Respiratory syncytial virus (RSV) caused approximately 100,000-160,000 hospitalizations annually in adults aged ≥60 years in the United States (US) before RSV vaccine introduction. In 2023, two vaccines were recommended for prevention of severe RSV disease in adults aged ≥60 years using shared clinical decision making. In 2024, a third product was licensed, and all three available vaccines were recommended for all adults aged ≥75 years and for adults aged 60-74 years at increased risk of severe RSV disease. We assessed post-licensure vaccine effectiveness (VE) to inform future recommendations and public communications. VISION is a multi-site electronic health record-based study including >200 hospitals in the US. Adults aged ≥60 years hospitalized with RSV-like illness and tested for RSV were included. Cases had a positive molecular or antigen RSV test; controls had a negative molecular RSV test. Critical illness included admission to the intensive care unit or in-hospital death. VE against hospitalization and critical illness was calculated using a test negative design as (1-adjusted odds ratio) x 100% where the odds ratio compares odds of vaccination in cases and controls after adjusting for confounders. Results were stratified by time since RSV vaccination, age group, and immunocompromised status. Among 83,652 hospitalizations during October 2023-March 2024 and October 2024-March 2025, VE was 62% (95% CI: 56-67%, Table) against RSV-associated hospitalization, median 279 days after RSV vaccination. VE was 83% (95% CI: 73-89%) at 14-59 days after vaccination and 42% (95% CI: 30-53%) at least 1 year after vaccination (median 429 days). VE against RSV-associated critical illness was 69% (95% CI: 55-78%), median 277 days after vaccination. VE was similar by age group and among those with and without immunocompromising conditions. RSV vaccines are effective at preventing severe RSV and have the potential to reduce the burden of RSV-associated hospitalizations among older adults, although waning protection was apparent during the second season after vaccination. Ongoing monitoring of RSV VE is warranted to ensure vaccines are working as expected, to understand duration of protection, and to inform policy decisions. All Authors: No reported disclosures

CDC recommends annual influenza vaccination for all persons aged ≥ 6 months. We estimated 2024–2025 seasonal influenza vaccine effectiveness (VE) against influenza–associated hospitalizations among adults.Figure 1.2024–2025 seasonal influenza vaccine effectiveness against influenza–associated hospitalizations among adults aged ≥ 18 years — VISION Network, October 2024–March 2025Abbreviations: CI = Confidence interval; ICU = Intensive care unit; IQR = Interquartile range; VE = vaccine effectiveness.a) Patients were considered vaccinated if they received ≥1 2024–2025 influenza vaccine dose ≥14 days before the index date, defined as the earlier date of the most recent influenza test and the hospital admission date.b) VE was estimated using multivariable logistic regression models comparing the odds of receipt of ≥1 2024–2025 influenza vaccine dose versus no dose among cases and controls. Models were adjusted for age, sex, race and ethnicity, calendar day, and healthcare system. Age and calendar day were treated as natural cubic splines with 4 degrees of freedom.c) Influenza A and B coinfections were excluded from influenza A and B case counts and from VE estimates against influenza A and B.d) Patients were considered immunocompromised if they had ≥1 ICD-10 discharge diagnosis code for any of the following conditions: hematologic malignancy, solid malignancy, bone marrow transplant, solid organ transplant, rheumatologic/inflammatory disorder, other intrinsic immunodeficiency condition, or HIV/AIDS.e) To estimate VE against ICU admission, cases were restricted to encounters with ICU admission and no in-hospital death. Data from the VISION Network were used to estimate influenza VE using a test-negative, case-control design. The analysis included hospitalizations among adults aged ≥ 18 years with ≥ 1 acute respiratory illness (ARI)–associated ICD-10 discharge diagnosis code from October 1, 2024–March 7, 2025 in six US healthcare systems. Cases were ARI hospitalizations with a positive molecular influenza test within 10 days before to 72 hours after the admission date. Controls were ARI hospitalizations with a negative molecular influenza test during the same interval. VE was estimated using multivariable logistic regression comparing the odds of receipt of ≥ 1 2024–2025 influenza vaccine dose versus no dose among cases and controls. VE models were adjusted for age, sex, race and ethnicity, calendar day, and healthcare system. A total of 31,338 ARI hospitalizations met inclusion criteria, including 4,969 cases and 26,369 controls (Figure). Overall VE against influenza–associated hospitalizations was 46% (95% CI=43–50%) with a median time since vaccination of 79 days (IQR=50–107). When stratified by time since vaccination, VE was 46% (95% CI=38–53%) at 14–59 days, 41% (95% CI=36–45%) at 60–119 days, and 9% (95% CI=-1 to 19%) at ≥ 120 days. VE was 46% (95% CI=42–50%) against influenza A and 65% (95% CI=41–80%) against influenza B. Among immunocompetent and immunocompromised adults, VE was 49% (95% CI=45–53%) and 33% (95% CI=23–42%), respectively. VE against influenza–associated intensive care unit (ICU) admission was 49% (95% CI=38–58%) and against in-hospital death was 48% (95% CI=31–62%). 2024–2025 seasonal influenza vaccines provided protection against influenza–associated hospitalizations among adults with evidence of decreased VE ≥ 120 days after vaccination. VE point estimates were higher against influenza B than against influenza A and among immunocompetent versus immunocompromised adults. VE against influenza–associated ICU admission and in-hospital death were similar to that against hospitalization. Zachary Weber, PhD, MS, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Duck-Hye Yang, PhD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Stephanie Irving, MHS, Westat: Grant/Research Support Sara Y. Tartof, PhD, MPH, Centers for Disease Control and Prevention: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Malini B. DeSilva, MD, MPH, Centers for Disease Control and Prevention Vaccine Safety Datalink: Grant/Research Support|Westat: Grant/Research Support Padma Kppolu, MPH, Westat: Grant/Research Support S. Bianca Salas, MPH, Centers for Disease Control and Prevention: Grant/Research Support|Pfizer: Grant/Research Support Lina S. Sy, MPH, AstraZeneca: Grant/Research Support|Dynavax: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Moderna: Grant/Research Support Bruno Lewin, MD, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support Richard Contreras, MS, Centers for Disease Control and Prevention: Grant/Research Support Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support John R. Hansen, MPH, Centers for Disease Control and Prevention: Grant/Research Support Lawrence Block, MPH, MPA, Centers for Disease Control and Prevention: Grant/Research Support Karen B. Jacobson, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research Support Catia Chavez, MPH, Westat: Grant/Research Support Adam Yates, PhD, Beehive Study: Grant/Research Support|Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Lindsey Kirshner, MPH, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support Charlene E. McEvoy, MD, MPH, Astra Zeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|Department of Defense: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|National Institutes of Health: Grant/Research Support|PCORI: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support

