Staphylococcal aureus (MRSA) is reported to Centers for Medicare and Medicaid services through the National Healthcare Safety Network (NHSN), yet few studies have described HOB-MRSA epidemiology. Thus, we report HOB-MRSA epidemiology from 2020-2022 at our multi-hospital health system to inform quality improvement initiatives.Hospital-onset bacteremia (HOB) is a quality metric proposed by CDC. HOB caused by methicillin-resistant We used data submitted to the NHSN to prospectively identify HOB-MRSA LabID cases and collected demographic and clinical characteristics from patients’ electronic medical records. Hospital epidemiologists at each of the 9 hospitals adjudicated suspected sources of HOB-MRSA. Annual standardized infection ratios (SIRs) were calculated. Characteristics of HOB-MRSA episodes were analyzed by descriptive statistics. Relevant institutional review boards deemed this study exempt from Human Subjects Research.From 2020-2022, 174 (0.029%) HOB-MRSA episodes occurred among 573,433 hospitalizations. Table 1 provides the characteristics of patients with HOB-MRSA and Table 2 provides the SIRS and suspected sources of HOB-MRSA. Overall, 43% of patients were in an ICU, 44% had a central line (CL), and 30% were on a ventilator. The SIR was lowest in 2022. Respiratory sources (non-ventilator and ventilator-associated pneumonia (VAP)) were the most common and declined over time (p=0.002). Suspected sources of HOB-MRSA were unknown for 11% of episodes.We found that episodes of HOB-MRSA were attributed to multiple primary sources of infection. Thus, bundle strategies for VAP and CL-associated bloodstream infections, while crucial, are insufficient to reduce all HOB-MRSA. In addition, prevention strategies for patients with skin and soft tissue infections are needed. Our findings highlight the importance of adherence to all device and procedure-related bundles, hand hygiene, cleaning/disinfection, and MRSA decolonization when appropriate. Elucidating the epidemiology of primary infection sources can further tailor prevention strategies for HOB.Sorana Segal-Maurer, MD, Gilead Sciences, Inc: Advisor/Consultant|Gilead Sciences, Inc: Honoraria|Janssen: Advisor/Consultant|Janssen: Honoraria|Theratechnologies: Advisor/Consultant|Theratechnologies: Honoraria|Viiv: Advisor/Consultant|Viiv: Honoraria Nishant Prasad, MD, Gilead Sciences, Inc.: Grant/Research Support Lisa Saiman, MD MPH, Merck & Co., Inc,: Grant/Research Support|Merck & Co., Inc,: Member, DSMB|Pfizer, Inc: Member, DSMB


Ventilator-associated pneumonia (VAP) is commonly overdiagnosed & a primary driver of antibiotic overuse within intensive care units (ICUs). Antimicrobial stewardship programs have successfully leveraged diagnostic stewardship interventions (DSIs) to prevent overdiagnosis/overtreatment of diverse clinical syndromes, yet this approach has not been extended to VAP. In this trial, we aimed to evaluate the safety, feasibility & efficacy of a novel DSI care bundle (DSI-CB) targeting VAP.The DIVA trial (NCT05176353) was a pilot/feasibility trial conducted in 2 ICUs at Michigan Medicine from February 2022-February 2023. A DSI-CB targeting the respiratory culture testing pathway was implemented sequentially in study ICUs, using an interruptive electronic health record clinical decision support tool & modifications to microbiology laboratory workflows (Table 1). Providers were counseled on DSI-CB use during bimonthly educational sessions during trial rollout & via monthly email reminders thereafter. Rates of prespecified co-primary safety and secondary efficacy outcomes were compared between the postintervention study cohort & 5-year preintervention historical controls using negative binomial regression. Interrupted time series analysis was used to evaluate ICU antibiotic utilization rates (ICU-AURs) to account for temporal trends.1810 patients were admitted to study ICUs following DSI-CB implementation, 29% of whom were eligible for DSI-CB use. DSI-CB was utilized in 77% of eligible patients. Patient demographics, comorbidities & measures of acute severity of illness were similar pre- & post-intervention. DSI-CB implementation was not associated with increases in primary adverse safety outcomes (Table 2). DSI-CB implementation was associated with significant reductions in rates of total respiratory cultures ordered, rates of positive respiratory cultures & reductions in both total & broad-spectrum ICU-AURs .Implementation of a novel VAP DSI-CB was safe, feasible & associated with significant reductions in rates of respiratory culture positivity and ICU-AURs. This represents the first trial of a DSI targeting VAP & a novel avenue for ICU antimicrobial stewardship. Large-scale trials are warranted.Owen Albin, MD, Biomeriux: Grant/Research Support|Charles River Laboratories: Advisor/Consultant|Shionogi: Advisor/Consultant Weirauch J. Andrew, RRT, Drager Medical: Equipment loaned for research purposes, but no monetary funds were provided.|Jones and Bartlett Learning: Honoraria Krishna Rao, MD, MS, Merck & Co.: Grant/Research Support|Rebiotix: Advisor/Consultant|Seres Therapeutics: Advisor/Consultant|Summit Therapeutics: Advisor/Consultant Keith S. Kaye, MD, MPH, Entasis: Advisor/Consultant|Entasis: Honoraria|GSK: Advisor/Consultant|GSK: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|Shionogi: Advisor/Consultant|Shionogi: Honoraria|VenatoRx: Advisor/Consultant|VenatoRx: Honoraria


