Population-level longitudinal data evaluating trends in new HIV diagnoses and use of pre-exposure prophylaxis (PrEP) to assess the impact of COVID-19 on HIV prevention efforts are limited. Here, we evaluated changes in new HIV diagnoses in people who could benefit from PrEP (PWBP), PrEP use, and new HIV diagnoses among people prescribed PrEP prior to and during the COVID-19 pandemic in the United States.PWBP prescribed PrEP at least once after January 2012 were identified using a prescription claims database (IQVIA LRxDx). HIV-negative persons who had ever received emtricitabine(F)/tenofovir disoproxil fumarate or F/tenofovir alafenamide for PrEP between July 2019 and December 2022 were included in this analysis. PrEP use was defined as having an active prescription for oral PrEP before supply ended during the month. New HIV diagnoses per 100 persons per month (PPM) was calculated as new diagnoses divided by PWBP with an active enrollment status. Interrupted time series analysis with segmented regression was used to assess changes in the slope of PrEP use and HIV diagnosis before and during the pandemic.Compared to January 2020 (pre-COVID), new HIV diagnoses in PWBP decreased by 44% in April 2020 and 34% in December 2020. New diagnoses subsequently increased each month, reaching pre-COVID levels in July 2021 . PrEP use similarly declined at the start of the pandemic, which was associated with a subsequent increase in new HIV diagnoses among persons in this group . However, PrEP use has increased steadily since November 2020, with a monthly increase of approximately 3600 persons (p< 0.01). As PrEP use increased, we observed a proportional decrease in new HIV diagnoses among people who were prescribed PrEP, with an average of 0.13 new diagnosis per 100 PPM, while new diagnosis in all PWBP increased with an average of 0.60 per 100 PPM during the same post-COVID period.Decreased HIV diagnoses in PWBP early in the pandemic coincided with stay-at-home restrictions and peaks in COVID-19 hospitalizations, which may have influenced sexual behaviors and HIV testing access. The decrease in PrEP use and subsequent increase in HIV diagnoses highlight the importance of sustained access to PrEP and other HIV prevention services during public health emergencies.Li Tao, MD, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds J Carlo Hojilla, RN, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Valentina Shvachko, MS, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Juan Yang, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Christoph C. Carter, MD, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Moupali Das, MD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds Melanie de Boer, PhD, Gilead Sciences, Inc: Employee|Gilead Sciences, Inc: Stocks/Bonds


Escherichia coli (UPEC) accounting for 80% of cases. With recent transitions in healthcare toward virtual visits, data on multi-drug resistance (MDR) (resistant to ≥3 antibiotic classes) by care setting are needed to inform empiric treatment decision-making.Urinary tract infections (UTIs) cause significant disease and economic burden. Uncomplicated UTIs (uUTIs) occur in otherwise healthy individuals without underlying structural abnormalities, with uropathogenic We evaluated UPEC resistance over time and by care setting , in adults who received outpatient care for uUTI at Kaiser Permanente Southern California between January 2016 and December 2021.Figure 1) both in virtual and in-person settings (p-for trend < 0.001). Resistance to penicillins overall (29%), co-resistance to penicillins and trimethoprim-sulfamethoxazole (TMP-SMX) (12%), and MDR involving penicillins and TMP-SMX plus ≥1 antibiotic class were common (10%) . Resistance to 1, 2, 3, and 4 antibiotic classes was found in 19%, 18%, 8%, and 4% of isolates, respectively; 1% were resistant to ≥5 antibiotic classes, and 50% were resistant to none. Similar resistance patterns were observed over time, and by care setting.We included 174,185 individuals who had ≥1 UPEC uUTI , who were 92% female, and 46% Hispanic with a mean age 52 years (standard deviation 20). Overall, UPEC MDR decreased during the study period (13 to 12%) (We observed a slight decrease in both class-specific AMR and MDR of UPEC overall, most commonly involving penicillins and TMP-SMX, and consistent over time and by care setting. Virtual healthcare may expand access to UTI care without increased risk for MDR and the need for setting-specific antibiograms.Jennifer H. Ku, PhD MPH, GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Katia J. Bruxvoort, PhD, MPH, Dynavax: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support Sara Y. Tartof, PhD MPH, Genentech: Grant/Research Support|GSK: Grant/Research Support|Pfizer: Grant/Research Support|SPERO: Grant/Research Support


Patients with HIV who adhere to antiretroviral (ARV) therapy can achieve and maintain viral suppression (defined as < 200 copies of HIV/mL). Integrated Health System Specialty Pharmacies (HSSPs) help patients overcome barriers to ARV adherence, but there are limited data on the impact of HSSPs on clinical outcomes. This study compared viral suppression for patients filling ARVs at UMass Memorial Specialty Pharmacy to those utilizing a non-integrated specialty pharmacy (non-HSSP).In this retrospective cohort study, patients aged ≥18 years with an HIV diagnosis, encounter at the UMass Memorial Medical HIV Clinic, an ARV medication order, and at least one viral load (VL) result between January 2018 and May 2022 were identified from the medical record. Data included: age, sex, race, ethnicity, comorbidities, and all VL results over the study period. Time of first HSSP fill date was used to identify patient start in the respective pharmacy. VL results were divided into time under HSSP or non-HSSP . The index time was first VL for patients in either the HSSP or non-HSSP group.To account for multiple VL measures per patient, a Generalized Estimating Equation logistic regression estimated odds ratios (OR) and a 95% confidence interval. An OR >1 indicates greater viral suppression.Viral load (VL) lab results were collected while patients were in Integrated Health System Specialty Pharmacies (HSSP) or Non-Integrated Specialty Pharmacy (Non-HSSP). Index time (time=0) is firts VL result while in HSSP or Non-HSSP. Examples of 3 patients timelines, each represents a lab result.Of the 889 patients identified, 326 provided VL results under HSSP while 681 contributed results for non-HSSP; 118 patients provided results for both groups . Of the 5,295 VL results, 2,028 were from HSSP patients and 3,267 from the non-HSSP group. Of the 5,295 total VLs, 90.6% indicated viral suppression, with the average rate of 91.0% in the HSSP group vs 86.0% in the non-HSSP group. Table 1 displays unadjusted and adjusted ORs estimates. The HSSP group had a higher rate of viral suppression . Sex, ethnicity, and race were not significantly associated with viral suppression, which decreased with Charlson Comorbidity Index (CCI) 1-3; increased with age; and increased over time (from index date of VL).Among patients evaluated at UMass Memorial HIV Clinic, those filling ARV medications at the HSSP demonstrated higher rates of viral suppression compared to patients utilizing a non-HSSP.Karen I. Salomon-Escoto, MD, Novartis: clinical trial PI Jonathan Kay, MD, Aker BioMarine AS: Grant/Research Support|Alvotech Swiss AG: Advisor/Consultant|Boehringer Ingelheim GmbH: Advisor/Consultant|Bristol Myers Squibb Co.: Advisor/Consultant|Fresenius Kabi: Advisor/Consultant|Galapagos NV: Grant/Research Support|Inmagene LLC: Independent Data Monitoring Committee member|Kolon TissueGene, Inc.: Independent Data Monitoring Committee member|Novartis Pharmaceuticals Corp.: Advisor/Consultant|Organon LLC: Advisor/Consultant|Pfizer Inc.: Advisor/Consultant|Samsung Bioepis: Advisor/Consultant|Sandoz Inc.: Advisor/Consultant|Scipher Medicine: Advisor/Consultant|Teijin Pharma Ltd.: Advisor/Consultant|Wolters Kluwer NV: Royalties for UpToDate


Individuals with immunocompromising conditions are at high risk of severe disease from COVID-19. The objectives of this study were to describe the clinical features, risk factors, and outcomes of COVID-19 in immunocompromised (IC) adults hospitalized with acute respiratory infection (ARI).We enrolled patients ≥ 18 years of age hospitalized with ARI at two Emory University hospitals from May 2021 – Aug 2022. Patient interviews and medical abstractions were completed. Nasopharyngeal and oropharyngeal swabs were tested for SARS-CoV-2 using BioFire Respiratory Panel, and results of standard-of-care testing were recorded. IC was defined using comorbidities from the medical chart . Primary vaccination consisted of 3 mRNA or 1 J&J + 1 other dose for IC patients, and 2 mRNA or 1 J&J for non-IC patients. Vaccine effectiveness (VE) was calculated using a test-negative case-control design. Multivariable logistic regression with stepwise selection yielded a final model controlling for employment, past COVID-19, and blood disorders using SAS v9.4.Of 1677 enrolled participants, 1653 had SARS-CoV-2 testing, of whom 850 (50.7%) were positive and 231 (27.2% of 850) were IC. Compared to non-IC patients with SARS-CoV-2, IC patients were significantly older ), male (57.1%), and had underlying comorbidities, including blood disorders (13.9%) and chronic kidney disease (36.8%). IC patients were more commonly infected with the Omicron variant, while non-IC patients were more commonly infected with Alpha or Delta. Compared to non-IC, IC patients had longer hospitalization duration , required positive-pressure ventilation (CPAP/BiPAP) (13.9%), and died (6.5%). IC patients had less commonly received a full COVID-19 vaccine series (19.9% vs. 25.8%) and adjusted VE of primary COVID-19 vaccine series against hospitalization for ARI was lower in the IC ) vs. non-IC patients ).Compared to non-IC hospitalized adults, COVID-19 VE against hospitalization for ARI was lower in IC patients, who were more likely to experience severe outcomes and death.Laura A. Puzniak, PhD. MPH, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Robin Hubler, MS, 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 Timothy L. Wiemken, PhD, Pfizer Inc: Employee|Pfizer Inc: Stocks/Bonds Benjamin Lopman, PhD, Epidemiological Research and Methods, LLC: Advisor/Consultant|Hillevax, Inc: Advisor/Consultant Nadine Rouphael, MD, Icon, EMMES, Sanofi, Seqirus, Moderna: 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