On June 26, 2024, the CDC updated respiratory syncytial virus (RSV) vaccine recommendations to a single dose of RSV vaccine for all adults aged ≥ 75 years and adults aged 60-74 years with increased risk of severe RSV disease. Using electronic health record (EHR) data from the VISION platform, we described characteristics of patients testing negative for RSV who did and did not receive an RSV vaccine and assessed factors associated with RSV vaccine receipt.Figure 1:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccination among test-negative patients with an emergency department (ED) encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=23,403 patientsFigure 2:Characteristics associated with receipt of respiratory syncytial virus (RSV) vaccine among test-negative patients with an inpatient encounter for RSV-like illness (RLI) during the 2024-2025 season in the VISION network, N=25,020 patients Patients with ≥ 1 emergency department (ED) or inpatient encounter at any of 6 participating health systems in 8 states with RSV-like illness (RLI) during October 1, 2024-March 31, 2025 were included. Vaccination status was ascertained from EHR, state and city immunization information systems, and medical claims. Patients who tested positive for SARS-CoV-2 or influenza viruses at the same RLI encounter were excluded. Patient age, sex, race and ethnicity, Medicaid status, number of underlying medical conditions, month of medical encounter, and documented receipt of COVID-19 or influenza vaccines were evaluated as covariates when assessing the odds of vaccination. The best fitting multivariable logistic regression models using Bayesian Information Criterion were chosen. Among 48423 included patients, 2113 (4.4%) had documented RSV vaccine receipt. The odds of RSV vaccination differed by site and increased with calendar time and age. Compared to patients aged 60-64 years, those aged ≥ 75 years were more likely to have received an RSV vaccine (ED: aOR: 3.6, 95%CI: 2.7-4.8, Figure 1; inpatient: aOR: 2.3, 95%CI: 1.7-3.0, Figure 2). Receipt of both influenza and COVID-19 vaccine within the same season had the strongest association with RSV vaccination in both the ED (aOR: 14.88, 95%CI: 11.87-18.89, Figure 1) and hospital setting (aOR: 20.04, 95%CI: 16.20-25.03, Figure 2). Receipt of other respiratory viral vaccines was the strongest indicator of RSV vaccination in the 2024-2025 RSV season in patients testing negative for RSV among all demographic and clinical characteristics considered. RSV vaccination was lower among those aged 60-64 years than older patients. These findings inform future methods to estimate vaccine effectiveness and inform policy implementation. Gabriela Vazquez-Benitez, PhD, MSc, AbbVie: research funding not related to this study|Sanofi: Grant funding for other research not related to this study Stephanie Irving, MHS, Westat: Grant/Research Support Nicola P. Klein, MD, PhD, AstraZeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|Janssen: Grant/Research Support|Merck: Grant/Research Support|Moderna: Grant/Research Support|Pfizer: Grant/Research Support|Sanofi Pasteur: Grant/Research Support|Seqirus: Grant/Research Support Shaun J. Grannis, MD, MS, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health NCATS: Grant/Research Support|National Institutes of Health NIMH: Grant/Research Support Toan Ong, PhD, Centers for Disease Control and Prevention via Westat: Grant/Research Support|Patent Title: Systems and Methods For Record Linkage: Patent Number: PCT/US2018/047961|PCORI: Travel Support|Regenstrief Institute: Advisor/Consultant|Regenstrief Institute: Travel Support Sarah W. Ball, MPH, ScD, Centers for Disease Control and Prevention, Contract #200-2019-F-06819: Grant/Research Support|Centers for Disease Control and Prevention, Contract #75D30121D12779: Grant/Research Support|Novavax: Grant/Research Support Jingran Cao, MS, Sanofi Pasteur: Grant/Research Support Charlene E. McEvoy, MD, MPH, Astra Zeneca: Grant/Research Support|Centers for Disease Control and Prevention: Grant/Research Support|Department of Defense: Grant/Research Support|GlaxoSmithKline: Grant/Research Support|National Institutes of Health: Grant/Research Support|PCORI: Grant/Research Support Ousseny Zerbo, PhD, Centers for Disease Control and Prevention: Grant/Research Support|Moderna: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support John R. Hansen, MPH, Centers for Disease Control and Prevention: Grant/Research Support Lawrence Block, MPH, MPA, Centers for Disease Control and Prevention: Grant/Research Support Karen B. Jacobson, MD, MPH, Centers for Disease Control and Prevention: Grant/Research Support|National Institutes of Health: Grant/Research Support|Pfizer: Grant/Research Support William F. Fadel, PhD, Centers for Disease Control and Prevention: Grant/Research Support Catia Chavez, MPH, Westat: Grant/Research Support Karthik Natarajan, PhD, Centers for Disease Control and Prevention: Grant/Research Support Ryan E. Wiegand, PhD, Merck & Co., Inc.: Stocks/Bonds (Public Company)|Sanofi S.A.: Stocks/Bonds (Public Company)