Prevention of severe respiratory syncytial virus (RSV) disease in people at high risk for severe RSV infection  is a significant unmet medical need. Data are sparse on the natural history  of the infection in patients initially managed in the outpatient setting. To address this gap, the natural history of RSV infection in outpatient adults was examined in a real-world electronic health record (EHR) data source with daily data updates, enabling analysis of the current season.In US-based Truveta EHR database, adults with a positive RSV laboratory test result  in the outpatient setting (emergency department (ED), office/clinic, or urgent care) were identified and excluded if immediately hospitalized (within 24 hours of index). To accurately capture preexisting comorbidities, patients were required to have at least one healthcare encounter in the 6 months prior to index. Analyses were stratified by time: pre-COVID-19 (2017-2019), COVID-19 (2020-2021), and current season (2022-January 2023) and restricted to health systems participating for the entire study period. Occurrences of all-cause hospitalization, ED visits, and pneumonia were assessed during 28 days of follow-up (index not included), stratified by risk factors .Among the 6 health systems, 5,807 adults were identified from 2017-2023. Mean ages (standard deviation) were as follows: 52 (20) years (2017-2019); 52 (20) years (2020-2021); 62 (18) years (2022-January 2023). Hospitalization proportions ranged from 7.2-13.2% for all older adults (≥65 years) and were approximately 50% lower when restricting to older adults without other risk factors (Table 1). Expanding to adults 18+ years with risk factors brought hospitalization proportions to 5.7-10.4% (Table 1).The proportion of high risk adults hospitalized ranged from 3.3-13.2%, with substantial variation by period. Future analyses will include expansion of the study period to include the entire 2022-2023 season and validation in other EHRs in the US.Diana Garofalo, PhD MPH, Pfizer: Stocks/Bonds Joshua T. Swan, PharmD, MPH, BCPS, FCCM, CareDx: Grant/Research Support|Genentech: Grant/Research Support|Grifols Share Services North America: Grant/Research Support|Heron Therapeutics: Grant/Research Support|Kedrion Biopharma: Advisor/Consultant|Kedrion Biopharma: Grant/Research Support|Pacira Pharmaceuticals: Grant/Research Support|Pfizer: Grant/Research Support|Pfizer: Employee|Pfizer: Stocks/Bonds|VigiLanz Corporation: Grant/Research Support Margaret Tawadrous, MD, MS, Pfizer: Full time employee|Pfizer: Full-time employee|Pfizer: Full-time employee|Pfizer: Full -time employee|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Ownership Interest|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Glenn Pixton, MS, Abbott: Stocks/Bonds|Abbvie: Stocks/Bonds|Pfizer: employee|Pfizer: Stocks/Bonds|Viatris: Stocks/Bonds Stephen E. Schachterle, Pfizer Inc., Pfizer Inc.: Full time employee|Pfizer Inc.: Ownership Interest|Pfizer Inc.: Stocks/Bonds Suzanne Landi, PhD, Pfizer, Inc: Employment|Pfizer, Inc: Stocks/Bonds Sudeepta Aggarwal, Ph.D, Pfizer: Employee of and may hold stock/stock options in Anindita Banerjee, Phd, Pfizer: Employee and stockholder Niki Alami, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Scott P. Kelly, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds


SARS-CoV-2 has changed and mutated over time. It is important to evaluate changes in clinical presentation and outcomes based on the emerging variants. In this study, we aimed to compare differences in symptoms and outcomes among adults hospitalized with COVID-19 by variant.From May 2021 to August 2022, we enrolled adults ≥ 18 years of age hospitalized with acute respiratory infection (ARI) at two Emory University hospitals. Demographic and clinical information were obtained from participant interviews and medical chart abstractions. Enrolled patients provided nasopharyngeal and oropharyngeal swabs and standard-of-care specimens. Samples which tested positive for SARS-CoV-2 by molecular testing were subjected to SARS-CoV-2 targeted spike SNP PCR and viral genome sequencing to determine a variant. Statistical analysis was performed using SAS version 9.4. Bivariable analyses were conducted to compare characteristics and identify independent characteristics associated with each variant.Of 1677 ARI enrolled participants, 850 tested positive for SARS-CoV-2, of whom 592 had a variant identified by either SNP PCR or full genome sequencing. The distribution of variants among these cases were as follows: 39 Alpha (6.6%), 2 Beta (0.3%), 307 Delta (51.9%), 9 Gamma (1.5%), 5 Mu (0.8%), and 230 Omicron (38.9%). When analysis was limited to participants with Alpha, Delta, or Omicron, those with Omicron were significantly older, white, female, and had underlying comorbidities. Compared to participants with Alpha and Delta, those with Omicron more often had sore throat and abdominal pain, but less often had fever, diarrhea, anosmia, ageusia, or shortness of breath. Also, those with Omicron were more often partially or fully vaccinated, with the majority of Omicron infections occurring after vaccination (Table 1). Most clinical outcomes were better among those with Omicron infections, while participants with Delta had the highest proportion of radiographic pneumonia, mechanical ventilation, and death (Table 1).SARS-CoV-2 variants were associated with distinct clinical characteristics and outcomes, and the Delta variant was associated with the highest frequency of pneumonia, mechanical ventilation, and death.Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Srinivas Valluri, PhD, Pfizer Inc: Pfizer Employee and hold Pfizer stocks/options|Pfizer Inc: Ownership Interest|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Satoshi Kamidani, MD, CDC: Grant/Research Support|Emergent BioSolutions: Grant/Research Support|NIH: Grant/Research Support|Pfizer Inc: Grant/Research Support Evan J. Anderson, MD, GSK: Advisor/Consultant|GSK: Grant/Research Support|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Kentucky Bioprocessing, Inc.: Safety Monitoring Board|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Moderna: Currently an employee|Moderna: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant|Sanofi Pasteur: Grant/Research Support|Sanofi Pasteur: Safety Monitoring Board|WCG/ACI Clinical: Data Adjudication Board Christina A. Rostad, MD, BioFire Inc.: Grant/Research Support|GlaxoSmithKline Biologicals: Grant/Research Support|Janssen: Grant/Research Support|MedImmune LLC: Grant/Research Support|Meissa Vaccines, Inc.: RSV vaccine technology|Merck & Co., Inc.: Grant/Research Support|Micron Technology, Inc.: Grant/Research Support|Moderna, Inc.: Grant/Research Support|Novavax: Grant/Research Support|PaxVax: Grant/Research Support|Pfizer, Inc.: Grant/Research Support|Regeneron: Grant/Research Support|Sanofi Pasteur: Grant/Research Support