COVID-19 vaccine preferences can influence vaccine coverage. Discrete choice experiments (DCE) can be used to elicit people’s trade-offs. DCEs require evidence-based attribute selection and validation of understanding with lay audiences. To inform a future DCE, a pre-test was conducted to examine the survey and refine six attributes selected from a targeted literature review and expert interviews.Interviews were conducted in March 2023 in Canada, Germany, the UK, and US. Self-reported anti-vaccinationists were excluded. Eligible individuals were interviewed during the completion of a survey that included 11 choice tasks and supplementary questions. The “think aloud” method was used to evaluate participants’ understanding of the survey and if they were making trade-offs as hypothesized. Four country-level experts validated the survey modifications based on the results.Six phone interviews were completed in each country (N=24). Mean age was 43.7; 50% were women; 50% reported receiving the full COVID-19 vaccine series; 45.8% received the initial series but were unsure about additional doses; 1 was unvaccinated (4.2%).Participants’ top four priorities were vaccine protection against COVID-19, serious side-effects, protection against severe COVID-19, and common side-effects, followed by vaccine type and timing of COVID-19/influenza vaccines .More than half of the participants would consider co-administration of COVID-19 and influenza vaccines, either as two separate injections (58.3%) or as a single, combined injection (62.5%) . Most individuals (54.2%) preferred an annual COVID-19 vaccine; over every 6 months (4.2%), and 20.8% were indifferent .When deciding to get vaccinated, most considered the following to be important: how long a vaccine was examined in humans (65.2%), how long a vaccine was used in a vaccination program (62.5%); 50% considered vaccine type (mRNA or protein subunit) important .This study validated the importance of key vaccine attributes driving people’s choices and feedback was used to improve the clarity of attribute descriptions. A future DCE will be fielded to increase the understanding of COVID-19 vaccine preference and hesitancy.Sumitra Sri Bhashyam, MSc, PhD, Novavax Inc: Grant/Research Support L.G Shane, Pharm.D., RPH., BScPharm., Novavax Inc: Employee of Novavax Inc|Novavax Inc: Stocks/Bonds Hannah B. Lewis, MSc, PhD, Novavax Inc: Grant/Research Support Marie de la Cruz, MS, Novavax Inc: Grant/Research Support Jayne Galinsky, PhD, Novavax Inc: Grant/Research Support Keeva Demchuk, n/a, Novavax Inc: Grant/Research Support Nancy M. Waite, Waite PharmD FCCP, GSK: Advisor/Consultant|Novavax Inc: Honoraria|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant|Sanofi: Grant/Research Support Jeffrey V. Lazarus, PhD, MIH, MA, AbbVie: Advisor/Consultant|AbbVie: Conference travel|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Moderna: Honoraria|Novavax Inc: Advisor/Consultant|Novavax Inc: Honoraria|Novo Nordisk: Honoraria|Roche Diagnostics: Grant/Research Support David M. Salisbury, CB FMedSci FRCP FRCPCH FFPH, Clover Pharmaceuticals: Advisor/Consultant|GSK: Advisor/Consultant|Moderna: Advisor/Consultant|Novavax Inc: Honoraria|Sanofi: Advisor/Consultant


C. difficile toxin production or toxin gene presence. In two phase 3 trials with varied diagnostic testing methods, dosing with fecal microbiota spores, live-brpk  was associated with low rCDI rate ≤8 wks . In ECOSPOR IV, recurrence rates with FMS ≤8 wks were similar by diagnostic method . We evaluated (post hoc) if pt microbiome profiles differed by diagnostic method at study entry.rCDI is characterized by diarrhea reemergence after symptom resolution on standard-of-care antibiotics and positive test for a) ECOSPOR III, a placebo-controlled trial in pts with ≥2 prior rCDI episodes and diagnosis by toxin EIA (TOX+) and b) ECOSPOR IV, an open-label trial in pts with ≥1 prior rCDI and diagnosis by TOX+ with/without PCR or PCR+. Pts had ≥3 unformed stools/day for 2 consecutive days and symptom resolution on antibiotics before enrolling. Samples were analyzed for alpha diversity and engraftment of dose species not present at baseline using whole metagenomic sequencing. Concentrations of primary bile acids (1°BA), which cause C. difficile spore germination, were measured by targeted LC–MS panel. Statistical analyses in FMS-treated pts compared Shannon diversity, engraftment, and 1°BA concentration changes from paired baseline–Week 1 samples between subgroups.Baseline (pre-dose) stool samples were obtained from pts in P>0.05); engraftment magnitude after FMS was comparable across trials (P>0.05) . Baseline 1°BA concentrations were comparable across trials (P>0.05) and subgroups (P>0.05) and decreased by Week 1 after FMS in TOX+ (P< 0.001) and PCR+ (P< 0.001) subgroups .Baseline Shannon diversity was similarly low across TOX+ and PCR+ subgroups (Regardless of diagnostic method, microbiota diversity appeared similarly disrupted at baseline and improved rapidly by 1 wk after FMS. Engraftment magnitude and 1°BA concentration changes appeared similar across diagnostic subgroups. These data further support the low recurrence rates shown in trials of FMS.Anne J. Gonzales-Luna, PharmD, BCIDP, Cidara Therapeutics: Grant/Research Support|Ferring Pharmaceuticals: Personal Fees|Paratek Pharmaceuticals: Grant/Research Support|Seres Therapeutics: Grant/Research Support Kevin Litcofsky, PhD, Seres Therapeutics: inventor on patents assigned to Seres Therapeutics|Seres Therapeutics: Employment|Seres Therapeutics: Stocks/Bonds Tim Straub, MS, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Dina Hot, PhD, Aimmune Therapeutics: Employee Barbara McGovern, MD, Seres Therapeutics: Stocks/Bonds Brooke Hasson, PhD, Sage Therapeutics: Stocks/Bonds|Seres Therapeutics: Stocks/Bonds Matthew Sims, MD, PhD, Adaptive Phage Therapeutics: Grant/Research Support|Applied Biocode: Advisor/Consultant|Biotest AG: Grant/Research Support|ContraFect: Grant/Research Support|Finch: Grant/Research Support|Janssen: Grant/Research Support|Leonard-Meron Biosciences: Grant/Research Support|Merck and Co: Grant/Research Support|Novozyme: Grant/Research Support|OpGen: Advisor/Consultant|OpGen: Grant/Research Support|Pfizer: Grant/Research Support|Prenosis: Advisor/Consultant|Prenosis: Grant/Research Support|QIAGEN: Grant/Research Support|Seres: Grant/Research Support|Summit Therapeutics: Grant/Research Support Christopher Ford, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds Matthew Henn, PhD, Seres Therapeutics: Employee|Seres Therapeutics: Stocks/Bonds


Candida infections in acute care hospitals, it is critical to understand the epidemiology of healthcare-associated acquisition of these fungal pathogens. Electronic health record (EHR) data is an underutilized resource in identifying potential transmission in this setting.Given increasing resistance and incidence of Candida glabrata ( >48 hrs after admission) between 1/1/2018 and 2/29/2020. Patient location in the hospital and documented contacts between patients and healthcare personnel (HCP) were extracted from the hospital EHR system. Documented contact by a HCP with 2 different patients within 6 hours was considered a potential connection between patients. Prior room occupancy within 7 days was considered potential environmental source. Similarity of C. glabrata infection was determined by isolate antifungal susceptibility profiling where minimum inhibitory concentration (MIC) to fluconazole and micafungin had to be within one doubling dilution difference.Retrospective analysis of potential source of hospital-onset infections (HOI) with C. glabrata infections were identified, of which 104, were considered HOIs. Of the 104 HOIs, 16 (15%) were associated with HCP connections, though 3 (3%) were also associated with prior room occupants. Four of the isolates matched exactly, while 7 had the same patterns of resistance and the MICs of fluconazole were within a single doubling dilution while micafungin was the same. One of the latter isolates was resistant to fluconazole. The mean time between HCP-associated infections was 11 days and the mean number of connections was 25.A total of 156 Time-line of Candida glabrata infections and HCP-associated connectionsTop panel and lower panel are part of the same timeline but split into two panels for visualization. Dots denote collection date of C. glabrata isolates. Larger grey dots are isolates from potential source patients  while black larger dots are the target patients. In two cases there was suspected onward transmission from a secondary infection, denoted by the larger blue dots. Arrows denote the associated transmission. Highlighted dots denote community vs. hospital-onset primary infections.C. glabrata leading to HOI is a rare event; however, HCP-mediated transmission was the main source of identified potential transmission events rather than direct environmental contamination. While antimicrobial stewardship, early identification, and prevention interventions should continue to be prioritized in Candida prevention programs, EHR data can be helpful in identifying potential transmission events. Further studies are needed to evaluate C. glabrata colonization pathways, as well as other Candida spp., such as C. auris, which may have different transmission characteristics.Transmission of Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Sean Zhang, MD, PhD, Applied BioCode: Grant/Research Support|IMMY Diagnostics: Grant/Research Support|KARIUS: Advisor/Consultant|Pearl Diagnostics: Grant/Research Support|Scanogen: Grant/Research Support|T2 biosystems: Advisor/Consultant|Vela Diagnostics: Grant/Research Support


Correction to: Japanese Journal of Radiology (2023) 10.1007/s11604-023-01400-7In the original publication, part b in caption of Fig. 5 should read as:Sagittal T1WI shows hyperintensity anteriorly and mildly hypointensity posteriorly.Reference 2 should read as:WHO Classification of Tumours Editorial Board. Endocrine and Neuroendocrine tumours [Internet].https://tumourclassification.iarc.who.int/chapters/53.Lyon (France): International Agency for Research on Cancer; 2022 [cited 2022 Nov 1]. . The original publication has been corrected.


