bluuebunny/crossref_metadata_2025_split huggingface dataset:
65. In Vivo Efficacy of Human Simulated Minocycline (MIN) against Stenotrophomonas maltophilia (STM)
Authors: Fratoni Andrew J , Nicolau David P , Kuti Joseph L 
Published: December 2021

Abstract

Background
The current susceptibility breakpoint for MIN against STM is 4mg/L, yielding &gt;99% of isolates susceptible. Unfortunately, there are limited pre-clinical and clinical data to support this breakpoint for STM. The purpose of this study was to evaluate the efficacy of a MIN human simulated regimen (HSR) against STM across a wide range of MICs in the murine neutropenic thigh model.

Methods
Clinical STM with modal MIN MICS of 0.25-8mg/L were included. Confirmatory pharmacokinetic (PK) studies were performed in infected neutropenic mice to develop a MIN HSR providing an area under the curve (AUC) and maximum concentration (Cmax) exposure similar to MIN 100mg intravenous (IV) q12h at steady-state based on PK parameters from critically ill adult patients. The murine neutropenic thigh infection model was utilized to examine the antibacterial effects of the confirmed MIN HSR against 17 STM. Both thighs of neutropenic ICR mice were inoculated with bacterial suspensions of 107 colony forming units (CFU)/mL. Two hours after inoculation, the MIN HSR was administered subcutaneously (SC) over 24h. Control mice received normal saline. Efficacy was measured as the change in log10CFU/thigh at 24h compared with 0h controls.

Results
MIN 22, 10, 14, and 10mg/kg dosed SC at 0, 6, 12, and 18h best recapitulated the human Cmax and AUC profile. Mean ± standard deviation bacterial burden at 0h across all isolates was 6.03±0.32 log10CFU/thigh. Bacterial growth was 1.35±0.68 log10CFU/thigh in 24h controls. Six of 7 isolates (86%) with MIC ≤ 0.5mg/L achieved 1-log kill with MIN HSR (-1.44±1.37 log10CFU/thigh). All STM with MIC ≥ 1mg/L experienced bacterial growth (1.18±0.79 log10CFU/thigh) (Figure).
Figure. Efficacy of a minocycline human simulated exposure of 100mg intravenous Q12h in the murine neutropenic thigh model against 17 clinical Stenotrophomonas maltophilia isolates

Conclusion
These data describe the in vivo efficacy of a MIN HSR with exposures similar to MIN 100mg IV q12h in critically ill adults. Lack of antibacterial activity against STM with MICs ≥ 1mg/L justifies a reassessment of the current susceptibility breakpoint.
The study was funded under FDA Contract 75F40120C00171.

Disclosures
David P. Nicolau, PharmD, Abbvie, Cepheid, Merck, Paratek, Pfizer, Wockhardt, Shionogi, Tetraphase (Other Financial or Material Support, I have been a consultant, speakers bureau member, or have received research funding from the above listed companies.) Joseph L. Kuti, PharmD, Allergan (Speaker’s Bureau)BioMérieux (Consultant, Research Grant or Support, Speaker’s Bureau)Contrafect (Scientific Research Study Investigator)GSK (Consultant)Merck (Research Grant or Support)Paratek (Speaker’s Bureau)Roche Diagnostics (Research Grant or Support)Shionogi (Research Grant or Support)Summit (Scientific Research Study Investigator)
72. Massive Weight Gain in People with HIV (PWH) Starting Initial Antiretroviral Therapy (ART): Risk Factors and Predictive Ability of Early Weight Gain
Authors: Phupitakphol Tanit , McEwen Dean , Hawkins Kellie , Gardner Edward 
Published: December 2021

Abstract

Background
Using a clinic cohort of ART naïve PWH, we sought to understand factors associated with massive weight gain as well as to assess if early weight gain could help predict massive weight gain at two years.

Methods
This was a retrospective cohort study of PWH from a large, urban clinic initiating first ART from January 2005 through March 2019, who had 21 – 27 months follow-up without ART changes, and were suppressed (HIV-RNA &lt; 200 cps/ml) during that time. We defined massive weight gain as the top 20% of weight gainers at two years measured by percent (%) gain compared to baseline. Using bivariate and multivariate logistic regression (including factors in bivariate analysis with p&lt; 0.20), we assessed the association of demographics, ART regimen, baseline CD4 count, HIV viral load, and body mass index (BMI) with weight gain at 2 years. We also assessed early weight gain (between 4 and 12 wks) and its association with massive weight gain at two years.

