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Background: Community-acquired pneumonia (CAP) is a significant public health concern and a leading cause of hospitalization and inpatient antimicrobial use in the USA. However, determining the etiologic pathogen is challenging because traditional culture methods are slow and insensitive, leading to prolonged empiric therapy with extended-spectrum antibiotics (ESA) that contributes to increased hospital length of stay, and antimicrobial resistance. Two potential ways to reduce the exposure to ESA are (a) rapid diagnostic assays that can provide accurate results within hours, obviating the need for empiric therapy, and (b) de-escalation following negative bacterial cultures in clinically stable patients., Methods: We will conduct a large pragmatic 2 × 2 factorial cluster-randomized controlled trial across 12 hospitals in the Cleveland Clinic Health System that will test these two approaches to reducing the use of ESA in adult patients (age ≥ 18 years) with CAP. We will enroll over 12,000 patients and evaluate the independent and combined effects of routine use of rapid diagnostic testing at admission and pharmacist-led de-escalation after 48 h for clinically stable patients with negative cultures vs usual care. We hypothesize that both approaches will reduce days on ESA. Our primary outcome is the duration of exposure to ESA therapy, a key driver of antimicrobial resistance. Secondary outcomes include detection of respiratory viruses, treatment with anti-viral medications, positive pneumococcal urinary antigen test, de-escalation by 72 h from admission, re-escalation to ESA after de-escalation, total duration of any antibiotic, 14-day in-hospital mortality, intensive care unit transfer after admission, healthcare-associated C. difficile infection, acute kidney injury, total inpatient cost, and hospital length-of-stay., Discussion: Our study aims to determine whether identifying an etiological agent early and pharmacist-led de-escalation (calling attention to negative cultures) can safely reduce the use of ESA in patients with CAP. If successful, our findings should lead to better antimicrobial stewardship, as well as improved patient outcomes and reduced healthcare costs. Our findings may also inform clinical guidelines on the optimal management of CAP., Trial Registration: ClinicalTrials.gov NCT05568654 . Registered on October 4, 2022., (© 2023. BioMed Central Ltd., part of Springer Nature.)

Background: Community-acquired pneumonia (CAP) is a leading cause of hospital admissions and antimicrobial use. Clinical practice guidelines recommend switching from intravenous (IV) to oral antibiotics once patients are clinically stable., Methods: We conducted a retrospective cohort study of adults admitted with CAP and initially treated with IV antibiotics at 642 US hospitals from 2010 through 2015. Switching was defined as discontinuation of IV and initiation of oral antibiotics without interrupting therapy. Patients switched by hospital day 3 were considered early switchers. We compared length of stay (LOS), in-hospital 14-day mortality, late deterioration (intensive care unit [ICU] transfer), and hospital costs between early switchers and others, controlling for hospital characteristics, patient demographics, comorbidities, initial treatments, and predicted mortality., Results: Of 378 041 CAP patients, 21 784 (6%) were switched early, most frequently to fluoroquinolones. Patients switched early had fewer days on IV antibiotics, shorter duration of inpatient antibiotic treatment, shorter LOS, and lower hospitalization costs, but no significant excesses in 14-day in-hospital mortality or late ICU admission. Patients at a higher mortality risk were less likely to be switched. However, even in hospitals with relatively high switch rates, <15% of very low-risk patients were switched early., Conclusions: Although early switching was not associated with worse outcomes and was associated with shorter LOS and fewer days on antibiotics, it occurred infrequently. Even in hospitals with high switch rates, <15% of very low-risk patients were switched early. Our findings suggest that many more patients could be switched early without compromising outcomes., Competing Interests: Conflict of interest. A. D. reports research funding (to institution) from the Clorox Company, consultant fees from Merck, and grants or contracts to institution, unrelated to the current study, from Seres Therapeutics. M. K. reports royalties from UpToDate and grants or contracts to institution from the Centers for Disease Control and Prevention and the Agency for Healthcare Research and Quality. M. D. Z. reports research support from Tetraphase Pharmaceuticals, Astellas, Lungpacer, Merck, Spero, Medicines Co, Melinta, scPharma, Shionogi, and Pfizer; consulting fees from Paratek, Arasanis, Shionogi, Pfizer, Nabriva, scPharma, and Melinta; and stock or stock options from Johnson & Johnson. T. H. reports consulting fees from the Cerner Corporation. P. B. I. reports consulting fees from Colgate-Palmolive. S. H. reports a role with the Society for Health Epidemiology of America (councilor, board of trustees, volunteer; no compensation). All remaining authors: No reported conflicts of interest. All authors have submitted the ICMJE Form for Disclosure of Potential Conflicts of Interest. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed., (© The Author(s) 2023. Published by Oxford University Press on behalf of Infectious Diseases Society of America. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com.)