Community-acquired alveolar pneumonia (CAAP) is considered a bacterial disease in most cases. However, multiple studies in young children have shown a high correlation of its incidence with the epidemiological activity of four respiratory viruses . This strongly suggests an important role for bacterial-viral coinfections. The current study examines the detection rate of PAV in radiologically-confirmed CAAP in young children.Hospitalization for CAAP episodes and viral detection were prospectively studied among all children under 5 years living in southern Israel (the Negev district); over 95% of these children are born and treated at the only medical center in the region. This prospective active surveillance was previously described . Viral activity was defined by all PAV-positive tests in children under 5 years in the community. Nasal samples of children with CAAP were obtained for virus detection by PCR within 48 hours from admission. Only episodes tested for all four PAVs were included. The monthly incidence of PAV-positive CAAP was calculated by extrapolating to all-CAAP episodes, in each month.Table). Overall, 59% of all episodes were positive for one or more PAVs, 64% of which were RSV (either as single or mixed detection). The surveillance of PAV activity in the community yielded 9,021 positive specimens for one or more PAVs. The dynamic patterns of both all-cause and PAV-positive CAAP hospitalizations from July 2016 through December 2022 closely resembled that of the PAV activity in the community, including the unusual pattern during the COVID-19 years 2020 through 2022 . The PAV-CAAP episodes were the main contributors of the CAAP seasonality .During the study period, 2,592 CAAP hospitalizations occurred. Specimens for all four PAVs were obtained in 1,851 (71.4%) CAAP episodes  (RSV, followed by hMPV, and to a lesser degree influenza and parainfluenza viruses, were the main viruses detected in children under 5 years hospitalized for CAAP. These four viruses were responsible for the seasonal pattern of CAAP hospitalizations.Ron Dagan, Professor MD, GSK: Honoraria|MedIMmune/AstraZeneca: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Expert Testimony|Pfizer: Grant/Research Support|Pfizer: Honoraria|Sanofi Pasteur: Honoraria David Greenberg, Professor MD, GSK: Advisor/Consultant|GSK: Honoraria|MSD: Advisor/Consultant|MSD: Grant/Research Support|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Honoraria Shalom Ben-Shimol, Dr. MD, GSK: Honoraria|MSD: Advisor/Consultant|MSD: Honoraria|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: Honoraria Daniel M. Weinberger, PhD, GSK: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support Dana Danino, Dr. MD, Pfizer: Grant/Research Support


COVID-19 vaccines in pregnancy protect both pregnant individuals and young infants from severe illness via transplacental transfer of maternally-derived IgG. However, the impact of multiple (e.g. twin) pregnancy on transplacental transfer of SARS-CoV-2 IgG is unknown. We aimed to evaluate anti-Spike (S) antibody transfer among infants from twin pregnancies compared to singleton pregnancies.th percentile) birthweight.We conducted a prospective cohort study among individuals with twin and singleton pregnancies who received at least 2 doses of an mRNA COVID-19 vaccine prior to delivery. We tested paired maternal and cord samples for anti-S IgG and used linear regression to evaluate associations between multiple or singleton pregnancy and anti-S antibody. We included as covariates timing of last vaccine dose, gestational age at delivery, number of doses prior to delivery, and small for gestational age  and 2971 BAU/mL  for twin and singleton pregnancies, respectively. Median cord anti-S IgG was 4110 BAU/mL  and 3636 BAU/mL  for twin and singleton infants, respectively . Cord:maternal IgG ratios were significantly lower in twin pregnancies compared to singleton pregnancies . After adjustment for covariates, there was no difference between maternal anti-S IgG concentrations , cord anti-S IgG concentrations  or cord:maternal IgG ratios  between twin and singleton pregnancies.Twin and singleton infants benefit similarly from maternal COVID-19 vaccine during pregnancy. Higher risk pregnancies including multiple pregnancies should be considered in health policy discussions regarding COVID-19 vaccine timing in pregnancy.Alisa B. Kachikis, MD, MSc, Merck: Grant/Research Support|Pfizer: Grant/Research Support Mindy Pike, PhD, Merck: Grant/Research Support Alexander L. Greninger, MD, PhD, Cepheid: central contracts|Hologic: central contracts|Janssen: central contracts|Novavax: central contracts|Pfizer: central contracts Janet A. Englund, MD, Ark Biopharma: Advisor/Consultant|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Meissa Vaccines: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Sanofi Pasteur: Advisor/Consultant


Staphylococcus aureus (SA) infections, both methicillin-susceptible and methicillin-resistant , cause significant morbidity among infants in neonatal intensive care units (NICU). Colonization usually precedes infection. We studied the molecular epidemiology of SA colonization in NICU infants using whole genome sequencing (WGS) and in relation to the opening of a new NICU with single-family rooms.From 2019-22, a prospective cohort of infants admitted to the Level IV NICU at Mayo Clinic, Rochester, MN was screened twice weekly for SA colonization using cultures of nares/axilla/groin swabs. Infection control procedures were consistent throughout, including use of Contact Precautions for infants colonized with MRSA but not for MSSA. The study was divided into period 1 (1/1/2019-11/30/2020) and period 2 (12/1/2020-12/31/2022) due to a move from a 34-bed unit (26 beds in four open-bay rooms and 8 beds in single-family rooms) to a new 34-bed unit . WGS was performed using Illumina MiSeq instrumentation and chemistry with Illumina Nextera XT library chemistry. Assembly and core genome multilocus sequence typing analysis were performed with Ridom SeqSphere+ software. Groups of related isolates were identified based on the number of allelic differences . Groups of MRSA-related isolates were compared with reference USA genotypes. Chi square tests did not adjust for clustering.There were 663 admissions in period 1 and 730 in period 2. The prevalence of MSSA and MRSA colonization was unchanged in the two periods . By WGS, most MSSA and MRSA isolates were unrelated to another isolate in both periods (Table). Groups of related MSSA and MRSA isolates differed between the two periods and the number of isolates/group was small (< 6 isolates). Groups of related MRSA isolates were associated with reference genotypes USA100 (period 1), USA1000 (periods 1 & 2), and USA300 (period 2).WGS Results for MSSA and MRSA in Periods 1 and 2NICU infants were usually colonized with unrelated strains of MSSA and MRSA, with only small clusters of related strains. The new NICU was not associated with a change in MSSA or MRSA colonization.Priya Sampathkumar, MD, Merck Vaccines: Advisor/Consultant Robin Patel, MD, Abbott Laboratories: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Adaptive Phage Therapeutics: Mayo Clinic has a royalty-bearing know-how agreement and equity in Adaptive Phage Therapeutics.|BIOFIRE: Grant/Research Support|CARB-X: Advisor/Consultant|ContraFect: Grant/Research Support|Day Zero Diagnostics: Advisor/Consultant|HealthTrackRx: Advisor/Consultant|Mammoth Biosciences: Advisor/Consultant|Netflix: Advisor/Consultant|Oxford Nanopore Technologies: Advisor/Consultant|PhAST: Advisor/Consultant|See details: Patent on Bordetella pertussis/parapertussis PCR issued, a patent on a device/method for sonication with royalties paid by Samsung to Mayo Clinic|See details: continued, patent on an anti-biofilm substance issued|TenNor Therapeutics Limited: Grant/Research Support|Torus Biosystems: Advisor/Consultant|Trellis Bioscience, Inc.: Advisor/Consultant W. Charles Huskins, MD, MSc, ADMA Biologics: Advisor/Consultant|Bristol Myers Squibb: Stocks/Bonds|Pfizer: Advisor/Consultant|Pfizer: Stocks/Bonds|Zimmer Biomet: Stocks/Bonds