Results
Of 266 PWH included (table1), the median age was 36 years (IQR 29 - 45), 9% were women, 14% black, and 43% Latino. Overall, median % weight gain at 2 years was 4% (-1.1 – 11.6) In bivariate analyses, baseline factors significantly associated with massive weight gain included lower CD4 count, higher viral load, and lower baseline BMI. In multivariate analysis the odds of having massive weight gain were higher with lower CD4 count, adjusted odds ratio (aOR) 0.8 (95% CI 0.6 – 0.9) per 100 cells/ul increase and higher viral load, aOR 2.6 (95% CI 1.4 – 4.6) per 1 log increase. Early weights were available for 217 individuals at a median of 56 days (IQR 44 – 63) after ART initiation. Early weight gain correlated with % weight gain at 2 years (R=0.58). Individuals with ≤ 3% early weight gain represented 66% of the population and had a 10% risk (14 of 144) of having massive weight gain at 2 years. In contrast, 43 individuals had &gt; 5% early weight gain and their risk of massive weight gain at 2 years was 56% (24 of 43).

Conclusion
In this real-world dataset, drug class or specific NRTI use was not associated with massive weight gain which was primarily dependent on baseline CD4 count and HIV viral load. There was a moderate correlation between early weight gain and massive weight gain at 2 years which can help with patient counseling and interventions aimed at slowing weight gain in this population.

Disclosures
All Authors: No reported disclosures
73. Interim Resistance Analysis of Long-Acting Lenacapavir in Treatment-Naïve People with HIV at 28 Weeks
Authors: VanderVeen Laurie , Margot Nicolas , Naik Vidula , Chang Silvia , Martin Ross , Dvory-Sobol Hadas , Rhee Martin , Callebaut Christian 
Published: December 2021

Abstract

Background
Lenacapavir (LEN) is a first-in-class HIV-1 capsid (CA) inhibitor in clinical development for treatment and prevention of HIV-1 infection. CALIBRATE is an ongoing, phase 2 clinical study evaluating subcutaneous (SC) or oral LEN, in combination with other antiretrovirals, in treatment-naïve people with HIV-1. High rates of virologic success (HIV-1 RNA &lt; 50 copies/mL) were achieved with LEN-based regimens by FDA Snapshot analysis at Week 28. Here, we present interim resistance analyses through Week 28.

Methods
Participants were randomized (2:2:2:1) to treatment groups (TG) (Figure): SC LEN + oral daily emtricitabine/tenofovir alafenamide (F/TAF); at Week 28, participants switch F/TAF to oral TAF (TG-A) or bictegravir (B, BIC) (TG-B); oral daily LEN + F/TAF (TG-C), or oral daily B/F/TAF (TG-D). Genotypic analyses (population sequencing) of HIV-1 reverse transcriptase and integrase, and genotypic (deep sequencing)/phenotypic analyses for CA were performed at screening; genotypic and phenotypic analyses were conducted at confirmed virologic failure.

Figure
CALIBRATE Study Design

Results
182 participants were randomized and dosed in TG-A to D (n=52, 53, 52, 25). Most participants had subtype B HIV-1 (92.9%). Sequence analysis of baseline samples found 65% of amino acid residues were conserved with &lt; 1% variation across CA overall, and 55% of residues were fully conserved. No mutations were detected at 6 positions in CA associated with reduced susceptibility to LEN in vitro; residues were fully conserved at 5 positions (L56, M66, Q67, K70, N74), and &lt; 2% variation was observed at 1 position (T107). Three participants met the criteria for resistance analysis: 2 participants resuppressed to &lt; 50 copies/mL while continuing treatment. One participant on SC LEN + F/TAF developed emergent resistance to LEN (Q67H+K70R) and emtricitabine (M184M/I), followed by resuppression after starting dolutegravir, zidovudine + lamivudine, tenofovir disoproxil fumarate.

Conclusion
Emergent resistance to LEN was uncommon in treatment-naïve participants receiving SC or oral LEN (0.6%, 1/157). These interim resistance findings support the ongoing evaluation of LEN for treatment and prevention of HIV.