Background: Influenza is a leading cause of community-acquired pneumonia (CAP), and results of influenza tests can direct therapy. However, among adults hospitalized with CAP, little is known about the frequency and timing of influenza testing, treatment, and their associations with outcomes., Research Question: In patients with CAP, is testing for influenza associated with antiviral treatment and shorter antibiotic courses, and is early treatment associated with better clinical outcomes?, Study Design and Methods: This study included adults admitted with pneumonia in 2010 to 2015 to 179 US hospitals contributing to the Premier database. We assessed influenza testing and compared antimicrobial utilization and the outcomes of test-positive, test-negative, and untested patients. Associations of early antiviral treatment (oseltamivir) with 14-day in-hospital mortality, hospital length of stay, and cost were studied., Results: Among 166,268 patients with CAP, 38,703 (23.3%) were tested for influenza, of whom 11.5% tested positive. Testing increased from 15.4% to 35.6% from 2010 to 2015 and was 28.9% during flu season (October-May) vs 8.2% in June to September. Patients testing positive for influenza received antiviral agents more often and antibacterial agents less often and for shorter courses than patients testing negative (5.3 vs 6.4 days; P < .001). Influenza-positive patients receiving oseltamivir on hospital day 1 (n = 2,585) experienced lower 14-day in-hospital mortality (adjusted OR, 0.75; 95% CI, 0.59-0.96), lower costs (adjusted ratio of means, 0.88; 95% CI, 0.81-0.95), and shorter length of stay (adjusted ratio of means, 0.88; 95% CI, 0.84-0.93) vs patients receiving oseltamivir later or not at all (n = 1,742)., Interpretation: Even during flu season, most patients with CAP in this study went untested for influenza. A positive influenza test result was associated with antiviral treatment, and early treatment was associated with lower mortality, suggesting that more widespread testing might improve patient outcomes., (Copyright © 2022 American College of Chest Physicians. Published by Elsevier Inc. All rights reserved.)

Background: Acute kidney injury (AKI) is common among hospitalized patients with community-acquired pneumonia (CAP). We aimed to estimate and compare the risk of AKI for various antibiotic combinations in adults hospitalized for CAP., Methods: We conducted a retrospective cohort study of the Premier Healthcare Database containing all admissions for 660 US hospitals from 2010 to 2015. We included adults aged ≥18 years hospitalized with CAP and considered 6 different antibiotic combinations based on continuous use in the first 3 hospital days. The primary outcome was incident AKI, defined by ICD-9 codes 584.5-584-9. We evaluated associations of AKI with in-hospital mortality and length-of-stay. We excluded patients who were admitted directly to the intensive care unit, had AKI codes present on admission or had dialysis in the first 2 days. We used generalized linear mixed models with the hospital as a random effect and covariate adjustment for patient demographics, comorbidities, other treatments on day 0/1, and hospital characteristics., Results: The total sample included 449,535 patients, 3.15% of whom developed AKI. All other regimens but fluoroquinolones exhibited higher AKI odds than 3rd generation cephalosporin with or without macrolide. The combination of piperacillin/tazobactam and vancomycin with or without other antibiotics was associated with the highest AKI odds (OR = 1.89; 95% CI: 1.73-2.06). Patients with incident AKI had an increased odds of hospital mortality (OR = 6.37; 95% CI: 6.07-6.69) and longer length-of-stay (mean multiplier = 1.84; 95% CI: 1.82, 1.86)., Conclusion: Compared to 3rd generation cephalosporin with or without macrolide, piperacillin/tazobactam, vancomycin, and their combination were associated with higher odds of developing AKI, which in turn were associated with worse clinical outcomes.