Once-daily oral tenofovir-based combinations as pre-exposure prophylaxis (PrEP) are effective biomedical HIV prevention strategies. Still, low adherence and/or persistence can lead to decreased efficacy. This study describes the characteristics and HIV incidence in commercially-insured US oral PrEP users. Usage pattern results were previously presented.This retrospective study used IQVIA™ PharMetrics Plus data (1/1/2015–3/31/2020) to identify adults newly initiated (index date) on emtricitabine/tenofovir disoproxil fumarate (FTC/TDF) as daily PrEP. Users had ≥ 6 months (mos.) of continuous enrollment pre-index (baseline); those diagnosed with HIV or with antiretroviral therapy (ART) use during baseline were excluded. User characteristics were described during the baseline period. Users with both an HIV diagnosis and ART dispensing post-index were considered to have acquired HIV. A sensitivity analysis was conducted using ≥ 2 dispensings of ART on separate days to define HIV infection, regardless of documented HIV diagnosis. Time to HIV infection from the index date and from the latest PrEP dispensing was reported. A separate analysis without ≥ 6 mos. of continuous enrollment pre-index was performed.Table 1). Mean [median] length of follow-up was 504 [390] days. By 3 mos. after initiation, 0.3% of FTC/TDF users had acquired HIV, which increased to 0.5% by 12 mos. (Table 2). The mean [median] time to detected HIV infection from index was 235 [95] days, and from the latest PrEP dispensing was 149 [29] days. 60.3% of FTC/TDF users with an HIV diagnosis had PrEP on hand at the time HIV was detected. In the sensitivity analysis requiring only ≥ 2 ART dispensings, rates were slightly higher . In the analysis which removed the 6-month pre-index coverage requirement (Table 3), rates were also higher .In total, 24,232 FTC/TDF users were identified |ViiV Healthcare: Stocks/Bonds Guillaume Germain, MSc, ViiV Healthcare: I am an employee of Analysis Group, a consulting company that received research funds from ViiV Healthcare to conduct this study. François Laliberté, MS, GSK: Grant/Research Support Alan Oglesby, MPH, GlaxoSmithKline: Employment|GlaxoSmithKline: Stocks/Bonds Heidi Swygard, MD, ViiV Healthcare: Employee of ViiV Healthcare|ViiV Healthcare: Stocks/Bonds Sean MacKnight, MScPH, ViiV: I am an employee of Analysis Group, a consulting company that received research funds from ViiV to conduct this study. Annalise Hilts, BA, ViiV : Grant/Research Support Mei Sheng Duh, MPH, ScD, Analysis Group, Inc.: Mei Sheng Duh is an employee of Analysis Group, Inc., a consulting company that received funding from GSK to conduct this study|ViiV Healthcare: Grant/Research Support


Herpes zoster (HZ) is characterized by a painful dermatomal rash and is associated with increased healthcare costs. Research quantifying work productivity loss and activity impairment associated with HZ is limited and outdated. This study aimed to describe severity of HZ related pain, health related quality of life, activity impairment, and work productivity among employed adults diagnosed with HZ in the Department of Veterans Affairs (VA) Health System.th Revision (ICD-10) HZ diagnosis were invited to complete an online survey. Respondents were indexed on their HZ diagnosis and included if aged 18-70 years, reported working for pay at index, and had 6 months of baseline continuous enrollment. Respondents were excluded if they had a baseline HZ vaccine, did not complete the survey within 30 days after index, or reported not having HZ or experiencing a rash > 14 days prior to index. Questions used to assess outcomes were based on validated survey instruments (Table 1). Work productivity was described among respondents employed at survey completion. Data were collected from 05/04/2021 to 07/07/2022. Descriptive statistics were used to summarize survey responses.This cross-sectional study utilized a self-reported survey among adults in the VA health system. Eligibility was assessed biweekly from electronic health record data, and adults with an incident International Classification of Diseases, 10Among 231 respondents completing the survey, mean (standard deviation [SD]) age was 49 (10) years and 79% were male. Overall, 70% reported experiencing pain in the last 7 days. Mean (SD)  “average-pain” severity and EQ-5D-3L scores were 4.0 (2.8)  and 0.69 (0.22) , respectively. Mean (SD) activity impairment was 42% (33%). Mean (SD) absenteeism, presenteeism, and overall work impairment were 17% (27%), 35% (30%), and 43% (35%) out of 202, 192, and 202 respondents, respectively.Burden associated with HZ is substantial, with a significant proportion experiencing pain, activity impairment, and work productivity loss. These results provide updated context on the impact of HZ in this population of employed adults in the VA health system.Funding: GlaxoSmithKline Biologicals SA (GSK study identifiers: 208907/HO-16-16967).Shaloo Gupta, MS; ORCID: 0000-0002-2535-2892, Cerner Enviza: Salary|GSK: Funding to employer to conduct and support this study Nai-Chung N. Chang, PhD; ORCID: 0000-0002-4541-8967, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Nikita Stempniewicz, MSc, GSK: Salary|GSK: Ownership Interest Chenchu Bhavani K. Tirupati, MS, MBA, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Gregorio Coronado, MBA, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Kantar Health: Grant/Research Support|Myriad Genetic Laboratories, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Julie A. Lynch, PhD, RN, MBA; ORCID: 0000-0003-0108-2127, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support Cosmina Hogea, PhD; ORCID: 0000-0002-0686-2395, Gilead Sciences: Ownership Interest|GSK: Salary at the time of the submitted work|GSK: Ownership Interest Emily Mulvihill, MBA; ORCID: 0000-0002-1430-8837, Cerner Enviza: Salary|GSK: Funding to employer to conduct and support this study Scott L. DuVall, PhD, Alnylam Pharmaceuticals, Inc.: Grant/Research Support|Astellas Pharma, Inc.: Grant/Research Support|AstraZeneca Pharmaceuticals LP: Grant/Research Support|Biodesix: Grant/Research Support|Celgene Corporation: Grant/Research Support|Cerner Enviza: Grant/Research Support|GSK: Grant/Research Support|Janssen Pharmaceuticals, Inc.: Grant/Research Support|Novartis International AG: Grant/Research Support|Parexel International Corporation: Grant/Research Support


Correction: Systematic Reviews 12, 12 (2023)10.1186/s13643-023-02168-7Following publication of the original article , the autThe incorrect author names are:Oguntade Racheal Tomilola, Ojewole Elizabeth Bolanle and Ogunrombi Modupe OlufunmilayoThe correct author names are:Racheal Tomilola Oguntade, Elizabeth Bolanle Ojewole and Modupe Olufunmilayo OgunrombiThe original article  has been


Venetoclax is a small molecule inhibitor of BCL-2 used in the treatment of acute myelogenous leukemia and chronic lymphocytic leukemia. Recent post-marketing studies on venetoclax suggested that it may predispose to opportunistic infections (OIs). We sought to systematically review the randomized controlled trial (RCT) evidence on venetoclax to assess whether it predisposes patients to infectious adverse events (IAEs) and neutropenia.i.e., a regimen with additional anti-cancer agents) or placebo controls in patients with hematologic malignancies, irrespective of treatment line. Data on IAEs and neutropenia were pooled by Bayesian meta-analysis and we computed the probability of any increased risk in infectious or neutropenic complications (Risk Ratio [RR] >1). Subgroup analyses were conducted based on treatment line, use of an inactive comparator, malignancy type, and prophylaxis strategy. Additionally, we pooled the incidence rates of fatal OIs between venetoclax and comparator arms and compared them by univariate meta-regression.We systematically reviewed the RCTs comparing venetoclax therapy to active . The probabilities of venetoclax increasing the risk of grade 3-5 and fatal IAEs were 86.6%  and 81.1% , respectively. There was a 97.2% likelihood that venetoclax increased the risk of grade 3-5 neutropenia . Venetoclax treatment did not increase the incidence of fatal OIs (P=0.55).Our results suggest that venetoclax likely increases the risk of high-grade neutropenia and IAEs overall, but not fatal OIs. However, our analyses did not identify any specific IAEs that would benefit from routine anti-infective prophylaxis or pre-emptive testing.Michael Sebag, MD, PhD, Amgen: Advisor/Consultant|BMS: Advisor/Consultant|Focus Therapeutics: Advisor/Consultant|Gilead: Advisor/Consultant|Janssen: Advisor/Consultant|Novartis: Advisor/Consultant|Pfizer: Advisor/Consultant|Sanofi: Advisor/Consultant Matthew Cheng, MD, Amplyx Pharmaceuticals: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Honoraria|Cidara Therapeutics: Grant/Research Support|GEn1E lifesciences: Advisor/Consultant|GEn1E lifesciences: Stocks/Bonds|Kanvas Biosciences, Inc.: Board Member|Kanvas Biosciences, Inc.: Pending patents|Kanvas Biosciences, Inc.: Ownership Interest|Merck: Honoraria|nomic bio: Advisor/Consultant|nomic bio: Stocks/Bonds|Pfizer: Honoraria|Scynexis Inc.: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria


Total joint arthroplasty (TJA) is one of the most common surgical operations performed in the US. Periprosthetic joint infection (PJI) is a daunting complication of TJA and is associated with high morbidity. Previous studies have shown that racial disparities exist in postoperative complications of TJAs, including readmissions and mortality. However, it is unclear if such disparities also exist for PJI.A single large hospital system database was used to identify all patients who underwent either primary total knee arthroplasty (TKA) or total hip arthroplasty (THA) between January 2018 and December 2021. Patients were stratified by self-identified racial categories. PJI was defined by ICD-9/10 coding. We present descriptive data as frequencies and percentages for categorical variables and means and standard deviations for continuous variables. We used chi-square tests to estimate crude risk ratios (cRR) and 95% confidence intervals (CIs) for PJI by race.A total of 11,818 patients were included in the final analysis. The majority (96.6%) of patients identified as non-Black (Table 1). The mean age was 69.4 (±10.3) years for non-Black patients and 65.5 (±11.5) years for Black patients. Females represented the majority of non-Black and Black patients who underwent TJA . The majority of TJAs were TKAs for both non-Black and Black patients . The incidence of PJIs was 1.6% among non-Black patients compared to 3.3% among Black patients (cRR (95% CI): 1.99 (1.17 – 3.39); p=0.0112). The majority of PJIs occurred post TKA (Table 1).Preliminary findings suggest that racial disparities exist in PJIs. These findings were not adjusted for possible confounding factors such as age, sex and comorbidities. Future studies are needed to determine if such disparities persist when other factors are considered.Antonia Chen, MD, MBA, Adaptive Phage Therapeutics: Advisor/Consultant|Adaptive Phage Therapeutics: Grant/Research Support|Avanos: Advisor/Consultant|BICMD: Advisor/Consultant|Convatec: Advisor/Consultant|Elute: Grant/Research Support|Ethicon: Advisor/Consultant|GLG: Advisor/Consultant|Guidepoint: Advisor/Consultant|Heraeus: Advisor/Consultant|Hyalex: Stocks/Bonds|IlluminOss: Stocks/Bonds|Irrimax: Advisor/Consultant|Irrimax: Stocks/Bonds|Journal of Bone and Joint Surgery: Deputy Editor|Osteal Therapeutics: Advisor/Consultant|Osteal Therapeutics: Stocks/Bonds|Peptilogics: Advisor/Consultant|Peptilogics: Grant/Research Support|Pfizer: Advisor/Consultant|SLACK Incorporated: royalties|Smith and Nephew: Advisor/Consultant|Sonoran: Stocks/Bonds|Stryker: Advisor/Consultant|Taylor & Francis Group: Royalties|UpToDate: Royalties


