach protective threshold against IPD (< 0.35 µg/ml) after PCV13 immunization was higher for serotype 3 antibody compared to 19A. PCV13-induced antibody levels to serotype 3 were1.4 to 3.4 fold lower than 19A. OPA titers were not significantly different for serotype 3 compared to 19A, but antibody avidity at child age 6 and 15 months was significantly lower. Serotype 3 natural- immunized children showed a positive trend of increase in antibody level as children got older. In contrast, PCV13-immunized children showed a negative trend of antibody levels with age. For serotype 19A, both natural immunization and PCV13 immunization showed a positive trend in antibody levels over age. PCV13 effectiveness was not identified in preventing AOM or colonization for serotype 3 but effectiveness of 19A was re-confirmed.

Conclusion

Conclusions: PCV13 elicits lower antibody levels and lower avidity antibody to serotype 3 than 19A. PCV13 does not elicit antibody levels that increase over age despite a booster dose for serotype 3, as occurs for serotype 19A. Post PCV13-induced antibody levels for serotype 3 may be insufficient to prevent AOM and colonization in young children.

Disclosures

All Authors: No reported disclosures
1729. Literature Review to Identify Evidence of Secondary Transmission of ROTATEQ® (RV5) Vaccine Strains to Unvaccinated Subjects
Authors: Li Yuanqiu , Sun Xiaojin , Fu Yaqun , You Xuedan , Hartwig Susanne
Published: November 2023

Background

Rotavirus (RV) is the leading cause of severe diarrhea in infants and young children. RV vaccination is recommended by WHO since 2009 for all children worldwide, especially in countries with a high number of diarrhea-associated deaths. Live attenuated vaccines can lead to horizontal transmission with the risk of vaccine-derived disease in contacts. Transmission of RV5 strains leading to clinical disease was not well evaluated in the pivotal clinical trials and only few case-reports have been described in the literature.

Methods

We performed a systematic literature review to investigate secondary transmission of RV5 vaccine strains to unvaccinated subjects globally. We searched Embase, Medline for English papers, CNKI, Wan Fang for Chinese papers and other resources (i.e., conference papers with full text, preprint platform including bioRxiv and medRxiv) from January 2005 to June 2021. Eligibility criteria for inclusion were original articles bases on non-interventional studies (case-control studies, cohort studies, cross-sectional studies) using RV5 vaccine strain transmission as outcomes. Other study or publication types were excluded such as pre-clinical studies, interventional studies and case reports. A Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) was used and study quality was assessed using the Newcastle Ottawa Scale (NOS) for cohort studies and the JBI checklist for cross-sectional studies to assess risk of bias.

Results

The search generated 2,089 articles in total. Seven articles met all inclusion criteria, including six cohort studies and one cross-sectional study. All studies underwent quality assessment and complied with the quality criteria of NOS or JBI checklist respectively. Overall, none of the seven studies identified RV5 vaccine-type transmission to an unvaccinated population, in either hospitals or nurseries under a close contact environment. One study reported that 1% of unvaccinated infants had gastrointestinal symptoms but all symptoms were attributed to other clinical conditions.

Conclusion

We found no evidence of horizontal transmission of RV5 vaccine virus strains to unvaccinated infants despite the limited amount and descriptive nature of the identified studies.

Disclosures

All Authors: No reported disclosures
1743. Health Care Resource Utilisation (HCRU) Due to Respiratory Syncytial Virus (RSV) Before the Age of Two in England
Authors: Fonseca Maria João , Bangert Mathieu , Kramer Rolf , Cirneanu Lorena , Hudson Richard
Published: November 2023

Background

RSV is responsible for 33 million lower respiratory tract infections (LRTI) worldwide. The highest burden occurs in infants < 1 year of age during RSV season, which is from October to February in England. Due to lack of routine laboratory testing, its true disease burden is unknown. This study aimed to estimate the respiratory related primary and secondary care healthcare resource utilisation (HCRU) of RSV admissions before the age two in England.