Influenza virus infections are common in children and lead to numerous ED visits each year. The Infectious Diseases Society of America, American Academy of Pediatrics, and the Centers for Disease Control and Prevention recommend outpatient antiviral treatment for children at increased risk of severe influenza illness  and recommend treatment within 48-hours of symptom onset. We describe antiviral prescription in children presenting to the ED with influenza from 2016-2020.We analyzed data from NVSN, a prospective seven-site acute respiratory illness surveillance study. We enrolled children presenting to the ED with confirmed influenza by research molecular testing, stratified by children at increased risk of severe influenza and with symptom onset ≤ 48-hours. We compared characteristics of children who were prescribed antivirals to those who were not. We used logistic regression to compare the odds of prescription, adjusting for age, gastrointestinal symptoms, symptom duration, underlying conditions, clinical testing before antiviral prescription, and site.Table). Odds of prescription were higher for those clinically tested for influenza and for those with underlying respiratory and cardiovascular conditions, and lower for those who were younger, presented with diarrhea, and had longer duration since symptom onset .Of the 16,822 children presenting in the ED and tested for influenza, 2,387 (14%) tested positive. Among influenza positive cases, 1,873 (79%) were defined as children at increased risk of severe influenza, and 571 (30%) were prescribed an antiviral. Additionally, there were 281 (12%) children with symptom onset ≤ 48-hours, and only 70 (25%) were prescribed an antiviral , FIDSA, FAAM, Abbott: Honoraria|Altona Diagnostics: Grant/Research Support|Baebies Inc: Advisor/Consultant|BioMerieux: Advisor/Consultant|BioMerieux: Grant/Research Support|Bio-Rad: Grant/Research Support|Cepheid: Grant/Research Support|GSK: Advisor/Consultant|Hologic: Grant/Research Support|Lab Simply: Advisor/Consultant|Luminex: Grant/Research Support Natasha B. Halasa, MD, MPH, Merck: Grant/Research Support|Quidell: Grant/Research Support|Quidell: donation of kits|Sanofi: Grant/Research Support|Sanofi: vaccine support


Treatment options for mucocutaneous herpes simplex virus infections (HSV) refractory or resistant (r/r) to acyclovir (ACV) are limited. High-dose ACV continuous infusion, foscarnet (FCN), cidofovir (CDV), and/or topical agents have been used. We report treatment patterns and outcomes of r/r HSV after allogeneic hematopoietic cell transplantation (HCT).Ault HCT recipients with r/r HSV at MSKCC from 1/1/2013 through 7/31/2022 were analyzed. HSV was diagnosed by dermal PCR. Antiviral susceptibility was performed at ARUP laboratories  at clinicians’ discretion. The 50% inhibitory concentration for ACV was 2 ug/mL and for FCN 100 ug/mL. Standard care prophylaxis was ACV 400mg orally twice daily. Refractory HSV was defined as mucocutaneous HSV and failure to improve clinically after at least 7 days of standard treatment doses ACV, famciclovir, or valacyclovir and required ≥7 days of ACV ≥30mg/kg over 24 hours, FCN or CDV ≥1 dose. Resistant HSV was defined as refractory plus phenotypic resistance to ACV or FCN.Fifteen patients met the criteria for r/r HSV  (Table 1). Virologic diagnosis for HSV occurred at a median of 74 days  post-HCT. Clinical definition for r/r HSV was a median of 86 days  of post-HCT. Twelve had confirmed ACV resistance. All with r/r HSV required hospitalization for parenteral antivirals. Twelve (80%) had resolution of lesions after a median of 35 days  of treatment and 3 (20%) had persistent lesions. Ten (67%) developed recurrence  after ≥2 weeks of oral maintenance therapy. Antiviral treatment is shown in Figure 1. Five (33.3%) experienced FCN-related side effects. One received Pritelivir (PTV) under an expanded access program due to persistent lesions despite being on FCN and topical CDV.One in 5 (20%) with r/r HSV failed to resolve with currently available therapies; 67% had a recurrence of r/r HSV after stopping treatment and 27% had nephrotoxicity due to FCN. One was treated successfully with PTV, an oral investigational antiviral without cross-resistance to ACV, FCN or CDV. Our data highlight the unmet need for effective, safe, and oral bioavailable antivirals for r/r HSV after HCT.Yeon Joo Lee, MD, MPH, AiCuris: institutional research support for clinical trials|Karius: institutional research support for clinical trials|Merck: Grant/Research Support|Scynexis: institutional research support for clinical trials Miguel Perales, MD, Adicet: Honoraria|Allogene: Honoraria|Allogene: institutional research support for clinical trials|Allovir: Honoraria|Bristol-Myers Squibb: Honoraria|Caribou Biosciences: Honoraria|Celgene: Honoraria|Cidara Therapeutics: Board Member|Equilium: Honoraria|Exevir: Honoraria|ImmPACT Bio: Honoraria|Incyte: Honoraria|Incyte: institutional research support for clinical trials|Karyopharm: Honoraria|Kite/Gilead: Honoraria|Kite/Gilead: institutional research support for clinical trials|Medigene: Board Member|Merck: Honoraria|Miltenyi Biotec: Honoraria|Miltenyi Biotec: institutional research support for clinical trials|MorphoSys: Honoraria|Nektar Therapeutics: Honoraria|Nektar Therapeutics: institutional research support for clinical trials|NexImmune: Board Member|NexImmune: Ownership Interest|Novartis: Honoraria|Novartis: institutional research support for clinical trials|Omeros: Honoraria|Omeros: Ownership Interest|OrcaBio: Honoraria|OrcaBio: Ownership Interest|Sellas Life Sciences: Board Member|Syncopation: Honoraria|VectivBio AG: Honoraria|Vor Biopharma: Honoraria Genovefa Papanicolaou, MD, Allovir: Advisor/Consultant|Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|DSMC: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: institutional research support for clinical trials|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Partners Rx: Advisor/Consultant|Shire/Takeda: institutional research support for clinical trials|Symbio: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Vera Pharma: Advisor/Consultant