The purpose of this study was to monitor the As part of a worldwide surveillance study, a total of 2,942 Gram-negative isolates were collected during 2021 from various infections including IAI, body fluids, respiratory and other sources. Of the 2,942 isolates, 654, 1263, and 1025 were from Asia/Pacific, Europe, and North America, respectively. Minimum inhibitory concentrations (MICs) were determined by CLSI broth microdilution. Antibiotic susceptibility was determined with FDA or CLSI breakpoints.Acinetobacter baumannii or Stenotrophomonas maltophilia, eravacycline exhibited promising activity against these species with MIC50 / MIC90 of 0.5 & 1 and 1 & 2 µg/ml, respectively.Summary MIC data for tested antimicrobials are shown in the Table. Susceptibility to eravacycline for Enterobacterales was 93.9%, 85.7%, 90.0%, and 96.8% for all isolates, MDR Enterobacterales, ESBL-positive, and ESBL-negative isolates, respectively. Although there are no clinical breakpoints for A. baumannii or S. maltophilia, eravacycline demonstrated promising activity against these species. These results suggest that, following several years of clinical use, susceptibility to eravacycline remains high.Eravacycline exhibited sustained high susceptibility against multiple Enterobacterales species, including MDR and ESBL-positive isolates. While breakpoints are not defined for Stephen Hawser, PhD, Allecra: study funding|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Nimmi Kothari, PhD, Allecra: Allecra (study funding)|Innoviva Specialty Therapeutics, Inc.: Honoraria|Roche: Honoraria|Roche: This project has been funded by BARDA (HHSO100201600038C). Federica Monti, PhD, Allecra: Study funded|Innoviva Specialty Therapeutics, Inc.: Honoraria Tony Hodges, MD, La Jolla Pharmaceutical Company: Employee|La Jolla Pharmaceutical Company: Stocks/Bonds Kristie Zappas, PhD, La Jolla Pharmaceutical Company: employee|La Jolla Pharmaceutical Company: Stocks/Bonds


The rationale for a loading dose (LD) prior to administering extended infusion piperacillin/tazobactam (PTZ) is theoretical and based on pharmacokinetic/pharmacodynamic (PK/PD) principles and simulations. The clinical data to support the use of a LD for extended infusion are limited.This is a single-center, retrospective cohort study evaluating adult patients with gram-negative bacteremia who received extended infusion PTZ for at least 48 hours between 2015 and 2022. In December 2019, the study institution developed a policy that automatically ordered a PTZ LD whenever PTZ therapy was prescribed. The study compared patients who received the loading dose to those who did not. Electronic medical records were queried for patient demographic and clinical data. The primary endpoint was 30-day mortality. Key secondary endpoints included clinical cure, time to clinical cure, 14-day mortality, in-hospital mortality, time to mortality, and microbiologic cure. Clinical cure was defined by antibiotic discontinuation or narrowing of antibiotics in the setting of patient survival. Descriptive and inferential statistics were used for all data analyses. Logistic regression modeling was performed to control for confounding.A total of 102 patients were included in the analysis, with 51 patients in the LD group and 51 patients in the no LD group. Baseline characteristics were similar in both treatment groups with the exception of ICU admission which was higher in the LD group . The 30-day mortality was 12% (6/51) in the LD group compared to 6% (3/51) in the no LD group (P = 0.49). There were no significant differences in 14-day mortality, in-hospital mortality, clinical cure, and microbiologic cure. After adjusting for potential confounders, there were no significant associations between LD and 30-day mortality .We observed no significant association between LD for extended infusion PTZ and clinical outcomes. Larger cohorts with adequately powered sample sizes are needed to validate these findings. Future investigations should evaluate the impact of a LD for extended infusion PTZ on safety and PK/PD outcomes.Pinki Bhatt, MD, Sanofi: Grant/Research Support Keith S. Kaye, MD, MPH, Abbvie: Advisor/Consultant|Abbvie: Honoraria|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 Navaneeth Narayanan, PharmD, MPH, BCIDP, Astellas: Honoraria|Beckman Coulter: Honoraria|Merck: Grant/Research Support|Shionogi: Grant/Research Support


S. pneumoniae (SPN) from the USA, as well as the resistance (R) mechanisms in tetracycline (TET) non-susceptible (NS) SPN.Major guidelines recommend β-lactams, macrolides, doxycycline (DOX) or respiratory quinolone monotherapy for outpatients with non-severe community-acquired bacterial pneumonia (CABP). Combination therapy is recommended for outpatients with comorbidities. Omadacycline (OMC) was equivalent to moxifloxacin as monotherapy for adults with CABP and was approved for CABP by the US FDA (2018). The activity of OMC and comparators was evaluated against 1,038 SPN from 31 USA centers (2019-2021) were tested by CLSI broth microdilution. Isolates were from CABP (933), bloodstream infection (72), or nosocomial pneumonia (33). A selection of 119 SPN with DOX MIC of 0.25 - >8 mg/L were subjected to genome sequencing for screening of acquired TET-R genes and target site mutations, and serotyping (ST).tet(M), and TET-NS had low S to DOX (6.6% S) and azithromycin (3.3% S). TET target site mutations were not observed. SPN belonged to 21 ST; 22F and 35B were the most common among TET-S SPN, whereas 15A, 19A, 09N, and 23A were common among TET-NS SPN.Most SPN isolates were susceptible (S) to OMC , levofloxacin  and tigecycline . Other agents had limited activity overall  with decreased S against isolates from certain US regions (Table). Only OMC (100% S), LEV (96.8% S) and TIG (96.7% S) were active against TET-NS  SPN. Cefpodoxime (70.5% S) and amoxicillin-clavulanate (82.0% S) had suboptimal activity against this R subset and other agent had S ≤36.1%. Isolates from the Pacific region tended to be more S than those from other regions. All TET-NS and 1 TET-S  isolates carried tet(M).Options recommended for the empiric treatment of outpatients with CABP show low S against SPN from the US, except against isolates from the Pacific region. Tet(M) remains the dominant R mechanism, which did not affect OMC activity but significantly altered DOX activity. These data suggest that OMC represents a potential empiric option for treating pneumonia caused by SPN in the USA, including against isolates carrying Lalitagauri M. Deshpande, PhD, Melinta: Grant/Research Support|Paratek: Grant/Research Support Michael D. Huband, BS, BARDA: This study has been funded in part by BARDA under Contract No. 75A50120C00001.|Entasis: Grant/Research Support|Paratek: Grant/Research Support|Pfizer: Grant/Research Support Sarah Charbon, MHS, MLS(ASCP)CM, Paratek: 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 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


Enterobacterales (ESBL-E) continues to expand. ESBL-Es commonly colonize the intestinal tract and may propagate the spread of ESBL genes. However, the frequency at which ESBL production occurs in all Enterobacterales (including inducible AmpC-producers) is unknown. This study aims to define the epidemiology of third-generation cephalosporin resistant Enterobacterales (3GC-RE) colonization to understand their burden and contribution to ESBL spread in high-risk populations .The epidemic of extended-spectrum β-lactamase producing Enterobacterales. For inducible AmpC-producing Enterobacterales, cefepime +/- clavulanic acid disk test was performed. Carbapenem-resistant Enterobacterales (CRE) were tested for carbapenemase-production using the modified carbapenem inactivation method (mCIM) and by the CARBA 5 lateral flow assay, if mCIM positive.Surveillance cultures for 3GC-RE were performed by collecting perirectal swabs among high-risk populations at The Johns Hopkins Hospital. Isolates were identified by MALDI-TOF MS after recovery on 3GC selective chromogenic media. Antimicrobial susceptibility testing was performed using lyophilized broth microdilution panels following Clinical and Laboratory Standards Institute (CLSI) guidelines. 3GC-RE were characterized using the CLSI ESBL disk test among recommended Escherichia coli, Klebsiella pneumoniae and K. oxytoca being the most common ESBL-E. Additionally, 14 (12%) were CRE with K. pneumoniae, E. coli and Enterobacter cloacae complex being the most common CRE. Of CRE, 7 (50%) were carbapenemase producers with 4 (57%) KPC, 2 (29%) NDM and 1 (14%) KPC and NDM.Of 966 surveillance cultures, 99 (10%) were positive for 3GC-RE and 14 (1%) were positive for CRE. Almost all 112 (99%) rectal swabs had a single organism isolated while multiple organisms were isolated from 1 (1%). 114 bacterial isolates were recovered (Table 1). Of the 3GC-RE, 66 (58%) were ESBL-producers with Enterobacterales.Colonization with 3GC-RE and CRE occurs in 10% and 1% of rectal swabs collected from high-risk patients, respectively. 58% of 3GC-RE were ESBL producers and ranged between 0-100% among 3GC-RE; including up to 33% from inducible AmpC producing Sara E. Cosgrove, MD, MS, Debiopharm: Advisor/Consultant|Duke Clinical Research Institute: Advisor/Consultant Patricia J. Simner, PhD, Affinity Biosensors: Grant/Research Support|BD Diagnostics: Advisor/Consultant|BD Diagnostics: Grant/Research Support|Entasis: Advisor/Consultant|GeneCapture: Stocks/Bonds|Merck: Advisor/Consultant|OpGen Inc: Board Member|OpGen Inc: Grant/Research Support|OpGen Inc: Honoraria|Qiagen Sciences Inc: Advisor/Consultant|Qiagen Sciences Inc: Grant/Research Support|Shionogi Inc: Advisor/Consultant|T2 Biosystems: Grant/Research Support