Methods

This retrospective cohort study used Clinical Practice Research Datalink (CPRD)-Hospital Episode Statistics (HES) linked data to establish a birth cohort of all infants born between 01/03/2015 and 28/02/2017 (n=449,591). Case cohorts included infants under two with a hospital admission of: 1) confirmed RSV (n=4,813), 2) bronchiolitis (n=22,913), 3) any RTI (n=56,871). Each case cohort was compared with all birth cohort infants without the corresponding admission (comparative cohorts). Respiratory related HCRU (primary care, outpatient, accident and emergency [A&E], and inpatient admissions) were estimated in the month prior to and up to 24 months following the first admission in each cohort.

Results

The RSV-coded cohort had the highest HCRU overall, mean (SD) of 5.1 (4.8) admissions vs. 1.5 (2.4) in its comparative cohort (71% difference). This difference was largely due to A&E and inpatient admissions. Comparable results were found for bronchiolitis-coded and RTI-coded cohorts. The highest rates of inpatient admissions were observed for the RSV-coded case cohort, and these occurred during the calendar months of November and December. Inpatient admissions were largely among infants up to 12 months of age and included infants that were born both before and during the season (Figure 1).

Conclusion

Infants with an RSV admission had higher HCRU than infants without. Most hospitalisations occurred in November and December when services are at their most stretched. During the first year of life, the HCRU rates observed for infants born before and in the season were equally very high, emphasizing the need for preventative strategies to all infants entering their first RSV season. Funding: This research was funded by collaborative agreement with Sanofi / AstraZeneca and is part of the RODEO research program for RSV disease.

Disclosures

Maria João Fonseca, n/a, Sanofi: Advisor/Consultant Mathieu Bangert, PhD, Sanofi: Staff member Rolf Kramer, n/a, Sanofi: Stocks/Bonds Richard Hudson, n/a, Sanofi: I am an employee of Sanofi|Sanofi: Stocks/Bonds
1780. COVID-19 Vaccine Accessibility and Uptake among U.S. Children Aged 6 Months-4 Years and 5 Years-11 Years by Domains of Social Vulnerability
Authors: Khazanchi Rohan , Rader Benjamin , Cantor Jonathan , Bravata Dena M , McManus Kathleen A , Whaley Christopher , Weintraub Rebecca , Brownstein John
Published: November 2023

Background

The COVID-19 pandemic, and pandemic-related interventions, have had markedly disparate effects on marginalized populations. We examined whether the inequitable distribution of other COVID-19 resources was similarly reflected within the pediatric vaccination rollout.

Methods

We analyzed from a comprehensive national database of U.S. pediatric vaccination distribution sites and administered doses (VaccineFinder) as of 7/29/2022. We ascertained accessibility by geocoding sites, measuring one-way travel times from every Census tract population center to the nearest site, and weighting tracts by population demographics (rurality, age, race, ethnicity) to obtain nationwide estimates. We used population-weighted quasipoisson regressions adjusted for state fixed effects to compare vaccination uptake between the most and least socially vulnerable quartiles of counties by Social Vulnerability Index (SVI) domains (socioeconomic status, SES; household composition & disability, HCD; minority status & language, MSL; housing type & transportation, HTT).

Results

We identified 15,233,956 total vaccine doses administered across 27,526 sites. Rural, non-Hispanic, White, and Native populations had longer one-way travel times to the nearest pediatric vaccination site than urban, Hispanic, Black, and Asian populations. Greater social vulnerability by overall SVI, SES, and HCD was associated with decreased vaccine uptake among children in the 6mo-4y (Overall: IRR 0.70 [95%CI 0.60-0.81], SES: 0.66 [0.58-0.75], HCD: 0.38 [0.33-0.44]) and 5y-11y (Overall: 0.85 [0.77-0.95], SES: 0.71 [0.65-0.78], HCD: 0.67 [0.61-0.74]) groups, whereas greater social vulnerability by MSL was associated with increased uptake in both age groups (6mo-4y: 5.16 [3.59-7.42], 5y-11y: 1.73 [1.44-2.08]).

Figure 1. Geospatial Visualization of One-Way Travel Time to the Nearest COVID-19 Vaccination Site by Age Figure 2. One-Way Travel Time to the Nearest 6mo-4y COVID-19 Vaccination Site by Race, Ethnicity, Rurality Figure 3. One-Way Travel Time to the Nearest 5y-11y COVID-19 Vaccination Site by Race, Ethnicity, Rurality

Conclusion

We identified meaningful spatial patterns in the accessibility and uptake of pediatric COVID-19 vaccinations, including decreased vaccine uptake in areas of high SES and HCD vulnerability and greater uptake in areas of high MSL vulnerability. Our modeling and surveillance approaches are generalizable and can be applied to other emerging pathogen response and scarce resource allocation efforts.