Importance:SARS-CoV-2 continues to evolve, population immunity changes, and COVID-19 vaccine formulas have been updated, necessitating ongoing COVID-19 vaccine effectiveness (VE) monitoring. Objectives:To evaluate the VE of 2023-2024 COVID-19 vaccines against COVID-19-associated emergency department (ED) and urgent care (UC) encounters, hospitalizations, and critical illness, including during XBB- and JN.1-predominant periods. Design, Setting, and Participants:This test-negative design VE case-control study was conducted using data from September 21, 2023, to August 22, 2024, from EDs, UC centers, and hospitals in 6 US health care systems. Eligible adults 18 years or older with COVID-19-like illness and molecular or antigen testing for SARS-CoV-2 were studied. Case patients were those with a positive molecular or antigen test result; control patients were those with a negative molecular test result. Exposure:Receipt of 2023-2024 (monovalent XBB.1.5) COVID-19 vaccination with products approved or authorized for use in the US. Main Outcomes and Measures:Main outcomes were COVID-19-associated ED and UC encounters, hospitalizations, and critical illness (admission to the intensive care unit or in-hospital death). VE was estimated comparing the odds of receipt of the 2023-2024 COVID-19 vaccine with no receipt among case and control patients. Results:Among 345 639 eligible ED and UC encounters in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 53 [34-71] years; 209 087 [60%] female), 37 096 (11%) had a positive SARS-CoV-2 test result. VE against COVID-19-associated ED and UC encounters was 24% (95% CI, 21%-26%) during 7 to 299 days after vaccination. Among 111 931 eligible hospitalizations in immunocompetent adults 18 years or older with COVID-19-like illness and available test results (median [IQR] age, 71 [58-81] years), 10 380 (9%) had a positive SARS-CoV-2 test result. During 7 to 299 days after vaccination, VE was 29% (95% CI, 25%-33%) against COVID-19-associated hospitalization and 48% (95% CI, 40%-55%) against COVID-19-associated critical illness. VE was highest 7 to 59 days after vaccination (VE against ED and UC encounters 49%; 95% CI, 46%-52%; hospitalization, 51%; 95% CI, 46%-56%; critical illness, 68%; 95% CI, 56%-76%) and then waned (VE 180-299 days after vaccination against ED and UC encounters, -7% [95% CI, -13% to -2%]; hospitalization, -4% [95% CI, -14% to 5%]; and critical illness, 16% [95% CI, -6 to 34%]). Conclusions and Relevance:In this case-control study of VE, 2023-2024 COVID-19 vaccines were estimated to provide additional effectiveness against medically attended COVID-19, with the highest and most sustained estimates against critical illness. These results highlight the importance of receiving recommended COVID-19 vaccination for adults 18 years or older.

BACKGROUND:Respiratory syncytial virus vaccines first recommended for use during 2023 were efficacious against lower respiratory tract disease in clinical trials. Limited real-world data regarding respiratory syncytial virus vaccine effectiveness are available. To inform vaccine policy and address gaps in evidence from the clinical trials, we aimed to assess the effectiveness against respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years. METHODS:We conducted a test-negative design analysis in an electronic health records-based network in eight states in the USA, including hospitalisations and emergency department encounters with respiratory syncytial virus-like illness among adults aged at least 60 years who underwent respiratory syncytial virus testing from Oct 1, 2023, to March 31, 2024. Respiratory syncytial virus vaccination status at the time of the encounter was derived from electronic health record documentation, state and city immunisation registries, and, for some sites, medical claims. Vaccine effectiveness was estimated by immunocompromise status, comparing the odds of vaccination among respiratory syncytial virus-positive case patients and respiratory syncytial virus-negative control patients, and adjusting for age, race and ethnicity, sex, calendar day, social vulnerability index, number of underlying non-respiratory medical conditions, presence of respiratory underlying medical conditions, and geographical region. FINDINGS:Among 28 271 hospitalisations for respiratory syncytial virus-like illness among adults aged at least 60 years without immunocompromising conditions, vaccine effectiveness was 80% (95% CI 71-85) against respiratory syncytial virus-associated hospitalisations, and vaccine effectiveness was 81% (52-92) against respiratory syncytial virus-associated critical illness (ICU admission or death, or both). Among 8435 hospitalisations for respiratory syncytial virus-like illness among adults with immunocompromising conditions, vaccine effectiveness was 73% (48-85) against associated hospitalisation. Among 36 521 emergency department encounters for respiratory syncytial virus-like illness among adults aged at least 60 years without an immunocompromising condition, vaccine effectiveness was 77% (70-83) against respiratory syncytial virus-associated emergency department encounters. Vaccine effectiveness estimates were similar by age group and product type. INTERPRETATION:Respiratory syncytial virus vaccination was effective in preventing respiratory syncytial virus-associated hospitalisations and emergency department encounters among adults aged at least 60 years in the USA during the 2023-24 respiratory syncytial virus season, which was the first season after respiratory syncytial virus vaccine was approved. FUNDING:The Centers for Disease Control and Prevention.