Cephalexin (LEX), cefuroxime axetil (CXM), and cefpodoxime (CPD) are common oral cephalosporins used to treat gram-positive and gram-negative infections. However, there is a paucity of PK/PD analyses to inform optimal dosing regimens, which drug may be preferred for a particular organism, and the susceptibility testing interpretive criteria (STIC) that may apply to help clinicians in their selection.E. coli (EC) and 5 S. aureus (SA) clinical strains were used. MICs were determined by CLSI methods. Pharmacokinetics of LEX, CXM, and CPD were performed in mice at 10, 40, 160, and 320 mg/kg. Dose-ranging efficacy studies were performed against all strains (dose range 2.5-320 mg/kg/4h). Treatment outcome was determined by organism burden in the thighs (CFU) at the end of each experiment (24 h). The dose-response (D-R) data was analyzed using the Emax Hill equation. Data was fit to the PK/PD index time above MIC (T >MIC) for free drug concentrations. Static and cidal target exposures were calculated for each strain, and targets compared by One Way ANOVA.5 2 0.66-0.91). Summary statistics for PK/PD analyses are shown in Figure.EC MIC ranges: LEX 4-64mg/L, CXM 1-8 mg/L, CPD 0.125-8 mg/L. SA MIC ranges: LEX 2-16 mg/L, CXM 0.5-2 mg/L, CPD 2-8 mg/L. All three drugs performed similarly well against SA with relatively steep D-R curves and achieving >1-log kill against 5 of 5 strains. For EC studies, LEX demonstrated a flat, more muted effect with only 2 of 5 strains achieving a 1-log kill. Comparatively, CXM and CPD demonstrated a steeper, more potent D-R curve against EC with a >1-log kill against 4 of 5 strains for CXM and 5 of 5 for CPD. The PK/PD index T >MIC fit the treatment efficacy data well (Rst-3rd generation cephalosporins exhibited efficacy against SA and EC in the mouse thigh infection model. Stasis and 1-log kill targets for the three drugs against SA were 25-35% and 35-45% T >MIC, respectively. Lower targets were noted for 1st generation LEX. PK/PD targets for stasis and 1-log kill for EC were 40-50% and 45-75% T >MIC, respectively. Lower targets were noted for 2nd generation CXM. These studies will be integral in evaluation of PK/PD target attainment by integrating human population PK for standard dosing regimens of each drug and MIC distribution data.Oral 1Sujata M. Bhavnani, PharmD; MS; FIDSA, Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Ownership Interest|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Catharine Vincent, Ph.D., Adagio Therapeutics: Grant/Research Support|Albany Medical College: Grant/Research Support|Amplyx Pharmaceuticals: Grant/Research Support|AN2: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics: Grant/Research Support|B. Braun Medical: Grant/Research Support|Basilea: Grant/Research Support|BioFire Diagnostics: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone: Grant/Research Support|CXC: Grant/Research Support|Debiopharma International SA: Grant/Research Support|Entasis: Grant/Research Support|Genentech: Grant/Research Support|GSK: Grant/Research Support|Hoffman-La Roche: Grant/Research Support|Inotrem: Grant/Research Support|Insmed: Grant/Research Support|Iterum Therapeutics: Grant/Research Support|Kaizen Bioscience: Grant/Research Support|KBP Biosciences: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma: Grant/Research Support|Melinta: Grant/Research Support|Menarini Ricerche: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics: Grant/Research Support|Paratek Pharmaceuticals: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|Univ of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics: Grant/Research Support|VenatoRx: Grant/Research Support Brian D. VanScoy, B.S., Adagio Therapeutics, Inc.: Grant/Research Support|Albany Medical Center: Grant/Research Support|Amplyx Pharmaceuticals, Inc.: Grant/Research Support|AN2 Therapeutics: Grant/Research Support|Antabio SAS: Grant/Research Support|Arcutis Biotherapeutics, Inc.: Grant/Research Support|B. Braun Medical Inc.: Grant/Research Support|Basilea Pharmaceutica: Grant/Research Support|BioFire Diagnostics LLC: Grant/Research Support|Boston Pharmaceuticals: Grant/Research Support|Cidara Therapeutics Inc.: Grant/Research Support|Cipla USA: Grant/Research Support|Crestone Inc.: Grant/Research Support|CXC: Grant/Research Support|Debiopharm International SA: Grant/Research Support|Entasis Therapeutics: Grant/Research Support|Genentech: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Hoffmann-La Roche: Grant/Research Support|ICPD: Employee|Inotrem: Grant/Research Support|Insmed Inc.: Grant/Research Support|Iterum Therapeutics Limited: Grant/Research Support|Kaizen Bioscience, Co.: Grant/Research Support|KBP Biosciences USA: Grant/Research Support|Matinas Biopharma: Grant/Research Support|Meiji Seika Pharma Co., Ltd.: Grant/Research Support|Melinta Therapeutics: Grant/Research Support|Menarini Ricerche S.p.A.: Grant/Research Support|Mutabilis: Grant/Research Support|Nabriva Therapeutics AG: Grant/Research Support|Paratek Pharmaceuticals, Inc.: Grant/Research Support|Qpex Biopharma: Grant/Research Support|Sfunga Therapeutics: Grant/Research Support|Spero Therapeutics: Grant/Research Support|Suzhou Sinovent Pharmaceuticals Co.: Grant/Research Support|Theravance: Grant/Research Support|tranScrip Partners: Grant/Research Support|University of Wisconsin: Grant/Research Support|Utility Therapeutics: Grant/Research Support|ValanBio Therapeutics Inc.: Grant/Research Support|VenatoRx: Grant/Research Support Helio S. Sader, MD, PhD, FIDSA, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support David Andes, MD, Astellas: Advisor/Consultant|Sfunga: Advisor/Consultant