Disclosures

Dena M. Bravata, MD, MS, Castlight Health: Advisor/Consultant Kathleen A. McManus, MD, MSCR, Gilead Sciences, Inc.: Stocks/Bonds
1818. A Network Meta-Analysis of Antibiotic Efficacy for the Treatment of Skin and Soft Tissue Infections
Authors: Go-Wheeler Marianne , Mann Sarah C , Hean Sindalisa , Schwartz Matthew H , Pham Ann , Judge Stephen , Kang Amy Y , Lee Pamela , Gil Raul Macias , Launer Bryn M , Tao Li , Miller Elliot I , Flores Evelyn A , Nguyen Megan H , Yeh Maddie , Speciale Christiana , Miller Loren G
Published: November 2023

Background

Skin and soft tissue infections (SSTIs) are very common bacterial infections. Numerous clinical trials have compared antibiotics for SSTI treatment. However, trials typically have non-inferiority designs that give little insight as to which antibiotic classes have superior efficacy.

Methods

We performed a systematic literature review and a network meta-analysis of published SSTI treatment trials. Using standardized key words, we searched PubMed and Embase for SSTI clinical trials published from 1/1/66 to 5/31/22. We excluded trials on diabetic foot infections, non-generalizable populations (e.g., burn associated), and studies with outcomes not involving clinical resolution or cure. Abstracts with relevant clinical trial data were pulled and, if inclusion criteria met, had manuscript data abstracted. Two reviewers independently performed abstract and manuscripts reviews and data abstraction. For the network meta-analyses, the comparator antibiotic class was glycopeptides. Two analyses were performed using intention to treat (ITT) and clinically evaluable (CE) populations. Clinical trial quality was measured using the PEDro score.

Results

We reviewed 5,469 abstracts, of which 260 were pulled for data abstraction and 93 contained analyzable trial data (Fig. 1). Clinical trial quality varied widely (PEDro score range 2-10, median 8). We identified 26 analyzable antibiotic classes or combinations for comparison. In the ITT model, cure rate for oxazolidinones (OR 1.28 [95% CI 1.10-1.49]), flucloxacillin plus clindamycin (OR 1.61 [95% CI 1.03-2.53]), lipopeptides (OR 1.66 [95% CI 1.04-2.66]), and tetracyclines OR 1.69 [95% CI 1.24-2.30]), significantly differed from glycopeptides. (Fig. 2) In the CE model, cure rate for oxazolidinones (OR 1.29 [95% CI 1.01-1.64]) and tetracyclines (OR 2.05 [95% CI 1.37-3.06]) significantly differed.

Conclusion

We found that most (22/26) antibiotic classes or combinations used for SSTI treatment had similar efficacy to glycopeptides. However, oxazolidinones, lipopeptides, flucloxacillin plus clindamycin, and tetracyclines may have superior efficacy compared to glycopeptides. Treatment guidelines may wish to favor these latter classes for patients at high risk of treatment failure.

Disclosures

Amy Y. Kang, Pharm.D., BCIDP, Paratek: Grant/Research Support Elliot I. Miller, BS, Epic Systems, Verona, WI: Employee Loren G. Miller, MD MPH, ContraFect: Grant/Research Support|GSK: Grant/Research Support|Medline: Grant/Research Support|Merck: Grant/Research Support|Paratek: Grant/Research Support
1829. The Impact of Social Determinants of Health on Treatment Route, Duration, and Outcomes in Bone and Joint Infections
Authors: Cummins Heather , Gallagher Chanah , Gray Julie , Benefield Russell J , Certain Laura
Published: November 2023

Background

The Oral versus Intravenous Antibiotics for Bone and Joint Infection (OVIVA) trial concluded that oral antibiotic therapy was noninferior to intravenous antibiotic therapy for complex orthopedic infections. Similar studies have confirmed the OVIVA trials findings. However, there is limited information regarding the impact of Social Determinants of Health (SDOH) on decisions regarding IV vs. PO treatment and treatment outcomes of bone and joint infections. This study aimed to determine how SDOH affect IV vs. PO treatment choices and overall treatment outcomes for patients with bone and joint infections.