We compared the performance of BIOFIRETotal of 250 leftover NPS  obtained from children as a part of routine diagnostic care and tested previously by standard of care assay were enrolled in the study and tested on all three respiratory panel multiplex platforms. Results for Flu A, Flu B and SARS CoV-2 were compared to a composite reference standard (consensus positive = positive result in ≥2 assays and consensus negative = negative result in ≥2 assays) to calculate positive percent agreement (PPA) and negative percent agreement (NPA). For RSV, PPA and NPA were calculated by comparing Xpert and SPOTFIRE assays only. Discrepant samples were tested by CDC single plex PCR for each of the viruses.PPA and NPA for all targets is shown in Table 1. PPA for Flu A and Flu B were similar across all platforms and NPA >95% by all assays. PPA and NPA for RSV between Xpert and SPOTFIRE was 98% and 92% respectively. CDC PCR assays performed on samples with discrepant results confirmed 3/13 Flu A, 24/33 SARS-CoV-2 and 9/15 RSV detections with 50% samples being missed with CT < 35. SPOTFIRE can detect 15 respiratory pathogens (including viruses and bacteria) and was positive for a virus in 220/250 (88%) samples. Additional viral targets  were detected either as single or co-detections . All samples with initial invalid results on Xpert , SPOTFIRE  and Cobas  were valid on re-testing. Total hands-on time  ranged between 1.13 minutes to 2.34 minutes for all assays.Table 1.Performance characteristics of SPOTFIRE Respiratory/Sore Throat (R/ST) Panel, Xpert® Xpress SARS-CoV-2/Flu/RSV assay and Cobas® SARS-CoV-2 & Influenza A/B assay for detection of Flu A, Flu B and SARS-CoV-2 *Samples tested negative for universal Flu A PCRs but positive for Flu A typing PCRs with >37 CT. NA – Not Applicable, TP – True positive, TN – True Negative, FP – False Positive, FN - False NegativeFigure 1.Detections of other respiratory viruses  on the SPOTFIRE platformAll 3 assays showed comparable performance ( >95% agreement) for Flu A and B detection; performance for SARS-CoV-2 and RSV detection varied, even for samples with high viral load. SPOTFIRE provides the advantage of detecting many respiratory pathogens. Overall, the assays were easy to perform with minimum technical skill.Rangaraj Selvarangan, BVSc, PhD, D(ABMM), 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


LET is a CMV DNA terminase complex inhibitor approved for prophylaxis of CMV infection and disease in adult CMV-seropositive allogeneic HCT recipients. This study evaluated PK, safety and efficacy of LET for CMV prophylaxis in pediatric allogeneic HCT recipients.This was a Phase 2b, single-arm, multicenter, open-label study (NCT03940586). Participants (pts) from birth to < 18 years (y) were sequentially enrolled in 3 age groups (AG): AG1, 12 to < 18 y; AG2, 2 to < 12 y; AG3 < 2 y. All pts received LET orally (PO) or intravenously (IV) with/without cyclosporin A (CsA). Pediatric target exposures were based on model-predicted Phase 3 population simulations for adult HCT recipients, ranging from 16,900 ng.h/mL  to 147,800 ng.h/mL . PK parameters were determined by non-compartmental analysis . Safety was assessed by evaluation of adverse events.Of 63 pts administered LET, the majority were White (69.8%) and male (69.8%); median age of 11 (0–17) y; median weight of 32.4 (5.1–95.0) kg.PK : AG1  achieved exposures within safety margins of adult HCT pts. AG2 : 14 pts  who received LET alone achieved target range exposures; 2 pts who received IV LET with CsA had exposures slightly lower than target range. AG3 : 3 pts who received LET with CsA achieved exposures trending lower than median target. Therefore, LET dose was increased for 5 pts (< 10 kg and aged < 2 y) to achieve target range exposures.Safety (n=63): LET was well-tolerated with a safety profile similar to that observed in adults.Efficacy (n=56): The proportion of pts with clinically significant CMV infection (CMV disease/pre-emptive treatment for CMV viremia) through Week 24 post-HCT was similar (25%) to that seen in adults receiving LET in the Phase 3 study (37.5%).LET administration for CMV prophylaxis in pediatric HCT recipients at doses used in this study resulted in exposures within development program safety margins and was associated with similar safety and efficacy when compared with LET use in adult HCT recipients.Johannes H. Schulte, MD, The German Cancer Consortium (DKTK): Grant/Research Support Andreas H. Groll, MD, Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Astellas: sered at the speakers’ bureau|Basilea: Advisor/Consultant|Basilea: served at the speakers’ bureau|F2G: Advisor/Consultant|F2G: served at the speakers’ bureau|Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: served at the speakers’ bureau|Merck Sharp & Dohme LLC: Advisor/Consultant|Merck Sharp & Dohme LLC: Grant/Research Support|Merck Sharp & Dohme LLC: served at the speakers’ bureau|Pfizer: Advisor/Consultant|Pfizer: Grant/Research Support|Pfizer: served at the speakers’ bureau Valerie L. Teal, MS, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Barbara A. Haber, MD, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Christopher L. Gilbert, n/a, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Jacqueline B. McCrea, PharmD, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Mayankbhai Patel, PhD, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Karsten Menzel, PhD, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds Cyrus Badshah, MD, PhD, Merck Sharp & Dohme LLC: Wages and Salary made to Author|Merck Sharp & Dohme LLC: Stocks/Bonds


Antimicrobial resistance (AMR) is a growing global concern. Novel antibiotics (ABXs) target resistant pathogens causing gram-negative (GN) bacterial infections. This study assesses the broader impact of novel ABX use on the US healthcare system, including preventing the onward spread of infections and reducing the level of high-threat AMR.A stochastic dynamic transmission model was developed to simulate the interaction between infection transmissibility, bacterial resistance development, and multiple lines of ABX. Included infection types were intra-abdominal infections, urinary tract infections and hospital-acquired /ventilator-associated pneumonia. Included AMR types were carbapenem-resistant and ESBL-producing enterobacterales (CRE and ESBLE), and multi-drug resistant pseudomonas aeruginosa (MDRP). The model has compartments for non-infected, colonized, or infected patients, with a sensitive or resistant strain in a US hospital. Infected patients receive antibiotics resulting in infection clearance or use of an alternate ABX class. Sensitive pathogens gain resistance due to drug pressure or conversely could lose resistance. Ordinary differential equations were used to estimate compartment membership. The primary data source was the Premier healthcare database . The model examined the potential reduction in AMR levels and avoided hospital infections, by comparing two scenarios: targeted use of novel ABX for specific AMR types and the status quo with limited novel ABX use.nd or 3rd line of treatment, compared to the status quo, it could result in a ∼1.5% reduction in hospital infections and a change in CRE, ESBLE, and MDRP by −2.5%, −3.6%, and −2.1%, respectively, on an annual basis. The cumulative impact of novel ABXs over 5-10 years was much larger but subject to higher prediction uncertainty. The primary driver of results are infection clearance rates, risk of resistance gain on various ABX, and uptake of novel ABX.When even novel ABXs are reserved as the 2Targeted use of novel ABXs for resistant pathogens could lead to improved, earlier infection clearance with most types of infections and pathogens, thereby reducing infection transmission and rise of high-threat AMR in the long-term.Apoorva Ambavane, PhD, Merck & Co., Inc: Grant/Research Support Michal Litkiewicz, MSc, Merck & Co., Inc: Grant/Research Support Aditya Sardesai, MSc, CSL Seqirus: Advisor/Consultant|Merck & Co. Inc: Grant/Research Support|Merck & Co. Inc: Grant/Research Support Diana Teloian, MA, Merck & Co., Inc: Grant/Research Support Engels N. Obi, PhD, Merck & Co Inc: Employee Joe Yang, PhD, Merck & Co., Inc: Employee|Merck & Co., Inc: Stocks/Bonds


SARS-CoV-2 viral dynamics offer insights into clinical trajectories and immune responses. While research has explored SARS-CoV-2 viral kinetics by variant and immune status, changes in population immunity make results difficult to interpret. Here, we examined SARS-CoV-2 viral kinetics in a community-based cohort of immunologically naïve adults.Unvaccinated adults 30 to 64 years of age without prior infection were followed for ≤ 72 weeks. Subjects submitted weekly nasal swabs for SARS-CoV-2 RT-PCR; if symptomatic or positive, swabs were collected every other day (up to 14 days). We examined RT-PCR cycle threshold (Ct) results from infections with sufficient data, defined as ≥ 3 swabs collected between ‒10 and 28 days of the peak Ct value with ≥ 1 Ct< 30. Bayesian hierarchical piecewise models were used to estimate viral kinetics by variant (classified by date) or first vs. second infections using data from peak swabs and those collected within ±3 days of another swab; if negative, Ct values were set to the detection limit and only the first of consecutive negatives were included.Sufficient data were available for 179/187 (96%) first SARS-CoV-2 infections, with 27 (15%) Delta, 132 (74%) Omicron BA.1/BA.2, and 20 (11%) Omicron BA.4/BA.5 infections. Of these, 35 (20%) subjects had a second infection while unvaccinated (32 [91%] sufficient data). Figure 1 shows Ct values and model predictions by variant or infection status. Lower mean peak Ct values were found for first vs. second infections , and suggested for Delta vs. Omicron BA.1/BA.2 infections . Delta had a shorter mean time to peak  and longer clearance  vs. Omicron BA.1/BA.2 infections; first infections had longer clearance  vs. second infections.Modeled estimates suggest Delta infections experienced higher viral loads, shorter time to peak, and longer clearance times compared with Omicron BA.1/BA.2. First infections had higher viral loads and longer clearance times vs. second infections. As population immunity is dynamic, characterizing viral kinetics among immunologically naïve individuals is valuable to inform SARS-CoV-2 trajectories.Jim Boonyaratanakornkit, MD, PhD, AstraZeneca: Advisor/Consultant|GlaxoSmithKline: Grant/Research Support|IgM Biosciences: Grant/Research Support|IgM Biosciences: Patent on antibodies to respiratory viruses|Vir Biotechnology: Grant/Research Support Michael J. Boeckh, MD PhD, Allovir: Advisor/Consultant|Amazon: Grant/Research Support|Ansun: Grant/Research Support|Merck: Advisor/Consultant|Merck: Grant/Research Support|Moderna: Advisor/Consultant|Symbio: Advisor/Consultant Alpana Waghmare, MD, Allovir: Grant/Research Support|Amazon: Grant/Research Support|Ansun Biopharma: Grant/Research Support|GlaxoSmithKline/Vir: Grant/Research Support|Kyorin Pharmaceuticals: Advisor/Consultant|Pfizer: Grant/Research Support|Vir Biotechnology: Advisor/Consultant