Laboratory algorithms using Acid-Fast Bacilli staining and Mycobacterium tuberculosis (Mtb) polymerase chain reaction (PCR) are often used to remove isolation precautions. A retrospective case review of 52 patients with culture-confirmed pulmonary Mtb revealed 4 subjects with negative sputum Acid-Fast Bacilli smears and negative Mtb PCRs. All had significant risk factors for Mtb and had a positive interferon-gamma release assay. A negative PCR test result does not exclude an Mtb diagnosis.

Background:Plasma microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying microbial DNA in plasma. However, data are needed to define the clinical scenarios where this tool offers the highest clinical benefit. Methods:We conducted a prospective multicenter observational study that evaluated the impact of plasma mcfDNA sequencing compared with usual care testing among adults with hematologic malignancies. This is a secondary analysis of an expanded cohort that evaluated the clinical utility of plasma mcfDNA sequencing across prespecified and adjudicated outcomes. We examined the percentage of participants for whom plasma mcfDNA sequencing identified a probable cause of pneumonia or clinically relevant nonpneumonia infection. We then assessed potential changes in antimicrobial therapy based on plasma mcfDNA sequencing results and the potential for early mcfDNA testing to avoid bronchoscopy and its associated adverse events. Results:Of 223 participants, at least 1 microbial detection by plasma mcfDNA sequencing was adjudicated as a probable cause of pneumonia in 57 (25.6%) and a clinically relevant nonpneumonia infection in 88 (39.5%). A probable cause of pneumonia was exclusively identified by plasma mcfDNA sequencing in 23 (10.3%) participants. Antimicrobial therapy would have changed for 41 (18.4%) participants had plasma mcfDNA results been available in real time. Among the 57 participants with a probable cause of pneumonia identified by plasma mcfDNA sequencing, bronchoscopy identified no additional probable cause of pneumonia in 52 (91.2%). Conclusions:Plasma mcfDNA sequencing could improve management of both pneumonia and other concurrent infections in immunocompromised patients with suspected pneumonia.

Background Infection prevention employs an algorithm that includes 3 negative sputum Acid Fast Bacilli (AFB) stains and 2 negative nucleic acid amplification (NAA) polymerase chain reaction (PCR) tests along with review of clinical findings and risk factors for Mycobacterium tuberculosis (MTb) to clear patients. NAA tests on smear negative specimens have a higher likelihood of false negative results. This has implications in the hospital setting and for public health. Methods Retrospective review of 648 unique MTb PCR data from January 1, 2020-November 31, 2022 with 16 positive results (8 had positive AFB smears; 16 grew MTb on culture). We identified one patient with 3 negative AFB smears and 3 negative MTb PCR tests who grew MTb on culture. Results The patient with discordant MTb PCR testing/culture results was a 16-year-old female who presented with 4 months of cough. She had recently immigrated to the US from Guatemala. She was febrile with tachycardia and tachypnea. Chest x-ray had patchy hazy opacities in the left mid to lower lung. She was placed on airborne precautions during specimen collection and precautions were removed after testing negative on AFB stain and PCR. The local health department took over management of the patient and she was treated with 4 drug anti-Tb therapy for 1 week and then it was discontinued based on the results. Approximately 2 weeks later, the patient's AFB cultures became positive and it grew MTb. Patient was restarted on anti-Tb treatment. Conclusions MTb PCR testing has high sensitivity and high specificity to rule in or rule out MTb. However, a negative NAA test result does not exclude the possibility of a positive culture. Infection Preventionists must ensure that clinical findings and MTb risk factors are thoroughly reviewed along with the laboratory data before removing isolation precautions and be aware that false negative tests can occur. Infection prevention employs an algorithm that includes 3 negative sputum Acid Fast Bacilli (AFB) stains and 2 negative nucleic acid amplification (NAA) polymerase chain reaction (PCR) tests along with review of clinical findings and risk factors for Mycobacterium tuberculosis (MTb) to clear patients. NAA tests on smear negative specimens have a higher likelihood of false negative results. This has implications in the hospital setting and for public health. Retrospective review of 648 unique MTb PCR data from January 1, 2020-November 31, 2022 with 16 positive results (8 had positive AFB smears; 16 grew MTb on culture). We identified one patient with 3 negative AFB smears and 3 negative MTb PCR tests who grew MTb on culture. The patient with discordant MTb PCR testing/culture results was a 16-year-old female who presented with 4 months of cough. She had recently immigrated to the US from Guatemala. She was febrile with tachycardia and tachypnea. Chest x-ray had patchy hazy opacities in the left mid to lower lung. She was placed on airborne precautions during specimen collection and precautions were removed after testing negative on AFB stain and PCR. The local health department took over management of the patient and she was treated with 4 drug anti-Tb therapy for 1 week and then it was discontinued based on the results. Approximately 2 weeks later, the patient's AFB cultures became positive and it grew MTb. Patient was restarted on anti-Tb treatment. MTb PCR testing has high sensitivity and high specificity to rule in or rule out MTb. However, a negative NAA test result does not exclude the possibility of a positive culture. Infection Preventionists must ensure that clinical findings and MTb risk factors are thoroughly reviewed along with the laboratory data before removing isolation precautions and be aware that false negative tests can occur.