Methods

In this single-center cohort, patients discharged between 4/1/2018 and 4/1/2022 were examined. Inclusion criteria were patients who had bone and joint infections, inpatient Infectious Disease (ID) consult, discharged on IV vancomycin, age >18 years, and scheduled follow up in the University of Utah Infectious Disease Clinic. SDOH assessed included primary language, race/ethnicity, insurance, history of intravenous drug use (IVDU), and history of homelessness. The primary outcome was the number of patients switched from IV to PO antibiotics two weeks after discharge. Secondary outcomes included total duration of antibiotics, duration of follow up with ID, and rate of treatment failure.

Results

Two hundred seventy-seven patients met inclusion criteria for the cohort. There was no difference with respect to history of homelessness, primary language, history of IVDU, race, ethnicity, or insurance status in patients who were switched to PO antibiotics within two weeks of discharge compared to patients maintained on IV antibiotics. With respect to secondary outcomes, individuals on Medicaid were more likely to experience treatment failure (Table 1B).

Conclusion

For patients with bone and joint infections, SDOH were not associated with a switch from IV to PO antibiotics. However, patients on Medicaid experienced higher rates of treatment failure despite no difference in antibiotic route. The examined SDOH and transition to PO regimens were infrequently observed among study participants which created difficulty with drawing further conclusions. Further examination of these SDOH is important to understand their impact on treatment failure and improve patient care.

Disclosures

Russell J. Benefield, PharmD, BCPS-AQ ID, Paratek Pharmaceuticals: Grant/Research Support
1853. Examining the Role of Race-Ethnicity and Neighborhood Socioeconomic Disadvantage in Influenza Vaccine Uptake
Authors: Sarode Anuja , Speyer Caitlin , Tisch Daniel J , Saade Elie , Salata Robert
Published: November 2023

Background

Negative influenza-associated outcomes disproportionately impact non-White individuals. Targeted influenza vaccine coverage could improve outcomes in minority groups. This study examined the role of race-ethnicity and resource inequity in vaccine coverage.

Methods

We analyzed data from all outpatient visits at University Hospitals CMC from October 01, 2022 to February 28, 2023. Race, ethnicity, age, sex, income, home address, ICD diagnosis, and influenza immunization records were collected. Patients who received an influenza vaccine between July 01, 2022 and February 28, 2023 were considered immunized. A 9-digit patient zip code was used to obtain state Area Depravity Index (ADI) data provided by University of Wisconsin School of Medicine and Public Health. The state ADI ranges from 1 to 10, with group 1 being the least disadvantaged and 10 being the most disadvantaged. We used logistic regression analysis to estimate the odds for being vaccinated predicted by race-ethnicity, state ADI, age, and sex.

Results

Out of 301,572 hospitalizations, 59.0% were women, 81.2% were White non-Hispanic, 16.0% were Black non-Hispanic, and 2.7% were Hispanic. Black non-Hispanics were most disadvantaged with a mean State ADI of 7.54, followed by Hispanics at 5.64. White non-Hispanics were least disadvantaged with a mean State ADI of 3.99 (p< 0.001)(Table 1). Black non-Hispanics were disproportionately represented in the most disadvantaged areas (27.93%). Black non-Hispanics were 38% less likely to be vaccinated than White non-Hispanics. After ADI, sex, and age adjustment, Black non-Hispanics were 11% less likely to be vaccinated (OR: 0.89; 95% CI: 0.868 - 0.912). With each point increase in State ADI, vaccination rate decreased by 7% (OR: 0.93; 95% CI: 0.928 – 0.933)(Table 3). Regression analysis suggested significant interaction between race-ethnicity and State ADI.

Influenza Vaccination by individual characteristics within overall population and race-ethnicity

Influenza vaccination by race-ethnicity adjusting for State ADI, age, and sex

Influenza vaccination by race-ethnicity adjusting for State ADI and sex, and stratified by age groups

Conclusion

This cross-sectional study found racial and ethnic disparities in rates of influenza vaccination. The effect of race-ethnicity on vaccination rate is dependent on ADI. These data identified subgroups on which to focus future influenza prevention efforts. The generalization of the study is limited and similar analysis from other areas and vaccines would be beneficial.