During the 2010–2021 influenza seasons, vaccination coverage was below the 70% target for the United States at 33.4–58.6% among children and 50.2% among adults. The live attenuated influenza vaccine (LAIV) is currently approved for healthcare professional administration (HCPA); however, self- and home-administered LAIVs may provide an additional, effective option for vaccine administration, which could expand seasonal influenza vaccine accessibility. LAIV is a quadrivalent influenza vaccine administered intranasally, with comparable effectiveness to the inactivated influenza vaccine.[3] Broadening vaccine availability to multiple vaccination sites has been shown to increase vaccination rates by up to 22%.[4]Here we summarize the current evidence on self- and home-administered LAIV efficacy and safety, and potential applications for increasing community influenza vaccination accessibility.Publications evaluating the efficacy, safety, and practicality of self- and home-administered LAIV were identified from a literature search with the following search string: (live attenuated influenza vaccine OR LAIV) AND (home administration OR self administration OR self immuni*).Table), home administration was preferred by 64, 74, and 96% of participants. Sample sizes ranged from 41 children to 4561 patients receiving LAIV, with participants aged between 2.6 and 64 years old. A trial of 4561 patients comparing LAIV self- and home administration to HCPA groups found similar effectiveness against influenza-like illness, immunogenicity, and adverse events post-vaccination.In three studies comparing LAIV self- and home administration to HCPA :6337-6343.[3] Bandell A et al. Open Forum Infect Dis. 2020;7(Suppl 1):S709.[4] Ipsos. Expanding flu vaccine access.Ravi Jhaveri, MD, AbbVie: Grant/Research Support|AliOS: Grant/Research Support|AstraZeneca: Advisor/Consultant|Gilead: Grant/Research Support|MedImmune: Advisor/Consultant|Merck: Grant/Research Support|Saol Therapeutics: Advisor/Consultant|Seqirus: Advisor/Consultant Allyn R. Bandell, PharmD, AstraZeneca: employee|AstraZeneca: Stocks/Bonds


The COVID-19 pandemic led to increased respiratory viral testing for patients presenting with acute respiratory infection (ARI). Electronic health record (EHR) data from these visits can be used to assess influenza and COVID-19 vaccine effectiveness (VE). We compared VE data from participating healthcare institutions with VE against medically attended influenza among systematically tested patients actively enrolled in the US Flu VE Network.During the 2021-2022 influenza season, seven sites in the US Flu VE Network identified medically attended episodes of ARI in ambulatory settings based on ICD-10 diagnostic codes and clinical influenza and SARS-CoV-2 testing. Influenza status was determined from the clinical test results. Vaccination status was extracted from the EHR. During the same period, patients with ARI presenting at ambulatory clinics were actively enrolled and tested for influenza. VE and 95% confidence intervals (CI) were estimated comparing the odds of vaccination among influenza-positive versus influenza-negative patients using logistic regression models controlling for age, site, and calendar time.During the 2021-2022 season, 220,162 medical visits for ARI with clinical testing were identified; 2% of tests were influenza positive, 26% were SARS-CoV-2 positive and 73% were negative for both. Overall, 34% of influenza positive and 42% of influenza negative patients had received influenza vaccines; VE using EHR data was 34% [95% CI 29-38]. Among 6,260 enrolled patients, 7% tested positive for influenza, 34% were SARS-CoV-2 positive and 62% were negative for both. Overall, 42% of influenza positive and 59% of influenza negative patients had received influenza vaccines. VE using enrolled patient data was 36% [95% CI 20-49]. VE using EHR data was 35%, 34%, and 6% for patients aged 6 months-17 years, 18-49, and 50+ years versus 40%, 32%, and 10% for enrolled patients.EHR based influenza VE estimates were similar to estimates from the US Flu VE study. Through continued widespread clinical testing, EHR-based platforms may present opportunities to assess VE in sub-groups with insufficient sample size in active surveillance.MaryPatricia Nowalk, PhD, RDN, Merck & Co.: Grant/Research Support|Merck & Co.: Honoraria|Sanofi: Grant/Research Support Emily T. Martin, PhD, MPH, Merck: Grant/Research Support Edward Belongia, MD, Seqirus: Grant/Research Support Carlos G. Grijalva, MD, MPH, AHRQ: Grant/Research Support|CDC: Grant/Research Support|FDA: Grant/Research Support|Merck: Advisor/Consultant|NIH: Grant/Research Support|Syneos Health: Grant/Research Support


Cabotegravir + rilpivirine (CAB+RPV) injections, the first complete long-acting (LA) antiretroviral therapy (ART) regimen, was approved by the FDA in January 2021 for ART-experienced people with HIV (PWH) who are virologically suppressed . We assessed the virologic effectiveness of CAB+RPV LA among ART-experienced individuals with VL < 50 copies/mL at initiation in the first 2 years of use in the OPERA® Cohort, stratified by body mass index (BMI).2).All ART-experienced adults with VL< 50 copies/mL at initiation who received ≥ 1 CAB+RPV LA injection for the first time between 21Jan2021 and 28Feb2023 were followed until 25Mar2023. Individuals on either monthly or every 2-month injection schedules were included. Discontinuation was defined as a regimen switch or 2 consecutive missed injections. VLs were monitored from first injection until CAB+RPV discontinuation, death, or study end. Confirmed virologic failure (CVF) was defined as 2 consecutive VLs ≥ 200 copies/mL or 1 VL ≥ 200 copies/mL followed by discontinuation. Results were stratified by BMI at first injection (< 30 vs. ≥ 30 kg/mAll 1843 PWH who received CAB+RPV injections were ART-experienced at start and 1578 (86%) had VL < 50 copies/mL at initiation. Of the 1578 suppressed, 267 (17%) were women, 654 (41%) were Black, 451 (29%) were Hispanic, and 469 (30%) had a BMI of ≥ 30; median age was 40  years (Table 1). Among those with CAB+RPV dose available, 1297 (84%) remained on CAB+RPV LA over a median follow-up of 7.4  months at study end. Among 1323 with VLs after first injection, the last VL measured was < 200 copies/mL in 99% (n=1305) and < 50 copies/mL in 94% (n=1237) (Table 2); all follow-up VLs were < 200 copies/mL in 96% (n=1272), and < 50 copies/mL in 84% (n=1115). Regardless of BMI, virologic suppression was maintained by ≥ 98% of individuals and only 1% experienced CVF over follow-up (Table 2).In this real-world cohort of PWH in the United States who received CAB+RPV LA injections, observations from the first 2 years suggest that this regimen is effective among individuals virologically suppressed at initiation. Furthermore, the regimen is consistently effective among those with high BMI.Michael Sension, MD, Gilead: Advisor/Consultant|Gilead: Honoraria|Viiv: Advisor/Consultant|Viiv: Grant/Research Support|Viiv: Honoraria Ricky K. Hsu, MD, Gilead Sciences: Advisor/Consultant|Gilead Sciences: Grant/Research Support|Gilead Sciences: Honoraria|Janssen: Advisor/Consultant|Janssen: Grant/Research Support|Janssen: Honoraria|Merck: Advisor/Consultant|Merck: Honoraria|ViiV Healthcare: Advisor/Consultant|ViiV Healthcare: Honoraria Jennifer S. Fusco, BS, Epividian, Inc.: Salary|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds Laurence Brunet, PhD, Epividian, Inc.: Salary|Epividian, Inc.: Stocks/Bonds Gayathri Sridhar, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Full Time Employee Vani Vannappagari, MBBS, MPH, PhD, GlaxoSmithKline: Stocks/Bonds|ViiV Healthcare: Employee Jean A. van Wyk, MBChB, MFPM, ViiV Healthcare Ltd: Stocks/Bonds Michael B. Wohlfeiler, JD, MD, AAHIVS, ViiV Healthcare: Serves as a PI on clinical trials, but does not receive personal compensation for this work  Gregory P. Fusco, MD, MPH, Epividian, Inc.: Board Member|Epividian, Inc.: Ownership Interest|Epividian, Inc.: Stocks/Bonds