Abstract Background Microbial cell-free DNA (mcfDNA) sequencing can establish the etiology of multiple infectious syndromes by identifying pathogen DNA from the plasma of infected patients. Here, we describe the potential impact of a positive mcfDNA result on clinical decision making among immunocompromised adults with suspected pneumonia. Methods This prospective observational study evaluated the potential utility of mcfDNA sequencing in adults with active hematological malignancies undergoing a diagnostic bronchoscopy for pneumonia at 10 US Medical Centers as part of the PICKUP Study (Abstract # 544 IDWeek 2022). Plasma mcfDNA was collected on all participants at the time of bronchoscopy. Clinical impact of the mcfDNA sequencing results vs usual care (UC) testing – including bronchoscopy- were adjudicated and then compared for: 1) identification of probable cause of pneumonia or clinically significant non-pulmonary infection and 2) potential changes to antimicrobial therapy if mcfDNA sequencing results were available to treating clinicians. Results Of 223 participants analyzed, median (IQR) age was 62 (50-69) years and 72 (32.3%) were female. Plasma mcfDNA identified a probable cause of pneumonia in 57/223 (25.6%, 95% CI 20.0-31.8) participants and could have changed antimicrobial therapy in 21/57 (36.8%, 95% CI 24.4-50.7). A probable cause of pneumonia was identified by mcfDNA in 23/223 (10.3%, 95% CI 6.7-15.1) participants when no cause was identified by UC, and these detections could have resulted in an antimicrobial change in 17/23 (73.9%, 95% CI 51.6-89.8). A clinically relevant non-pulmonary infection was identified in 88/223 (39.5%, 95% CI 33.0-46.2) participants and antimicrobial therapy could have changed in 22/88 (25.0%, 95% CI 16.4-35.4). Collectively, antimicrobial therapy could have changed for 41/223 (18.4%, 95% CI 13.5-24.1) participants if mcfDNA results were available to treating clinicians. Conclusion Positive plasma mcfDNA sequencing results could have supported changes in clinical management for pneumonia and non-pulmonary infections among immunocompromised patients undergoing bronchoscopy. Further studies are needed to refine the optimal timing of mcfDNA in relation to UC testing and establish the impact of real-time mcfDNA results on patient outcomes. Disclosures Deng B. Madut, MD, Karius: Advisor/Consultant Roy F. Chemaly, MD/MPH, Eurofins-VViracor: Grant/Research Support|Karius: Advisor/Consultant Sanjeet S. Dadwal, MD, FACP, FIDSA, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Ansun Biopharma: Grant/Research Support|Aseptiscope, Inc: Stocks/Bonds|Astellas: Honoraria|Karius: Grant/Research Support|Matinas Biopharma: Stocks/Bonds|Merck: Advisor/Consultant|Merck: Grant/Research Support|Pfizer/Amplyx: Grant/Research Support|Takeda: Advisor/Consultant|Takeda: Honoraria|Viracor: Honoraria Joshua A. Hill, MD, Allovir: Advisor/Consultant|Allovir: Grant/Research Support|Century Therapeutics: Advisor/Consultant|Covance/CSL: Advisor/Consultant|Deverra: Grant/Research Support|Eversana Life Science Services, LLC: Advisor/Consultant|GeoVax: Grant/Research Support|Gilead: Advisor/Consultant|Gilead: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|Merck: Grant/Research Support|Moderna DSMB: Advisor/Consultant|Octapharma AG: Advisor/Consultant|OptumHealth: Advisor/Consultant|Oxford Immunotec: Grant/Research Support|Pfizer (previously Amplyx/Medpace): Advisor/Consultant|Senti BioSciences, Inc: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Takeda: Grant/Research Support|Up-to-Date: Advisor/Consultant Yeon Joo Lee, MD, MPH, AiCuris: institutional research support for clinical trials|Karius: institutional research support for clinical trials|Merck: Grant/Research Support|Scynexis: institutional research support for clinical trials Ghady Haidar, MD, Allovir: Grant/Research Support|AstraZeneca: Advisor/Consultant|AstraZeneca: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support|NIH: Grant/Research Support Alfred Luk, MD, Bill & Melinda Gates Foundation: Grant/Research Support|Karius: Advisor/Consultant|Karius: Grant/Research Support Fareed Khawaja, MBBS, MEDSCAPE: Honoraria|Viracor: Grant/Research Support Genovefa Papanicolaou, MD, Allovir: Advisor/Consultant|Amplyx: Advisor/Consultant|Astellas: Advisor/Consultant|Cidara: Advisor/Consultant|CSL Behring: Advisor/Consultant|DSMC: Advisor/Consultant|Merck: Advisor/Consultant|Merck: Grant/Research Support|Merck: institutional research support for clinical trials|MSD: Advisor/Consultant|Octapharma: Advisor/Consultant|Partners Rx: Advisor/Consultant|Shire/Takeda: institutional research support for clinical trials|Symbio: Advisor/Consultant|Symbio: Advisor/Consultant|Takeda: Advisor/Consultant|Vera Pharma: Advisor/Consultant Micah T. McClain, MD, PhD, Biomeme Inc: Methods to diagnose and treat acute respiratory infections Eileen K. Maziarz, MD, Karius, Inc: Advisor/Consultant Robert Bigelow, PhD, Covidien: Stocks/Bonds|Elixir Medical: Advisor/Consultant|Johnson & Johnson: Stocks/Bonds|Mckesson: Stocks/Bonds|Merck: Stocks/Bonds|Organon: Stocks/Bonds|Pfizer: Stocks/Bonds|Sanofi: Stocks/Bonds|Viatris: Stocks/Bonds Daniel Lupu, MD, PHD, Karius Inc: Employee|Karius Inc: Stocks/Bonds Sivan Bercovici, PhD, Karius: Stocks/Bonds Bradley A. Perkins, MD, Karius, Inc: Stocks/Bonds Timothy A. Blauwkamp, PhD, Karius: Board Member|Karius: Ownership Interest Vance G. Fowler, MD, MHS, Amphliphi Biosciences, Integrated Biotherapeutics; C3J, Armata, Valanbio; Akagera, Aridis, Roche, Astra Zeneca: Advisor/Consultant|Genentech, Regeneron, Deep Blue, Basilea, Janssen;: Grant/Research Support|Infectious Diseases Society of America: Honoraria|MedImmune, Allergan, Pfizer, Advanced Liquid Logics, Theravance, Novartis, Merck; Medical Biosurfaces; Locus; Affinergy; Contrafect; Karius;: Grant/Research Support|Novartis, Debiopharm, Genentech, Achaogen, Affinium, Medicines Co., MedImmune, Bayer, Basilea, Affinergy, Janssen, Contrafect, Regeneron, Destiny,: Advisor/Consultant|Sepsis diagnostic: Patent pending|UpToDate: Royalties|Valanbio and ArcBio: Stock Options Thomas L. Holland, MD, Aridis: Advisor/Consultant|Basilea Pharmaceutica: Advisor/Consultant|Karius: Advisor/Consultant|Lysovant: Advisor/Consultant Stephen P. Bergin, MD, Karius, Inc.: Grant/Research Support