Disclosures

Elie Saade, MD, MPH, FIDSA, Envision Pharma: Speaker, Presenter|Johnson and Johnson: Speaker, Travel, Lodging|Protein Sciences Corp: Grant/Research Support|Sanofi Pasteur: Speaker, Travel and Lodging
1861. Prevalence of COVID-19 within Predominantly Black Church Congregations in Ontario, Canada
Authors: Wisener Nicole , Litosh Alice , Byrne Walter , Hwang Matthew , Thompson Kimberly , Allen Upton D
Published: November 2023

Background

Seroprevalence data provide useful information on COVID-19 burden among various communities by detecting infection in both symptomatic and asymptomatic persons. One challenge is the extent to which potential participants agree to blood testing. To address this, we conducted a community-based survey to assess infection rates within church congregations to understand COVID-19 prevalence in a closed group setting in contrast to a conventional open community setting.

Methods

A cross-sectional survey was conducted within church congregations consisting of mainly Black members from 09/2022 to 05/2023 in Ontario, Canada. Participants completed the survey in person or online. Demographic data and COVID-19-related information, such as polymerase chain reaction (PCR) or rapid antigen positivity and vaccination status, were collected. Survey data were compared with seroprevalence data collected in a related study.

Results

The survey was completed by 434 persons from 5 different congregations. Male to female ratio 1:2.6. Most participants, 319 (73.5%) completed the survey on paper, in person. The remaining surveys were completed online. Among persons who provided information on age, 50 (12%) survey respondents were 18-30 years of age, 90 (21%) were 31-45, 163 (38%) were 46-60, and 121 (29%) were above 60 years of age. Across all congregations, 46.1% (200/434; 95% CI 41.3-50.9%) reported that they thought they had COVID-19, compared with 39.4% (171/434; 95% CI 34.7-44.1%) who reported testing positive for COVID-19. Among all participants, 9% (40/434) did not receive the COVID-19 vaccine while 88.7% (385/434) completed their primary vaccine series.

Seroprevalence data collected by our team revealed a seropositivity rate of up to 80% for the area where most participants reside or work. Among a subset of persons providing both seroprevalence and survey data, there was concordance in approximately 62% (8/13) of seropositive cases.

Conclusion

The data suggest infection rates reported by a relatively highly vaccinated group of predominantly Black congregants were below that of the general community. Further analyses will examine reasons for these findings.

Disclosures

All Authors: No reported disclosures
1889. The Epidemiology of Nontuberculosis Mycobacteria in a Single Urban Center
Authors: Alsoubani Majd , Park Heidi , Vindenes Tine
Published: November 2023

Background

Non tuberculosis mycobacteria (NTM) are ubiquitous in the environment. The prevalence of NTM has increased worldwide, which is thought to be partly related to increased diagnostic testing but also possible aging populations, increased comorbid conditions and immunosuppression. NTM are considered rapidly emerging infections and often hard to treat. We aim to explore the true burden of NTM at Tufts Medical Center, a tertiary hospital serving a diverse patient population including a large immigrant Asian population

Methods

This was a retrospective case review study done at Tufts Medical Center, a tertiary academic hospital in Boston, MA. We identified adult patients with an ICD-10 diagnosis of NTM between January 2012 and March 2022. Clinical and microbiologic data was collected from the medical record. Patients without microbiology data in our institution were excluded. Chi-square and Fisher’s exact tests were used for categorical variables, student T-test was used for age.

Results

Out of 342 cases with an ICD-10 diagnosis of NTM, 197 patients met our inclusion criteria. In our sample, females represented 51.5% of cases. The majority of cases were white (48.2%) followed by Asian (42.6%). A third of patients with pulmonary NTM had a diagnosis of COPD and only 20% had documented past or current smoking history (Table 1). White patients were more likely to have extra pulmonary NTM compared to Asian patients (24 vs 5, p < 0.001). The most common site of NTM second to lung was skin and soft tissue (n=22, 10.9%). The most common NTM isolated from pulmonary site was Mycobacterium avium (n=85, 51.5%) while rapid growers [Mycobacterium chelonae (n=8, 25%), M.fortuitum (n=7,21.7%), and M. abscessus (n=7, 21.9%)] were the most common NTM isolated in extra pulmonary sites (Table 2).