Disclosures
Laurie VanderVeen, PhD, Gilead Sciences (Employee, Shareholder) Nicolas Margot, MA, Gilead Sciences (Employee, Shareholder) Vidula Naik, MSc, Gilead Sciences (Employee, Shareholder) Silvia Chang, Masters, Gilead Sciences, Inc (Employee, Shareholder) Ross Martin, PhD, Gilead Sciences, Inc (Employee, Shareholder) Hadas Dvory-Sobol, PhD, Gilead Sciences (Employee, Shareholder) Martin Rhee, MD, Gilead Sciences (Employee, Shareholder) Christian Callebaut, PhD, Gilead Sciences (Employee, Shareholder)
76. Effects of the “Undetectable = Untransmittable” (“U=U”) Educational Campaign on Treatment Outcomes and Perceptions among People Living with HIV in North American Countries
Authors: Spinelli Frank , Richman Bruce , Rios Patricia De Los , Young Benjamin , Muchenje Marvelous , Van de Velde Nicolas , Okoli Chinyere 
Published: December 2021

Abstract

Background
The educational campaign “Undetectable = Untransmittable” (U=U) began in 2016 to improve the well-being of people living with HIV (PLHIV) and recalibrate HIV-related social norms. As medical practice can vary by region, we examined reports from PLHIV in North American countries to identify if the campaign affected healthcare provider (HCP) communication of U=U and if positive health outcomes differed by U=U-informed status or country.

Methods
Data were collected from the 2019 Positive Perspectives survey of PLHIV in Canada (n=120), Mexico (n=63), and the United States (US; n=400) and stratified by country. Outcomes were self-rated mental and sexual health (“Good”/”Very good”), viral suppression, and sharing of HIV status. Treatment perceptions were also assessed.

Results
Whether diagnosis occurred before or after the U=U campaign launch did not significantly affect the proportion of PLHIV who reported receipt of U=U from an HCP in any North American country. Whether an individual was informed of U=U varied significantly by sexual orientation (heterosexual, 62.8%; homosexual, 74.9%; other, 87.8%), sex (men, 64.7%; women, 89.8%; other, 100%), and metropolitan vs non-metropolitan residence (metropolitan, 78.2%; non-metropolitan, 65.2%) in the US (P&lt; 0.01 for all) but not in Canada or Mexico. Prevalence of sharing of HIV status with ≥ 1 person besides an HCP varied among PLHIV (Canada, 87%; Mexico, 95%; US, 84%). Prevalence of other positive outcomes varied by country and whether PLHIV had been informed of U=U (Figure). Whether PLHIV were informed of U=U was also correlated with treatment satisfaction and the perception that treatment needs were being met among PLHIV in the US and Canada (P&lt; 0.01 for all), and with the belief that treatment prevents transmission among PLHIV in the US (P=0.01).
Figure. Prevalence of positive outcomes among PLHIV in Canada (n=120), Mexico (n=63), and the US (n=400). PLHIV, people living with HIV; US, United States; U=U, Undetectable = Untransmittable. *P&lt;0.01 for U=U informed vs uninformed.

Conclusion
Being informed of U=U was associated with higher treatment satisfaction, and higher mental and sexual health outcomes among PLHIV in North America. Receipt of U=U was associated with significantly higher treatment satisfaction among PLHIV in the US and Canada, and significantly more PLHIV with optimal mental and sexual health in the US.

Disclosures
Frank Spinelli, MD, ViiV Healthcare (Employee) Bruce Richman, JD, ViiV Healthcare (Consultant) Patricia De Los Rios, MSc, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Benjamin Young, MD, PhD, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee) Nicolas Van de Velde, PhD, ViiV Healthcare (Employee) Chinyere Okoli, PharmD, MSc, DIP, GlaxoSmithKline (Shareholder)ViiV Healthcare (Employee)
78. Non-Invasive Prediction of Invasive Fungal Infection by Plasma-Based Microbial Cell-Free DNA Next-Generation Sequencing (mcfDNA NGS) in Pediatric Patients with Relapsed or Refractory Leukemia
Authors: Wolf Joshua , Wolf Joshua , Maron Gabriela , Goggin Kathryn , Allison Kim J , Merritt Pamela , griffen Amanda , Rubnitz Jeffrey , Duttagupta Radha , Brenner Abigail , Blair Lily , Ahmed Asim A , Morin Cara 
Published: December 2021

Abstract

Background
Diagnosis of invasive fungal infections (IFIs), a life-threatening complication of cancer therapy or hematopoietic cell transplantation (HCT) can be challenging, and IFI has poor outcomes. Prediction or early non-invasive diagnosis of IFI in high-risk hosts before onset of symptoms could reduce morbidity and mortality.
Because non-invasive plasma mcfDNA NGS can detect invasive fungal infections, and may predict bloodstream infections in immunocompromised patients, we hypothesized that mcfDNA NGS might also predict invasive fungal infection before clinical presentation.

Methods
In a prospective study, serial remnant plasma samples were collected from pediatric patients undergoing treatment for relapsed or refractory leukemia. IFI events were classified according to EORTC criteria by 2 independent experts, and episodes empirically treated for suspected IFI, but not meeting ‘possible’ criteria were classified as ‘suspected’. All samples collected within 30 days before clinical diagnosis of non-fungemic IFI were tested for fungal DNA by mcfDNA NGS using a research-use only assay by Karius, Inc. optimized for fungi; because of overlapping clinical syndromes, non-fungal DNA was not considered in this study.