Prevention of healthcare-associated infections (HAI), like surgical site infections (SSIs), has become a top priority for the medical community. Reduction of the bioburden on the skin is a proven strategy that minimizes SSI. All the currently available antiseptic skin products, for skin decolonization, are chlorhexidine gluconate (CHG) based. The rise in resistance of organisms to CHG, increase in reported cases of CHG hypersensitivity, and the lack of activity of CHG against some common pathogens, prompted us to design a novel skin antiseptic solution.In vitro time to kill assay was conducted according to ASTM protocol E2315-16. We reported CFU/ml at 3 different timepoints after exposure . The baseline inoculum for all the 16 reference strains was 105 CFU/ml. We included 8 Gram-positive, 5 Gram-negative, 2 anaerobes, and 1 fungal species. Experiments were performed two times in triplicate.The antiseptic solution tested contained benzalkonium chloride (BZK) at 0.129% as the main ingredient. Staphylococcus aureus (ATCC 29213) and Candida albicans (ATCC 18804). In fact, we observed a 2-log reduction in S. aureus (83.3 ± 98.3 CFU/ml) and almost 1-log reduction in C. albicans (1 867 ± 417.9 CFU/ml), from the baseline inoculum. After 30s of exposure, all bacterial strains were killed by the testing solution; however, C. albicans was still found at 120s of exposure (666.7 ± 535.4 CFU/ml).At 30s of exposure, only 2 out of the 16 strains tested (12.5%) remained viable: In vitro efficacy of a CHG-based and a BZK-based solution at 3 different timepoints .The BZK-based solution was effective against all Gram-positive, Gram-negative, and anaerobic bacterial strains, after 30s of exposure. The rapid action of BZK, together with its proven safety, makes it a promising product for skin decolonization in the future.Javad Parvizi, MD, FRCS, 3M: Grant/Research Support|Acumed, LLC: Stocks/Bonds|Aesculap: Grant/Research Support|Alphaeon: Stocks/Bonds|AO Spine: Stocks/Bonds|Becton Dickenson: Advisor/Consultant|Biomet: Grant/Research Support|Cardinal Health: Advisor/Consultant|Cempra: Grant/Research Support|CeramTec: Grant/Research Support|Ceribell: Stocks/Bonds|Coracoid: Stocks/Bonds|Corentec: Advisor/Consultant|Datatrace: Grant/Research Support|DePuy: Grant/Research Support|Elsevier: Grant/Research Support|Elute: Stocks/Bonds|Ethicon: Advisor/Consultant|Hip Innovation Technology: Stocks/Bonds|Illuminus: Stocks/Bonds|Integra: Grant/Research Support|Intellijoint: Stocks/Bonds|Jaypee Publishers: Grant/Research Support|KCI / 3M (Acelity): Advisor/Consultant|Lima: Grant/Research Support|MicroGenDx: Advisor/Consultant|Molecular Surface Technologies: Stocks/Bonds|Myoscience: Grant/Research Support|Nanooxygenic: Stocks/Bonds|National Institutes of Health (NIAMS & NICHD): Grant/Research Support|NDRI: Grant/Research Support|Novartis: Grant/Research Support|OREF: Grant/Research Support|Orthospace: Grant/Research Support|Osteal: Stocks/Bonds|Parvizi Surgical Innovations and Subsidiaries: Stocks/Bonds|Peptilogic: Stocks/Bonds|Peptilogics: Advisor/Consultant|Pfizer: Grant/Research Support|PRN-Veterinary: Grant/Research Support|Rotation Medical: Grant/Research Support|Simplify Medical: Grant/Research Support|SLACK Incorporated: Grant/Research Support|Smith & Nephew: Grant/Research Support|Sonata: Stocks/Bonds|Stelkast: Grant/Research Support|Stryker: Grant/Research Support|Synthes: Grant/Research Support|Tenor: Advisor/Consultant|TissueGene: Grant/Research Support|Tornier: Grant/Research Support|Wolters Kluwer Health - Lippincott Williams & Wilkins: Grant/Research Support|Zimmer Biomet: Advisor/Consultant|Zimmer Biomet: Grant/Research Support