Conclusion

The epidemiological review of NTM at our urban institution has improved the understanding of the population we serve. Our data show high percentage of Asians with pulmonary NTM cultures and suggest higher predominance of extrapulmonary NTM in Caucasians compared to Asians. The majority of the extrapulmonary NTM were rapid growers. Larger epidemiologic studies and surveillance data are needed to better understand NTM in various environments and hosts.

Disclosures

All Authors: No reported disclosures
1894. Delay in TB care before and during the COVID-19 pandemic, Dushanbe, Tajikistan, 2022
Authors: Sharifov Rajabali , Nabirova Dilyara , Tilloeva Zulfiya Haybullo , Zikriyarova Sanam , Yusufi Salomudin , Jafarov Navruz , Horth Roberta
Published: November 2023

Background

Delays in TB treatment prolong the period of infectivity and are associated with drug resistance. Tajikistan has a high and increasing burden of multidrug-resistant tuberculosis (incidence of 28/100,000 in 2021). Many new cases present with severe disease, indicating delayed care. The COVID-19 pandemic further threatened to undo progress.

Methods

We conducted a retrospective cohort study of people >15 years old newly diagnosed with pulmonary TB in Dushanbe in 2019-2021. We conducted face-to-face interviews using structured questionnaires and abstracted data from medical records. We defined patient-delay as >14 days between TB symptom onset and initial visit, and provider-delay as >3 days from initial visit to treatment initiation. We ran multivariable Poisson regressions to estimate variables associated with presentation-delay and provider-delay.

Results

From 2019-21, 472 people were newly diagnosed with pulmonary TB. Of these, 82% had delayed treatment, 49% were male, 61% had lung tissue decay, 11% had diabetes, and 4% had HIV. Additionally, 42% had been diagnosed in 2019. The proportion with patient-delay was similar before and during the pandemic (83% vs. 82%, respectively, p=0.8). However, the proportion with provider-delay was higher before than during the pandemic (44% vs. 34%, p=0.02). There was no statistical difference in median days of patient-delay before (60 days; interquartile range [IQR]: 15–541) and after (60 days; IQR: 15–360, p=0.6) the pandemic, nor in median days of provider-delay before (7 days; IQR: 4–336) and after (7 days; IQR: 4–225, p=0.6) the pandemic. In multivariable analysis, the COVID-19 pandemic was not associated patient-delay (adjusted risk ratio and 95% confidence interval=1.00; 0.96-1.04). Patient-delay was significantly higher in people who ignored disease symptoms (1.41; 1.20-1.65) and thought services were expensive (1.10; 1.01-1.20) even though they are free of charge (Table 1).

Conclusion

Contrary to expected, presentation-delay for TB diagnosis did not differ before and during the COVID-19 pandemic, and provider-delay was lower. Increased vigilance of respiratory diseases and differential diagnosis for SARS-CoV-2 may have resulted in timelier TB diagnosis. However, interventions to further reduce delays are still needed.

Disclosures

All Authors: No reported disclosures
1899. Core Outcome Domains for Mycobacterium avium complex Pulmonary Disease Clinical Trials: Mycobacterium avium complex Core Outcomes Research (MACCOR)
Authors: Varley Cara D , Stadnik Ryan , Bingham Clifton , Quittner Alexandra L , Lewinsohn David , Winthrop Kevin L
Published: November 2023

Background

Mycobacterium avium complex pulmonary disease (MAC-PD) is a chronic, inflammatory disease with systemic manifestations affecting multiple aspects of patients’ lives. It can require lifelong management, as recurrence is common, however current microbiologic outcomes are often difficult to obtain and insufficient to reflect the impact on patients. We aim to identify the core outcome domains essential to evaluate in future clinical research studies of outcomes in MAC-PD, using an international consensus process, and we describe the Round 1 preliminary results.

Methods

We invited relevant stakeholders in MAC-PD research including patients, caregivers/family members, clinicians, researchers, nonprofit and patient education organizations, and federal research funding organizations to participate in the Delphi consensus process. We used respondent driven sampling to expand our cohort. Participants were asked to rate preliminary domain importance, without regard to availability, feasibility, or validity of measurement instruments, using the Grading of Recommendations Assessment, Development and Evaluation scale (score 1-9). We administered surveys via email through DelphiManager software. We used SAS version 9.4 to describe our participants and the Round 1 core outcome domain scores.