Periprosthetic joint infection (PJI) is associated with significant morbidity. Management includes surgery and prolonged antibiotic treatment. Few studies have evaluated rates of acquired antimicrobial resistance in bacteria causing PJI. The aim of this study was to describe antimicrobial resistance profiles of bacteria causing PJI and to assess whether there was any apparent association between acquired resistance and clinical outcome.Patients at Mayo Clinic with first episodes of knee or hip PJI whose implants underwent sonication between January 2012 and December 2021 were studied. Sonicate fluid cultures from cement spacers or cultures yielding more than one microorganism were excluded. PJI was defined according to IDSA guidelines. Multidrug resistance was defined as non-susceptibility to at least one agent in three or more antimicrobial classes. Outcomes of PJI recurrence, need for further surgery with negative cultures or cultures yielding a new microorganism and amputation were assessed, within one year. Analysis was performed using SAS software version 9.4 (SAS Inc).S. epidermidis (n=82) and S. aureus (n=50), of which 68% and 30%, respectively, were methicillin resistant. Streptococci, Enterococci, Enterobacterales, and P. aeruginosa were found in 34,16, 8 and 3 cases; none were multidrug-resistant. No differences in PJI recurrence within one year were found in subjects with methicillin-resistant compared to methicillin-susceptible staphylococci , need for further surgery with negative cultures  or with cultures yielding a new microorganism , or amputation .256 PJI episodes were evaluated, 55% from knees and 45% from hips. Median patient age was 66 years, 52% were men. Resistance profiles are shown in the table. The most frequent microorganisms isolated were S. epidermidis with methicillin resistance found in 68% and multidrug resistance in 28%.Acquired antimicrobial resistance in PJI was most common in Matthew P Abdel, MD, OsteoRemedies: Royalties|Springer: Publishing royalties|Stryker: Royalties reltated to hip and knee implants 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


Outpatient parenteral antimicrobial therapy (OPAT) allows patients to complete intravenous (IV) or high risk oral medications outside the acute inpatient setting. Data regarding OPAT in patients with immunocompromise (PWIC) are sparse. PWIC represent a vulnerable population due to underlying comorbidities. This study evaluated OPAT clinical outcomes in PWIC at an academic medical center.This was a retrospective chart review of adult PWIC enrolled in our OPAT program between 1/2015-3/2023. Immunocompromising conditions included HIV/AIDS, stem cell or solid organ transplant, hematologic malignancy, solid tumor, or receipt of immunosuppressing medications. All patients were under the care of an immunocompromised ID specialist. Data collected included patient demographics, infection information, and OPAT outcomes including completion rates, readmission rates, OPAT failure, and death. OPAT failure was defined as death, 30-day infection-related readmission or 30-day OPAT-related complication. This study was exempt by the Institutional Review Board.50 patients were included. Demographics are in Table 1. Most (68%) patients completed OPAT therapy in the home, with 82% of courses being IV-only. Most (72%) patients received 1 antimicrobial agent, but 20% received 2 and 8% received 3 agents. The most common agents were daptomycin, ertapenem, and vancomycin.Staphylococci the most prevalent. Cytomegalovirus was the reason for OPAT in 4 patients.Infection information is in Table 2. Bloodstream infections and osteomyelitis were the most common. Most (82%) patients had an organism identified: 51% were Gram positive, with OPAT outcomes are in Table 3. OPAT failure occurred in 9 patients, including 1 death and 8 OPAT-related readmissions. Most (68%) patients completed the OPAT course within the specified time. Hospital readmissions were common: 46% had at least 1 readmission, though most readmissions were unrelated to OPAT. Vascular device issues and adverse drug reactions occurred in 12% and 20%, respectively.OPAT can be safely performed in PWIC with completion and complication rates comparable to non-immunocompromised cohorts. We observed high hospital readmission rates (46%) though a minority of readmissions were due to OPAT related issues.Monica V. Mahoney, PharmD, BCPS, BCIDP, FCCP, FIDSA, FIDP, BD Biosciences: Advisor/Consultant|Cidara Therapeutics: Advisor/Consultant|GSK: Advisor/Consultant|Merck: Grant/Research Support|Open Forum Infectious Diseases: Board Member|Open Forum Infectious Diseases: Associate Editor|Pfizer: Advisor/Consultant Carolyn D. Alonso, MD, Academy for Continued Healthcare Learning: Honoraria|AiCuris: Advisor/Consultant|American Society of Healthcare Pharmacists: Honoraria|Cidara Therapeutics: Advisor/Consultant|Clinical Care Options: Honoraria|Merck: Advisor/Consultant|Merck: Grant/Research Support


Immunosuppressed patients and those experiencing complicated UTIs are more susceptible to misdiagnosis by outdated standard of care (SOC) diagnostics; resulting in ineffective treatment and risk of severe complications. Shotgun metagenomic sequencing can act as a highly accurate tool in profiling urogenital pathogens in high-risk patients. We assessed the performance of a genomic-based urine assay in patients where the SOC failed to identify pathogens and compiled clinical metadata from medical records to evaluate if antimicrobial stewardship could be improved.Culture negative (no growth or < 100k CFU/mL) urine specimens (n=140) were collected from patients with pyuria and UTI symptoms then processed with the BIOTIA-ID Urine NGS Assay including DNA extraction, library preparation, Illumina NextSeq sequencing and analysis by BIOTIA-DX to identify urogenital pathogens. Findings were correlated with clinical metadata and administered antimicrobial therapies .Our assay yielded an average of 2M microbial reads per sample with 98.6% passing laboratory QC. Microbial species were detected in 82.6% of the culture-negative specimens, of which 36.8% were single organisms and 45.6% were polymicrobial infections. Different pathogen profiles were distinguished based on prior antibiotic use, catheterization, or specific comorbidities . 50% of septic patients showed single organism infections, while cancer patients had higher incidence of polymicrobial infections (52%). Higher prevalence of fungal infections (20%) were observed in catheterized patients, and those with prior antibiotic therapy within 30 days. Retrospective evaluation revealed 63% prescribed antimicrobials would not target the organisms detected. Further, 57% of the cases could have potentially de-escalated their treatment.High-risk patients frequently harbor atypical pathogens leading to inaccurate SOC testing and ineffective therapeutics. Genomic-based diagnostics may improve accuracy of urogenital pathogen detection and offer physicians precision therapeutics with better health outcomes while enhancing antimicrobial stewardship.Tiara Rivera, B.S., Biotia Inc.: Research Staff Sol Rey, BS, Biotia Inc: Researcher-Staff Xavier O. Jirau Serrano, MS, Biotia Inc: Research and development staff John C. Papciak, BS, Biotia Inc.: Staff Suraj S. Patel, n/a, Biotia Inc.: staff Bridget Harrison, B.A., Biotia Inc.: Clinical Program Manager- Staff Caitlin Otto, PhD, D(ABMM), Biotia Inc.: Staff Chris Mason, Ph.D., Biotia: Board Member|Biotia: Stocks/Bonds Heather L. Wells, MPH, PhD Candidate, Biotia, Inc.: Employee David C. Danko, Ph.D., Biotia Inc: Stocks/Bonds Niamh B. O'Hara, PhD, Biotia: Board Member|Biotia: 2 patents|Biotia: Ownership Interest|Biotia: Stocks/Bonds Mara Couto-Rodriguez, MS, Biotia Inc: Employee Dorottya Nagy-Szakal, MD PhD, Biotia Inc.: Employee|Biotia Inc.: Stocks/Bonds


Borrelia burgdorferi sensu lato strains expressing OspA serotypes 1-6. Background incidence rates (IRs) of health outcomes in Lyme disease endemic and non-endemic regions of the US may help to contextualize whether the frequencies of events reported during vaccine clinical trials or post-marketing are consistent with expected population level rates. The objective of this study was to estimate and compare IRs of health outcomes in Lyme disease endemic vs. non-endemic regions using US administrative claims data.A 6-valent vaccine (VLA15) is being tested in clinical trials for the prevention of Lyme disease caused by ® Plus commercial claims database was used to estimate IRs of 63 outcomes relevant to vaccine safety monitoring in the US during 01/01/2017-12/31/2019. Endemic regions were classified using 3-digit zip codes that overlapped with Lyme disease high incidence counties  according to the CDC. Analyses included all individuals aged ≥ 2 years with ≥ 1 year of enrollment. Outcomes were defined by ICD-10-CM diagnosis codes according to the literature or expert input and required ≥ 1 inpatient or ≥ 2 outpatient claims/codes. Crude IRs and 95% confidence intervals (CIs) were calculated for each outcome and compared between endemic vs. non-endemic regions using IR ratios (IRR).IQVIA PharMetricsTable 1 provides a summary of the IRs and IRRs for the 10 highest and 10 lowest ranking IRRs for health conditions by endemic region status. IRRs (95% CI) ranged from a low of 0.74  for systemic lupus erythematosus to a high of 2.14  for meningoencephalitis.The study population included 8.7M in endemic and 27.8M in non-endemic regions. Mean age was slightly higher in endemic (37.7 yrs [SD=18.9]) vs. non-endemic (36.8 yrs [SD=19.5]) cohorts, and 51% in both cohorts were female. This study identified potential differences between Lyme endemic and non-endemic regions of the US in background IRs of health conditions in vaccine safety monitoring. Differences in background IRs between endemic and non-endemic regions should be considered when contextualizing possible safety signals in clinical trials and post-marketing.Jill Dreyfus, PhD, MPH, Pfizer, Inc.: Employment|Pfizer, Inc.: Stocks/Bonds Swapna Munnangi, PhD, IQVIA: Employment Camilla Bengtsson, PhD, IQVIA: Employment|Pfizer, Inc: Advisor/Consultant Barbara Correia, PhD, IQVIA: Employee|Pfizer, Inc.: Advisor/Consultant Rejane Figueiredo, PhD, IQVIA: Biostatistician Sarah Galvin, BS, Pfizer, Inc.: Employment James H. Stark, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Michele Zawora, MD, FAAFP, Pfizer: Employment|Pfizer: Stocks/Bonds Mark Riddle, MD, DrPH, Pfizer: Employee salary Jason Maguire, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Qin Jiang, PhD, Pfizer: Employee|Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Juan Naredo Turrado, MS, IQVIA: Employee Steven Bailey, MD, MPH, MBA, Pfizer, Inc.: Employment