Results
There were 15 episodes of suspected IFI in 14 participants with ≥1 sample available from either diagnostic (within 1 day of diagnosis) or predictive (2 to 30 days prior to diagnosis) periods (5 “suspected”, and 4 probable and 6 proven by EORTC definitions).
Of 10 probable or proven IFIs, 6 (60%) had a relevant fungal pathogen identified mcfDNA NGS at diagnosis. In each of these cases the fungal DNA was also detectable prior to clinical onset of IFI (Range 2 to 41 days; Figure 1). In an additional case, manual review of sequence data identified the fungal DNA at diagnosis and during the prior month. Of 5 “suspected” IFI episodes, all were determined by expert review as not representing fungal infection; fungal DNA was identified by mcfDNA NGS in 2/54 (3.7%) of samples from these episodes.
Table 1. Characteristics of Invasive Fungal Infections

Conclusion
mcfDNA NGS can identify fungal pathogen DNA before clinical onset of IFI, so might predict IFI in immunocompromised hosts, and may help differentiate fungal infection from other etiologies of lung nodules or infiltrates.

Disclosures
Joshua Wolf, MBBS, PhD, FRACP, Karius Inc. (Research Grant or Support) Joshua Wolf, MBBS, PhD, FRACP, Nothing to disclose Radha Duttagupta, PhD, Karius inc (Employee) Lily Blair, PhD, Karius Inc. (Employee) Asim A. Ahmed, MD, Karius, Inc. (Employee)
81. SARS-CoV-2 RNAemia and Disease Severity in Pediatric Coronavirus Disease 2019 (COVID-19)
Authors: Mertz Cameron , Glowinski Rebecca M , Mertz Sara , Peachey Colin L , Miller Lauren , Sanchez Pablo J , Cohen Shira H , Ye Fang , Wolfe Amber , Pifer Traci , Everhart Kathy , Ramilo Octavio , Mejias Asuncion 
Published: December 2021

Abstract

Background
Children with COVID-19 may develop severe disease. In hospitalized adults, detection of plasma SARS-CoV-2 RNAemia ranges from 19% to 42% and has been associated with worse clinical outcomes. A similar association in children remains unexplored. We determined the frequency of SARS-CoV-2 RNAemia in children hospitalized with COVID-19 and evaluated its potential association with severe disease.

Methods
Single center prospective study that enrolled hospitalized children and adolescents ≤21 years old with COVID-19 from March 2020-April 2021 at Nationwide Children’s Hospital, Columbus, OH. Nasopharyngeal (NP) and blood samples were obtained and SARS-CoV-2 RNA was quantified using a real time PCR assay targeting the N1 gene. Pertinent demographic, clinical, laboratory, and outcome data were evaluated.

Results
We enrolled a convenience sample of 103 hospitalized children (median age, 9 years; range, 3 days-21 years) who had confirmed SARS-CoV-2 infection and both NP and blood samples obtained (Table 1). Overall, 27 (26%) patients with COVID-19 had SARS-CoV-2 RNAemia. Compared with patients who had undetectable RNAemia, those with SARS-CoV-2 RNAemia had significantly higher nasopharyngeal RNA loads (8.1 vs. 4.9 log10 copies/mL; p=0.0006), fever (78 vs 54%; p=0.02), receipt of supplemental oxygen (37% vs 14%; p=0.02), and treatment with anti-COVID-19 medications (30% vs 12%; p=0.04). In addition, patients with SARS-CoV-2 RNAemia were more likely to require intensive care (40%% vs. 20%, p= 0.04) and had longer hospitalization (2.56 vs 2.15 days; p=0.03). There were no COVID-19 related deaths.
Table 1. Demographic, clinical, laboratory and virology characteristics of study patients

Conclusion
The frequency of SARS-CoV-2 RNAemia in pediatric patients was 26% and its finding was associated with worse clinical in-hospital outcomes, similar to that reported in adults. Testing for SARS-CoV-2 RNAemia in children may help identify those who could benefit from more intensive supportive care as well as antiviral and anti-inflammatory medications.