Results

We had a total of 48 participants, including 30 (62.5%) clinicians, 10 (20.8%) researchers, 6 (12.5%) patients, and 2 (4.2%) from organizations that fund MAC-PD research. A majority were women (27, 56.3%), ages 60-69 (16, 33.3%) who identified as White (39, 81.3%) and were from North America (45, 93.8%). Most had 10 years or more experience (33, 68.8%) in their MAC-PD stakeholder role. Symptoms, Microbiology, Treatment Side effects, Chest imaging, Physical function, Treatment burden, and Vitality/Energy domains were rated as Critical (score >7) by more than 70% and had fewer than 15% identifying the domain as Not Important (score <3).

Conclusion

We report the initial evaluation of core outcome domains for MAC-PD through an international consensus process. Identification and dissemination of these domains will help guide research priorities on future outcome measures.

Disclosures

Alexandra L. Quittner, PhD, AN2: Advisor/Consultant|Insmed Pharmaceutical Corp: Advisor/Consultant Kevin L. Winthrop, MD, MPH, AN2: Advisor/Consultant|AN2: Grant/Research Support|Insmed: Advisor/Consultant|Insmed: Grant/Research Support|Insmed: This study was funded by Insmed Inc.|Paratek: Advisor/Consultant|Paratek: Grant/Research Support|Red Hill Biopharma: Advisor/Consultant|Red Hill Biopharma: Board Member|Red Hill Biopharma: Grant/Research Support|Renovion: Advisor/Consultant|Renovion: Grant/Research Support|Spero: Advisor/Consultant|Spero: Grant/Research Support
2110. Enhancing Antibiotic Efficacy Against Enterococcal faecium with Bacteriophage and Antimicrobial Peptides
Authors: Bleick Callan , Stamper Kyle , Mohib Sumaiya , Avery Shaylyn , Biswas Biswagit , Arias Cesar A , Rybak Michael J
Published: November 2023

Background

The urgency to find new alternatives has increased as multidrug-resistant organisms enhance their defense mechanisms. In recent years, there has been a renewed interest in bacteriophages as potential alternatives or adjuncts to antibiotic therapy. However, there is limited information on the impact of bacteriophages with the innate immune system. Cathelicidin LL-37, a cationic peptide with antimicrobial properties, functions in coordination with the immune system to eradicate pathogens. We aim to evaluate how the survival of daptomycin (DAP) and ampicillin (AMP) resistant or non-susceptible Enterococcus faecium isolates are impacted by the interaction between bacteriophage, LL-37, and the addition of DAP/AMP.

Methods

Two E. faecium clinical isolates were utilized: R497 and HOU503. Bacteriophages provided by the Naval Medical Research Command, NV- 503-01 and NV-497 were quantified and propagated to approximately 108 PFU/mL. LL-37 was prepared at a final concentration of 640μM and diluted in RPMI intentionally to a suboptimal concentration of 0.5μM to adjust for a 70-80% survival rate. This was done to detect a synergistic interaction more easily with the addition of phage. Samples were incubated at 37 °C and plated in triplicate on brain heart infusion agar at 2h. After 24h of incubation, colonies were counted for and analyzed. Data was expressed as a mean percent survival with standard deviation. ANOVA with Tukey's HSD post-hoc test was used to determine the variations between each combination used.

Results

The targeted bacterial survival rate against E. faecium isolates was attained by LL-37 at a concentration of 0.5μM. However, when R497 and HOU503 was combined with LL-37, bacteriophage, and DAP/AMP the percentage of bacterial survival was significantly (P< 0.05) lower than that of the growth control, LL-37, AMP/DAP, and bacteriophage alone.

Conclusion

By conducting bacterial survival assays, we observed a notable enhancement in the elimination of multi-drug resistant E. faecium when LL-37, bacteriophage, and DAP/AMP were added. Examining this interaction over longer periods, both with and without varying antimicrobials, will yield more understanding regarding the potential involvement of bacteriophage in the innate immune system's response to fighting infections.

Disclosures

Michael J. Rybak, PharmD, PhD, MPH, Abbvie, Merck, Paratek, Shionogi, Entasis, La Jolla, T2 Biosystems: Advisor/Consultant