Inappropriate antibiotic prescribing continues to be an issue in the United States (US) despite a decline in prescription rate overall. Acute gastroenteritis (AGE) often requires medical attention but is generally managed conservatively. We describe antibiotic use among children with AGE in two healthcare settings.Clostridioides difficile detections were excluded due to high colonization rates in this group. A 20-point modified Vesikari score was calculated to categorize AGE severity .Children aged < 5 years with AGE were enrolled from December 2011-August 2021 at 7 New Vaccine Surveillance Network (NVSN) sites across the US. Inpatients (IP) and emergency department (ED) patients with diarrhea (≥3 episodes) and/or vomiting (≥1 episode) within 24 hours, without history of noninfectious diarrhea or immunodeficiency were included. Stools were collected within 10 days of symptom onset and tested for enteric pathogens by validated molecular methods. Antibiotic use during AGE visit was collected via medical chart abstraction; antibiotic use was mostly empiric and not driven by test results. Children < 2 years with Enteropathogenic E. coli .Among 21,194 enrolled children , median IP age was 14 months (IQR 5-28) and ED age 18 months (IQR 9-32). Most were male (IP and ED=54%) and white (IP=61% and ED=43%). Antibiotic use for AGE was noted in 994 (26%) IP and 765 (4%) ED cases; the majority were infants  and had severe AGE . Fever was more common among antibiotic recipients versus non-recipients . Antibiotic use across study years was low in ED (2-10%) but higher in IP (19-31%) . Among tested antibiotic recipients, the predominant pathogens detected were norovirus  and rotavirus  without bacterial codetection, and Overall antibiotic use for AGE among enrolled children was low but was higher among IP, especially in infants and those with severe AGE. Antibiotic use for viral AGE in both ED and IP settings highlights the need to improve antibiotic stewardship among children with AGE.Rangaraj Selvarangan, BVSc, PhD, D(ABMM), 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 Christopher J. Harrison, MD, GSK: Grant/Research Support|Pfizer: 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 Geoffrey A. Weinberg, MD, Merck & Co: Honoraria 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 Mary A. Staat, MD, MPH, CDC: Grant/Research Support|Cepheid: Grant/Research Support|Merck: Grant/Research Support|NIH: Grant/Research Support|Pfizer: Grant/Research Support|Up-To-Date: Honoraria John V. Williams, MD, Merck: Grant/Research Support|Quidel: Board Member Marian G. Michaels, MD, MPH, Merck: Grant/Research Support|Viracor: Grant/Research Support


Scientific Reports 10.1038/s41598-022-12134-3, published online 17 May 2022Correction to: The Acknowledgements section in the original version of this Article was incomplete. It now reads:“The authors gratefully acknowledge the financial support by the following projects: H2020-MSCA-RISE-2017, CanBioSe 778157 (II), SONATA BIS 6 National Science Centre, Poland, under research Grant Number 2016/22/E/ST3/00458 , National Centre for Research and Development under grant NanoHEART/2021 , and Ministry of Education and Science SPUB—41/E-336/SPUB/SP/2019 . The authors would like to thank Katarzyna Staszak from Poznan University of Technology for her help in performing Zn release studies.”The original Article has been corrected.


Prevention of surgical site infections (SSIs) involves implementation of numerous steps including ultraclean air in the operating room (OR). Despite all efforts, particles in the room air may exist and some of these particles may be live pathogens that can potentially cause subsequent SSI. This prospective study aimed to determine and compare the nature and quantity of microbes in the operating room, as detected from the inlet flow of an ultraviolet filtration unit, and the efficacy of the unit to remove particles and creating clean room air (the outlet flow).This prospective study was conducted at a single institution, where primary total joint arthroplasty and spine surgeries were performed. The OR was fitted with a positive ventilation system. In addition, a filtration unit with a crystalline ultraviolet unit (C-UVC) was placed in the OR. The inflow and outflow air from the unit was sampled using specialized swabs at the beginning and at conclusion of each procedure. Additional surgical-related variables were also recorded at each time of sampling. Swabs were processed for culture and Next-Generation Sequencing.Operating room floor planThe filtration unit with ultraviolet-C light is represented with a red rectangle and doors (source of contamination) are represented by dark gray rectangles.Air flow and air swabs collection.The mean length of the surgical procedures sampled was 68 ± 13 minutes. Overall, 19 out of 200 (9.5%) swabs isolated microorganisms. Inflow swabs were positive at a higher rate , compared to the outcoming air swabs. A wide variety of Gram-positive, Gram-negative, anaerobic bacteria, and fungi (only in the inflow swabs) were isolated. The detection of microorganisms was also higher in surgical procedures with a higher number of door openings .Surgical-related variables collected at air swab sampling.Microorganisms are present in the operating room air. A specialized filtration unit with a C-UVC light was effective in filtering these microorganisms in the majority of cases.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


The COVID-19 pandemic highlighted the need for better data to understand how ventilation may impact respiratory virus transmission. We evaluated if there was an association between respiratory viruses detected in school room air samples and nasal swabs from students/ staff in the same room.We performed air and respiratory sampling to detect respiratory viruses at 3 time points between Feb 27 - Mar 28, 2023 in 2 elementary schools. Three classrooms, a multipurpose room, and school nurse’s office in each school had 1 air sample/ room collected using Thermo Scientific AerosolSense™ sampler during 8 school hours. Concomitant respiratory viral testing, using self-collected nasal swabs, was performed in students/ staff enrolled in a respiratory virus surveillance school testing program. Air and respiratory specimens were tested for adenovirus (AdV); coronaviruses (CoV) 229E, HKU1, NL63, OC43; human metapneumovirus (hMPV), influenza A and B (Flu), parainfluenza virus 1-4 (PIV), respiratory syncytial virus (RSV), rhinovirus/ enterovirus (RV/EV), and SARS-CoV-2 using the Hologic® Panther Fusion® Respiratory Assay. Detected respiratory viruses in room air and respiratory samples were compared to determine likelihood of capturing current human respiratory viral infections in room air and additional viruses circulating from unsampled students/ staff in the same room. RV and AdV in human respiratory samples were typed by partial genomic sequencing to understand if viruses were similar.Ten rooms, including 6 classrooms with ≈25 people/ room, were sampled at 3 occasions. At least 1 respiratory virus was detected in 27/ 30 (90%) air samples. 59 samples were obtained from 20 students and 5 staff in these rooms; 24 (41%) were positive for ≥1 virus and 11/24 (46%) rooms with concomitant air and respiratory samples had the same viruses detected (Table). RV typing demonstrates that both participants from Room E, Round 1 and 2 had RV-B27. Both participants from Room F, Round 2 with single AdV infections had AdV B3.Concomitant respiratory virus surveillance in air samples and students/ staff can be performed to better understand the role of ventilation and respiratory virus transmission. Additional studies, including sequencing data and symptom assessment, are needed.Rangaraj Selvarangan, BVSc, PhD, D(ABMM), 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


Respiratory syncytial virus (RSV) is an important cause of lower respiratory tract illness (LRTI) in older adults. The search for an effective RSV vaccine was hindered by poor functional immunogenicity of early vaccine candidates that did not have F antigens stabilized in the prefusion state. RSVpreF, Pfizer’s bivalent stabilized prefusion F subunit vaccine candidate containing preF antigens against two major RSV subgroups (A and B), elicited robust neutralizing responses in phase 1/2 studies.The RSV Vaccine Efficacy Study in Older Adults Immunized Against RSV Disease (RENOIR) is a phase 3, multicenter, randomized, double-blinded, placebo-controlled study evaluating vaccine efficacy (VE) to prevent LRTI in adults ≥60 years of age over two RSV seasons (NCT05035212). Participants were randomly assigned (1:1 ratio) to receive a single intramuscular injection of RSVpreF at a dose of 120μg or placebo. The study demonstrated a VE of 88.9% for LRTI-RSV with ≥3 symptoms at the end of the first RSV season. A secondary objective was to describe the immune responses induced by RSVpreF following vaccination. The immunogenicity subset included 1150 participants enrolled from sites in the United States and Japan.Here we report the immunogenicity results one month after RSVpreF vaccination. The neutralization titer geometric mean fold rises (GMFRs) ranged from 11.6 to 12.7 for RSV A and B, respectively, and GMFRs for combined RSV A/B neutralizing responses ranged from 12.0 to 13.0 for subgroups stratified by age . RSV A/B GMFRs in participants with prespecified chronic conditions were similar to or higher than those without, with 11.4, 13.0 and 14.8, respectively, for subgroups stratified based on none, at least one prespecified chronic medical condition or at least one chronic cardiopulmonary condition.RSV Neutralizing GMTs Before and 1 Month Postvaccination 1 and Subgroup AnalysisHigh RSV neutralizing titers were observed one month after RSVpreF vaccination in adults 60 years and older, consistent with prior phase 1/2 studies. The study further shows similarly robust responses across age subgroups and baseline chronic conditions. Although there is no established correlate of protection, these high antibody responses corresponded with high RSVpreF VE in the first RSV season.Agnieszka Zareba, MD PhD, Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Qin Jiang, PhD, Pfizer: Employee|Pfizer: Employee|Pfizer: Stocks/Bonds|Pfizer: Stocks/Bonds Daniel P. Eiras, MD, MPH, Pfizer, Inc.: Stocks/Bonds Michael Patton, B.Sc., Pfizer Inc.: Employee|Pfizer Inc.: Stocks/Bonds Kumar Ilangovan, MD, MSPH, MMCi, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Elliot N. DeHaan, MD, Pfizer: Employee|Pfizer: Stocks/Bonds Tarek Mikati, MD,MPH, Pfizer: Stocks/Bonds Elena Kalinina, PhD, Pfizer: Pfizer employee|Pfizer: Stocks/Bonds David Cooper, PhD, Pfizer, Inc.: Stocks/Bonds Kenneth Koury, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Annaliesa S. Anderson, PhD, Pfizer: Employee|Pfizer: Stocks/Bonds Kena A. Swanson, Ph.D., Pfizer: Employee|Pfizer: Stocks/Bonds William C. Gruber, MD, Pfizer, Inc.: Employee|Pfizer, Inc.: Stocks/Bonds Alejandra C. Gurtman, M.D., Pfizer: Employee|Pfizer: Stocks/Bonds Beate Schmoele-Thoma, MD, Pfizer: Stocks/Bonds