Abstract Background Limited data exist on population-based risks and risk ratios (RRs) of coronavirus disease 2019 (COVID-19)–associated hospitalizations and clinical outcomes stratified by age and race/ethnicity. Methods Using data from electronic health records and claims from 4 US health systems for the period March 2020–March 2021, we calculated risk and RR by age and race/ethnicity for COVID-19–associated hospitalizations and clinical outcomes among adults (≥18 years). COVID-19–associated hospitalizations were defined based on COVID-19 discharge codes or a positive severe acute respiratory syndrome coronavirus 2 result. Proportions of acute exacerbations of underlying conditions were estimated among hospitalized patients with select underlying conditions, stratified by age and race/ethnicity. Results Among 2.6 million adults included in the patient cohort, 6879 had COVID-19–associated hospitalizations during March 2020–March 2021 (risk: 264 per 100 000 population). Compared with younger, non-Hispanic White adults, non-Hispanic Black and Hispanic adults aged ≥65 years had the highest hospitalization risk ratios (RR, 8.6; 95% CI, 7.6–9.9; and RR, 9.3; 95% CI, 8.5–10.3, respectively). Among hospitalized adults with COVID-19 and renal disease or cardiovascular disease, the highest proportion of acute renal failure (55.5%) or congestive heart failure (43.9%) occurred in older, non-Hispanic Black patients. Among hospitalized adults with chronic lung disease or asthma, the highest proportion of respiratory failure (62.9%) or asthma exacerbation (66.7%) occurred in older, Hispanic patients. Conclusions During the first year of the US COVID-19 pandemic in this cohort, older non-Hispanic Black and Hispanic adults had the highest relative risks of COVID-19–associated hospitalization and adverse outcomes and, among those with select underlying conditions, the highest occurrences of acute exacerbations of underlying conditions.

Previous infection with SARS-CoV-2 (the virus that causes COVID-19) or COVID-19 vaccination can provide immunity and protection from subsequent SARS-CoV-2 infection and illness. CDC used data from the VISION Network* to examine hospitalizations in adults with COVID-19-like illness and compared the odds of receiving a positive SARS-CoV-2 test result, and thus having laboratory-confirmed COVID-19, between unvaccinated patients with a previous SARS-CoV-2 infection occurring 90-179 days before COVID-19-like illness hospitalization, and patients who were fully vaccinated with an mRNA COVID-19 vaccine 90-179 days before hospitalization with no previous documented SARS-CoV-2 infection. Hospitalized adults aged ≥18 years with COVID-19-like illness were included if they had received testing at least twice: once associated with a COVID-19-like illness hospitalization during January-September 2021 and at least once earlier (since February 1, 2020, and ≥14 days before that hospitalization). Among COVID-19-like illness hospitalizations in persons whose previous infection or vaccination occurred 90-179 days earlier, the odds of laboratory-confirmed COVID-19 (adjusted for sociodemographic and health characteristics) among unvaccinated, previously infected adults were higher than the odds among fully vaccinated recipients of an mRNA COVID-19 vaccine with no previous documented infection (adjusted odds ratio [aOR] = 5.49; 95% confidence interval [CI] = 2.75-10.99). These findings suggest that among hospitalized adults with COVID-19-like illness whose previous infection or vaccination occurred 90-179 days earlier, vaccine-induced immunity was more protective than infection-induced immunity against laboratory-confirmed COVID-19. All eligible persons should be vaccinated against COVID-19 as soon as possible, including unvaccinated persons previously infected with SARS-CoV-2.