Staphylococcus aureus (MSSA) is one of the leading causes of pediatric musculoskeletal (MSK) infections, such as osteomyelitis and septic arthritis. MSSA MSK infections are treated initially with an IV antibiotic, followed by prolonged oral therapy. Cephalexin is the most used oral option due to long-standing clinical experience and its well-described pharmacokinetics (PK) in children. Cefadroxil could be an attractive alternative requiring less frequent dosing, but it has minimal pediatric clinical or PK data. In this study, we describe the comparative PK of cephalexin and cefadroxil in children with MSK infections and evaluate dosing regimens to achieve effective free time above the MIC (fT >MIC) for MSSA.Methicillin-susceptible Children aged 6 months to 18 years admitted with an MSK infection were enrolled in a prospective, open-label, crossover study and given single oral doses of cefadroxil  and cephalexin . During a single dosing interval, 4-5 plasma samples were obtained per patient for each drug. Antibiotic concentrations were quantified using liquid chromatography-mass spectrometry. PK models were developed, and then Monte Carlo simulations were performed using various dosing regimens to estimate the probability of target attainment (PTA) for a range of pharmacodynamic (PD) targets, across various pediatric ages and common MSSA MICs (1-4 mg/L).Concentration-time data for cephalexin (n=15) and cefadroxil (n=14) were best described using a one-compartment model with first order absorption. PK parameters were notable for cefadroxil’s longer half-life than cephalexin. Monte Carlo simulation showed that cephalexin 120 mg/kg/day divided q8hrs  and cefadroxil 100 mg/kg/day divided q12hrs  achieved >95% PTA for fT >MIC >40% for MICs up to 4 mg/L, though cephalexin QID and cefadroxil TID dosing were required to achieve higher PD goals.Among pediatric patients with MSK infections, oral cefadroxil and cephalexin both achieve PD targets for efficacy against MSSA. Twice-daily cefadroxil should be further considered as an alternative to cephalexin for oral step-down therapy given its similar PTA and possibility for less frequent dosing.Marc H. Scheetz, PharmD, MSc, Abbvie: Advisor/Consultant|ASHP: Honoraria|Chambless, Higdon, Richardson, Katz & Griggs, LLP: Expert Testimony|Cidara: Advisor/Consultant|Entasis: Advisor/Consultant|F2G: Advisor/Consultant|GSK: Advisor/Consultant|Guidepoint Global: Honoraria|Hall, Booth, Smith, P.C.: Expert Testimony|Merck: Advisor/Consultant|Reminger Co., L.P.A: Expert Testimony|Spero: Advisor/Consultant|Takeda: Advisor/Consultant|Taylor, English, Duma, LLP: Expert Testimony|Third Pole Therapeutics: Advisor/Consultant Sarah K. Parker, MD, Pfizer: Grant/Research Support


Invasive meningococcal disease (IMD) serogroups A, B, C, W, Y are commonly prevented by MenACWY and MenB vaccines. MenABCWY candidate vaccines could potentially provide benefits as less injections, simplified schedules, and increased uptake. However, there is limited insight on factors influencing preferences for IMD vaccines/vaccination (Vax). This targeted literature review synthesized evidence of factors influencing IMD Vax preferences in 16–23-year-old adolescents/young adults (Ado/YA) and parents/caregivers (P/CG) of 16-18 year-old adolescents.PubMed and Google Scholar were searched globally to identify publications on IMD Vax attitudes and preferences (Table 1). Studies were restricted to English and published between 2005-2022. Data were extracted and synthesized from full text reviews to list IMD Vax preference attributes.From the 77 abstracts screened, 19 publications were extracted (Table 2) and 17 relevant for Ado/YA and P/CG. Knowledge of disease severity (20% of Ado/YA articles) and vaccine (29% of P/CG articles) were the most reported factors influencing Vax preference. Severity of disease increased Vax preference for both groups (14%), while low disease awareness limited P/CGs’ willingness to vaccinate children (14% of P/CG articles). Some Ado/YA preferred fewer injections in the immunization series due to reduced injection site discomforts (13%). P/CG preferred less injections due to less time and less physician visits, as it may reduce vaccine preparation/injection/administration and indirect costs associated with parental work loss (7%). However, their concerns over injection-related pain were a Vax barrier (14%). IMD vaccine effectiveness was recognized by Ado/YA (13%). Longer duration of protection was important for P/CG (14%), whilst herd immunity and direct protection was preferred in Ado/YA (13%).Findings highlight IMD Vax characteristics as key considerations among Ado/YA and P/CG when making Vax decisions. To improve vaccination coverage and protection, the evidence supports preferences for vaccinations offering benefits such as fewer injections. Trade-offs between factors relevant for a IMD combination vaccine need further research.Shahina Begum, GSK: Employee Eliazar Sabater Cabrera, PhD, GSK: Employee|GSK: Stocks/Bonds Oscar Herrera-Restrepo, PhD, GSK: Stocks/Bonds Twinkle Khera, Mtech, IQVIA: Advisor/Consultant Willings Botha, PhD, IQVIA: Advisor/Consultant Laurie Batchelder, PhD, IQVIA: Advisor/Consultant Zeki Kocaata, PhD, GSK: Stocks/Bonds


Anal cancer disproportionally affects persons living with HIV (PWH), sexual and gender minorities, and those with gynecologic cancers, condyloma acuminata, and solid organ transplantation. While expert guidance on anal cancer screening exists for PWH, there are no national guidelines for screening any of these populations. We analyzed clinician characteristics associated with anal cancer screening among providers who care for high-risk populations at an academic medical center including infectious disease (ID) specialists, primary care providers (PCPs), and obstetrician/gynecologists (OBGYNs).We retrospectively reviewed medical charts for patients with HIV, gynecologic cancers, condyloma acuminata, solid organ transplantation, and sexual or gender minority status at Beth Israel Deaconess Medical Center and two affiliated clinics from 01/01/2015 - 08/01/2022. We extracted provider specialties, clinic locations, patient panel demographics, and dates of anal cytology and human papillomavirus (HPV) screening tests. We used chi-squared tests to identify provider factors associated with screening.Of 1,093 providers, at least one anal cytology test was performed by 93.8% (75/80) of ID providers, 55.2% (376/681) of PCPs, 28.3% (41/145) of OBGYNs, and 24.1% (45/187) of other providers (p < 0.001); among screeners, anal HPV co-testing was performed equally across specialties . Providers were more likely to screen if they cared for PWH , majority cis-men , or majority publicly insured patients . Providers were less likely to screen if they cared for majority cis-women  or majority privately insured patients . Screening practices did not differ by the racial composition of providers’ patient panels (p=.21).While many ID specialists performed anal cancer screenings, other providers were less likely to screen. Providers caring for many PWH, cis-men, or publicly insured patients were more likely to screen. Additional research is needed to clarify screening guidance and optimize screening practices for all higher-risk populations, especially non-PWH groups.Douglas Krakower, MD, Gilead: Grant/Research Support|Merck: Grant/Research Support|U. North Texas Health Sciences Center: Funding for mentoring|UAB: Advisor/Consultant|UpToDate, Inc.: Royalties|Virology Education: Honoraria