Disclosures
Octavio Ramilo, MD, Adagio (Consultant)Bill & Melinda Gates Foundation (Grant/Research Support)Janssen (Grant/Research Support)Lilly (Consultant)Merck (Consultant, Grant/Research Support)NIH (Grant/Research Support)Pfizer (Consultant)SANOFI (Board Member) Asuncion Mejias, MD, PhD, MsCS, Janssen (Grant/Research Support, Advisor or Review Panel member)Merck (Grant/Research Support, Advisor or Review Panel member)Roche (Advisor or Review Panel member)Sanofi (Advisor or Review Panel member)
83. ID Coaches Contribute to a Highly Effective Learning Experience for Third-Year Medical Students Rotating on the Infectious Diseases Consult Service
Authors: Roberts Erin , Sigler Rachel , Welford Elliott , Keehner Jocelyn , Wooten Darcy 
Published: December 2021

Abstract

Background
Education on infections in hospitalized patients, antimicrobial selection, and principles of antimicrobial stewardship are foundational to all clinicians. Incorporating early learners into Infectious Diseases (ID) consult services has the potential to build a strong fund of knowledge in these content domains, but also poses potential challenges. We evaluated the impact of a novel clinical rotation and supporting curriculum on third-year medical students rotating on the ID consult service for 2 weeks during their 12-week Internal Medicine clerkship at the University of California, San Diego.

Methods
Third-year medical students who selected to rotate on the ID consult service were given an hour-long orientation about the service and common infectious syndromes. They were provided with a checklist of clinical skills to complete during the rotation. In addition to daily rounds and clinical care, ID Coaches (ID faculty and senior ID fellows) met with students weekly for 1-2 hours to review ID topics, practice oral presentations, and/or conduct physical exam finding rounds. We surveyed medical students to assess the effectiveness of the rotation.

Results
Forty third-year medical students participated in the 2-week ID consult rotation between June 2020-May 2021; 31 (77%) completed the rotation evaluation. Seventy percent or more of students reported that the ID rotation facilitated their learning across 8 of 10 ID-content domains (Figure 1). More students reported that the ID Coach facilitated learning (71%) compared to the clinical skills checklist (42%). Students highlighted learning about antimicrobial selection, stewardship, and clinical reasoning on the rotation but reported that teaching was limited when the service census was high (Figure 2).
Figure 1: Percent of Students Rating the ID Consult Rotation as Extremely or Very Effective in Facilitating Learning Across 10 Domains

Figure 2: Students' Reflections on the Effectiveness of the ID Consult Rotation

Conclusion
Third-year medical students found that a 2-week rotation on the ID consult service was highly effective in teaching foundational ID content and general medicine skills. Incorporating early learners into a busy and complex subspecialty consult service can be facilitated through the use of supplemental curricular tools such as ID Coaches.

Disclosures
Darcy Wooten, MD, MS, Nothing to disclose
84. Paying for Parenthood: Misinterpretation of ABIM Leave Policies May Lead to Unnecessary Extension of ID Fellowships
Authors: Stead Wendy , Gardiner Catherine P , Desrochers Laura P , Finn Kathleen , McDonald Furman S , Melfe Michael , Melia Michael 
Published: December 2021

Abstract

Background
Many trainees plan pregnancy during fellowship training. A study of internal medicine program directors (PDs) demonstrated frequent misinterpretation of American Board of Internal Medicine (ABIM) leave policies when applied to parental leave. The ABIM has since attempted to clarify its leave and deficits in training policies. The primary aim of this study was to investigate how infectious disease (ID) program directors interpret the current ABIM leave policies in crafting parental leave for trainees.

Methods
We surveyed 155 ID program directors in an online, anonymous questionnaire regarding their knowledge of ABIM leave policies and application toward trainees’ leaves of absence.

Results
75/155 (48%) of program directors responded to the survey. Most respondents incorrectly identified the leave limits permitted by ABIM policies, and a majority mistakenly chose to extend training when a clinically competent fellow was within their allowed duration of leave.(Figure 1) Most respondents correctly identified that equal time is permitted for both birth and non-birth parent parental leave, however, reported leave durations did not reflect this equity. PDs reported the majority (60.4%) of ID trainee maternity/birth parent leaves at their programs were ≤7weeks and 4.6% were≤3 weeks, while only 7% were≥12 weeks. In contrast, 50% of paternity/non birth parent leaves were ≤3weeks and none were ≥12 weeks. (Figure 2) PDs utilize various strategies to prevent extending training for fellows taking parental leaves that exceed the limits allowed by ABIM policies, including creating “home electives,” though 34% counsel trainees to take “a shorter maternity leave.”

Conclusion
Fellowship program directors often misinterpret ABIM leave policies, and misapply them when given example scenarios. These findings have clear implications for trainees’ family planning and may lead to shortened parental leaves and inappropriate fellowship training extensions.

Disclosures
All Authors: No reported disclosures