BACKGROUND:There are limited data on the effectiveness of the vaccines against symptomatic coronavirus disease 2019 (Covid-19) currently authorized in the United States with respect to hospitalization, admission to an intensive care unit (ICU), or ambulatory care in an emergency department or urgent care clinic.METHODS:We conducted a study involving adults (≥50 years of age) with Covid-19-like illness who underwent molecular testing for severe acute respiratory syndrome coronavirus 2 (SARS-CoV-2). We assessed 41,552 admissions to 187 hospitals and 21,522 visits to 221 emergency departments or urgent care clinics during the period from January 1 through June 22, 2021, in multiple states. The patients' vaccination status was documented in electronic health records and immunization registries. We used a test-negative design to estimate vaccine effectiveness by comparing the odds of a positive test for SARS-CoV-2 infection among vaccinated patients with those among unvaccinated patients. Vaccine effectiveness was adjusted with weights based on propensity-for-vaccination scores and according to age, geographic region, calendar time (days from January 1, 2021, to the index date for each medical visit), and local virus circulation.RESULTS:The effectiveness of full messenger RNA (mRNA) vaccination (≥14 days after the second dose) was 89% (95% confidence interval [CI], 87 to 91) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization, 90% (95% CI, 86 to 93) against infection leading to an ICU admission, and 91% (95% CI, 89 to 93) against infection leading to an emergency department or urgent care clinic visit. The effectiveness of full vaccination with respect to a Covid-19-associated hospitalization or emergency department or urgent care clinic visit was similar with the BNT162b2 and mRNA-1273 vaccines and ranged from 81% to 95% among adults 85 years of age or older, persons with chronic medical conditions, and Black or Hispanic adults. The effectiveness of the Ad26.COV2.S vaccine was 68% (95% CI, 50 to 79) against laboratory-confirmed SARS-CoV-2 infection leading to hospitalization and 73% (95% CI, 59 to 82) against infection leading to an emergency department or urgent care clinic visit.CONCLUSIONS:Covid-19 vaccines in the United States were highly effective against SARS-CoV-2 infection requiring hospitalization, ICU admission, or an emergency department or urgent care clinic visit. This vaccine effectiveness extended to populations that are disproportionately affected by SARS-CoV-2 infection. (Funded by the Centers for Disease Control and Prevention.).

Abstract Background Evaluate an indication‐based clinical decision support tool to improve antibiotic prescribing in the emergency department. Methods Encounters where an antibiotic was prescribed between January 2015 and October 2017 were analyzed before and after the introduction of a clinical decision support tool to improve clinicians’ selection of a guideline‐approved antibiotic based on clinical indication. Evaluation was conducted on a pre‐defined subset of conditions that included skin and soft tissue infections, respiratory infections, and urinary infections. The primary outcome was ordering of a guideline‐approved antibiotic prescription at the drug and duration of therapy level. A mixed model following a binomial distribution with a logit link was used to model the difference in proportions of guideline‐approved prescriptions before and after the intervention. Results For conditions evaluated, selection rate of a guideline‐approved antibiotic for a given indication improved from 67.1% to 72.2% (P < 0.001). When duration of therapy is included as a criterion, selection of a guideline‐approved antibiotic was lower and improved from 24.7% to 31.4% (P < 0.001), highlighting that duration of therapy is often missing at the time of prescribing. The most substantial improvements were seen for pneumonia and pyelonephritis with an increase from 87.9% to 97.5% and 62.8% to 82.6%, respectively. Other significant improvements were seen for abscess, cellulitis, and urinary tract infections. Conclusion Antibiotic prescribing can be improved both at the drug and duration of therapy level using a non‐interruptive and indication based‐clinical decision support approach. Future research and quality improvement efforts are needed to incorporate duration of therapy guidelines into the antibiotic prescribing process.

We present a case of Cryptococcus neoformans pericarditis in a cardiac transplant recipient. This article reviews the diagnosis, treatment, and complications of cryptococcosis specifically in transplant patients. While pericarditis is a rare manifestation of Cryptococcus infection, this case highlights that cryptococcosis should be considered in the differential diagnosis for solid organ transplant and immunocompromised patients presenting with pericardial effusions.

Abstract Introduction Patients with 90% or greater total body surface area (TBSA) burns of face many unique challenges, including prolonged open wounds and antibiotic use. Furthermore, increased antibiotic use can be associated with increased antibiotic resistance. Despite the commonality, the relationship between prolonged wound closure (months) combined with prolonged duration of antibiotic use (months) has not been fully explored. The specific aim of this study was to examine the evolution of burned patients’ microbiome over time in association with wound healing and antibiotic use. Methods We conducted a retrospective review of all patients admitted to our ABA-verified burn center from 2010-present with 90% TBSA or greater burns who survived to discharge. Demographic data, length of stay, percentage monthly wound closure (including donor sites), microbial culture data of bacteria, yeast, fungus, and mold (YFM), antibiotic susceptibilities, and systemic antimicrobial agents administered were recorded. Statistical analysis was performed using Pearson correlation coefficient. Results Two patients met inclusion criteria. Patient A (PtA), a 36 year old (yo) female with 95% TBSA burns and Patient B (PtB), a 45 yo male with 90% TBSA burns. Patients spent a combined 766 days (PtA 425, PtB 341) as inpatients. 347 separate positive cultures were analyzed, 180 of which were bacterial. 15 distinct species of bacteria were cultured (8 PtA, 9 PtB), along with 4 subtypes of Pseudomonas aeruginosa, and 9 distinct YFM (6 PtA, 6 PtB). Increasing antibiotic resistance was found in 57% (PtA) and 71% (PtB) of bacterial species. Pseudomonas was the most commonly isolated organism in 65% (n=118) of cultures. The relationships between percent wound closure, daily antibiotic use, and Pseudomonas antibiotic resistance are shown in the Graph below. There was a strong correlation between wound closure of >50% with decreased amount of antibiotics used per day (PtA 0.83, PtB 0.86) and decreasing % of Pseudomonas antibiotic resistance (PtA 0.66, PtB 0.8). Conclusions Antibiotic resistance increases over time and efforts should be taken to decrease number of antibiotics administered. As wound closure passes a certain threshold, the number of antibiotics needed decreases, and Pseudomonas antibiotic resistance appears to decrease as well. Applicability of Research to Practice Recognition of different environmental pressures for bacteria may point to changes in microbial resistance patterns and thus clinical management.