Streptococcus pneumoniae (SPN). This study evaluated the in vitro antimicrobial activity of BPR and comparator agents against recent SPN isolates causing lower respiratory tract infections in patients at medical centers in the United States (US).Ceftobiprole (BPR) is an advanced-generation cephalosporin approved in Europe and many non-European countries for the treatment of community-acquired pneumonia and non–ventilator-associated hospital-acquired pneumonia in adults caused by indicated species, including A total of 2,793 SPN isolates from 32 US medical centers (2016–2020) were collected from patients with lower respiratory tract infections. Isolates were tested for antimicrobial susceptibility using the Clinical and Laboratory Standards Institute (CLSI) broth microdilution method. MIC interpretations for BPR and comparators utilized European Committee on Antimicrobial Susceptibility Testing (EUCAST) or CLSI criteria, respectively. The EUCAST BPR susceptibility breakpoint for SPN was 0.5 mg/L.50/90, 0.015/0.25 mg/L). The MIC50/90 values were stable over all 5 surveillance years. The following comparator agents displayed lower activity against the isolate set: clindamycin (85.5% susceptible [S]), erythromycin (53.2% S), penicillin , tetracycline (79.4% S), and trimethoprim-sulfamethoxazole (72.8% S). BPR maintained excellent in vitro activity against each of the isolate subsets resistant to these comparator antimicrobials . This SPN isolate set was also 99.4% S to levofloxacin, 97.4% S to ceftriaxone (using non-meningitis breakpoints), and 100% S to linezolid and vancomycin.BPR inhibited 99.5% of all SPN isolates at the EUCAST breakpoint . These data indicate that BPR merits further investigation as a potential option for the treatment of lower respiratory tract infections caused by SPN in the US.BPR exhibited potent Leonard R. Duncan, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|CorMedix: Grant/Research Support|Melinta: Grant/Research Support|Pfizer: Grant/Research Support Mariana Castanheira, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|bioMerieux: Grant/Research Support|Cipla: Grant/Research Support|CorMedix: Grant/Research Support|Entasis: Grant/Research Support|Melinta: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support Jennifer Smart, PhD, Basilea Pharmaceutica International Ltd, Allschwil, Switzerland: Stocks/Bonds Mark E. Jones, PhD, Astellas Pharma Global Development, Inc: Support for the present publication|Basilea Pharmaceutica International Ltd: Employee of Basilea Pharmaceutica International Ltd|Basilea Pharmaceutica International Ltd: Stocks/Bonds Rodrigo E. Mendes, PhD, AbbVie: Grant/Research Support|Basilea: Grant/Research Support|Cipla: Grant/Research Support|Entasis: Grant/Research Support|GSK: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support|Shionogi: Grant/Research Support


The beta variant drove broad immunity against other SARS-CoV-2 variants, including omicron. We developed 2 vaccines targeting the beta variant receptor-binding domain (RBD): a recombinant dimeric RBD-human IgGth dose of either an adjuvanted  protein vaccine , or mRNA vaccine , or placebo  at least 90 days after 3rdboost or prior COVID infection . All participants received one dose of study vaccine or placebo on Day 1, in double-blind manner. Bleeds occurred on days 1 (prior to vaccination), 8, 29, 90 and 180, and safety monitoring was conducted for 180d. An external comparison group of healthy adults who received a 4th dose booster of a licensed bivalent mRNA COVID vaccine were evaluated for immunogenicity. ClinicalTrials.gov NCT05272605.76 healthy adults aged 18–64y, previously vaccinated with 3 doses of licensed SARS-CoV-2 vaccines, were randomised to receive a 4Figure 1Trial profileNo vaccine-related serious or medically-attended AEs occurred. Protein vaccine reactogenicity profile was mild (no Grade-3). The mRNA was slightly more reactogenic at higher dose levels. Optimal anti-RBD antibody responses were recorded for the 45µg dose of protein vaccine and for 50µg of mRNA vaccine, but titre fold rise (GMFR) was stronger for the lower mRNA dose . A similar pattern was seen with live virus neutralisation and surrogate & pseudovirus neutralisation, including against BQ.1.1 and XBB.1.5 subvariants . Binding antibody titres were stronger for both study vaccines compared to those from a licensed bivalent mRNA COVID vaccine . T-cell studies showed a balanced Th1-Th2 profile, with CD4 & CD8 activation by both vaccines, stronger for CD8 with the mRNA vaccine.Fig 2.Pre- (Day 1) and Post-booster (Day 29) Immunogenicity: Binding antibody (ELISA) and Microneutralisation.Fig 3.Booster seroresponses: Geometric mean fold rises (GMFR) by vaccine type and dose, surrogate virus neutralisation (sVNT).Both protein and mRNA beta RBD vaccines showed strong immune boosting against beta, ancestral and omicron strains, and was similar to that of a licensed bivalent mRNA COVID vaccine. There were no safety concerns and the reactogenicity profile was mild.Terry Nolan, MD, PhD, Clover: Board Member|CSL Seqirus: Advisor/Consultant|CSL Seqirus: Grant/Research Support|Dynavax: Grant/Research Support|GSK: Advisor/Consultant|GSK: Board Member|GSK: Grant/Research Support|Iliad: Grant/Research Support|Moderna: Advisor/Consultant|Moderna: Grant/Research Support|MSD: Advisor/Consultant|MSD: Grant/Research Support|Novavax: Board Member|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support|SK Bio: Board Member Sharon Lewin, MBBS PhD, Abbvi: Advisor/Consultant|Esfam: Advisor/Consultant|Gilead: Advisor/Consultant|Gilead: Honoraria|MSD: Honoraria|Vaxxinity: Advisor/Consultant|VIIV: Advisor/Consultant Steven Rockman, PhD, CSL Seqirus: employee|CSL Seqirus: Stocks/Bonds Dale Godfrey, PhD, CSL Seqirus: Grant/Research Support