Abstract Background Up to 80% of cases of acute infectious gastroenteritis do not have an identifiable etiologic agent. Molecular syndromic diagnostic panels, such as the Biofire® Filmarray® gastrointestinal (GI) panel, can improve pathogen detection, including frequent causes of community-onset diarrhea. There are little data about the real-world use and test characteristics of the GI panel in the clinical setting. The objective of this study was to evaluate the patterns of use and clinical utility of the GI panel. Methods We conducted a retrospective cohort study of adults (age >18 years) admitted to the University of Colorado Hospital for whom a GI Panel was ordered from October 1, 2015 to August 31, 2017. Primary outcomes included patient demographics and co-morbidities, time since admission to test order, and cumulative test results. Descriptive statistics were utilized to summarize the frequencies of the primary outcome measures. Results 1684 panels were ordered and completed during the study period compared with 1379 stand-alone C. difficile PCRs. Seventeen of the 22 components of the panel had been validated by our lab prior to the study period; therefore, results were only available for these pathogens. Most GI panels (78%) were ordered in the first 48 hours of admission, with 6% ordered between 48 and 72 hours after admission, and 16% >72 hours after admission. The GI panel yielded an organism 34% of the time. The most frequently identified organism was C. difficile (18.5%) followed by Norovirus (5.2%) and Enteropathogenic E. coli (5.1%). Conclusion Over a 2-year period at a University hospital, the GI panel only had a positive result in 20% of patients tested. Although most of the tests were ordered in the first 48 hours after admission, 22% were ordered after 48 hours, after which etiologies of hospital-onset diarrhea are expected to be more common. Among all GI Panel tests ordered, C. difficile was the most common organism identified, followed by Norovirus. Each of these organisms has an accurate and less costly alternative test. Stand-alone testing for C. difficile and Norovirus should be considered prior to the GI Panel for patients admitted to the hospital, particularly when admitted >48 hours. Disclosures All authors: No reported disclosures.

Background. Vancomycin is the most commonly administered antibiotic in hospitalized patients, but optimal exposure targets remain controversial. To clarify the therapeutic exposure range, this study evaluated the association between vancomycin exposure and outcomes in patients with methicillin-resistant Staphylococcus aureus (MRSA) bacteremia. Methods. This was a prospective, multicenter (n = 14), observational study of 265 hospitalized adults with MRSA bacteremia treated with vancomycin. The primary outcome was treatment failure (TF), defined as 30-day mortality or persistent bacteremia >= 7 days. Secondary outcomes included acute kidney injury (AKI). The study was powered to compare TF between patients who achieved or did not achieve day 2 area under the curve to minimum inhibitory concentration (AUC/MIC) thresholds previously found to be associated with lower incidences of TF. The thresholds, analyzed separately as co-primary endpoints, were AUC/MIC by broth microdilution >= 650 and AUC/MIC by Etest >= 320. Results. Treatment failure and AKI occurred in 18% and 26% of patients, respectively. Achievement of the prespecified day 2 AUC/MIC thresholds was not associated with less TF. Alternative day 2 AUC/MIC thresholds associated with lower TF risks were not identified. A relationship between the day 2 AUC and AKI was observed. Patients with day 2 AUC <= 515 experienced the best global outcomes (no TF and no AKI). Conclusions. Higher vancomycin exposures did not confer a lower TF risk but were associated with more AKI. The findings suggest that vancomycin dosing should be guided by the AUC and day 2 AUCs should be <= 515. As few patients had day 2 AUCs <400, further study is needed to define the lower bound of the therapeutic range.

Abstract Background C. difficile infection (CDI) remains a significant cause of morbidity and mortality. The most appropriate clinical scenario for CDI testing is unclear. The IDSA/SHEA guideline recommends testing patients with unexplained new-onset ≥3 stools in 24 hours. This study sought to evaluate clinical factors associated with a positive C. difficile PCR test. Methods We conducted a retrospective cohort study of adults (age >18 years old) admitted to the University of Colorado Hospital for whom a C. difficile PCR, either as a standalone test or part of the Biofire® Filmarray® Gastrointestinal Panel (GI Panel), was ordered between October 1, 2015 and August 31, 2017. Data collected included time since admission to test order, hospital length of stay, history of CDI, antibiotic use in the past 90 days, clinical presentation in the 24 hours preceding test order (fever, leukocytosis, number of stools), and laxative or antibiotic administration within 24 hours of test order. Multivariate logistic regression was used to evaluate the association of the above variables with having a positive C. difficile PCR test. If multiple tests were ordered during a single hospital encounter, only the first test was included in our analysis. Results 3,070 tests were performed; of these, 72% were ordered in the first 72 hours of admission. Overall, 19% of tests were positive. After adjusting for clinical variables, patients with a prior history of C. difficile or who had received antibiotics in the past 24 hours were significantly more likely to have a positive test [OR 2.2 95% CI (1.54, 3.18) P < 0.0001] and [OR 16 95% CI (8.22, 31.41) P < 0.0001], respectively. Patients who used laxatives were significantly less likely to have a positive test [OR 0.75 95% CI (0.61, 0.91) P = 0.004]. The number of stools and presence of fever or leukocytosis were not significantly associated with a positive test. Conclusion Prior history of C. difficile and antibiotics use was highly associated with a positive C. difficile test, while laxatives use was associated with a negative test. The number of stools was not significantly associated with a positive C. difficile test, suggesting this may be less important clinical factor than previously believed; however, restricting testing in patients receiving laxatives is likely warranted. Disclosures All authors: No reported disclosures.