Browsing by Author "Silverman, Michael"

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    Correction to: Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI
    (2024-08-30) Kraft, Colleen S.; Sims, Matthew; Silverman, Michael; Louie, Thomas J.; Feuerstadt, Paul; Huang, Edward S.; Khanna, Sahil; Berenson, Charles S.; Wang, Elaine E. L.; Cohen, Stuart H.; Korman, Louis; Lee, Christine; Kelly, Colleen R.; Odio, Alberto; Cook, Paul P.; Lashner, Bret; Ramesh, Mayur; Kumar, Princy; De, Ananya; Memisoglu, Asli; Lombardi, David A.; Hasson, Brooke R.; McGovern, Barbara H.; von Moltke, Lisa; Pardi, Darrell S.
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    Integrated Safety and Efficacy Analyses of Phase 3 Trials of a Microbiome Therapeutic for Recurrent CDI
    (2024-06-28) Kraft, Colleen S.; Sims, Matthew; Silverman, Michael; Louie, Thomas J.; Feuerstadt, Paul; Huang, Edward S.; Khanna, Sahil; Berenson, Charles S.; Wang, Elaine E. L.; Cohen, Stuart H.; Korman, Louis; Lee, Christine; Kelly, Colleen R.; Odio, Alberto; Cook, Paul P.; Lashner, Bret; Ramesh, Mayur; Kumar, Princy; De, Ananya; Memisoglu, Asli; Lombardi, David A.; Hasson, Brooke R.; McGovern, Barbara H.; von Moltke, Lisa; Pardi, Darrell S.
    Abstract Introduction Recurrent Clostridioides difficile infection (rCDI) often occurs after standard-of-care antibiotics. VOWST oral spores (VOS, previously SER-109), an FDA-approved orally administered microbiome therapeutic, is indicated to prevent rCDI following antibiotics for rCDI. Objective, Design, and Patients To evaluate safety and efficacy of VOS from two phase 3 trials, (randomized, placebo-controlled [ECOSPOR III: NCT03183128] and open-label, single arm [ECOSPOR IV: NCT03183141]) of 349 adults with rCDI and prevalent comorbidities. Methods VOS or placebo [ECOSPOR III only] (4 capsules once daily for 3 days). Integrated analysis of treatment-emergent adverse events (TEAEs) collected through week 8; serious TEAEs and TEAEs of special interest collected through week 24; and rates of rCDI (toxin-positive diarrhea requiring treatment) evaluated through weeks 8 and 24. Results TEAEs were mostly mild or moderate and gastrointestinal. Most common treatment-related TEAEs were flatulence, abdominal pain and distension, fatigue, and diarrhea. There were 11 deaths (3.2%) and 48 patients (13.8%) with serious TEAEs, none treatment-related. The rCDI rate through week 8 was 9.5% (95% CI 6.6–13.0) and remained low through 24 weeks (15.2%; 95% CI 11.6–19.4). Safety and rCDI rates were consistent across subgroups including age, renal impairment/failure, diabetes, and immunocompromise/immunosuppression. Conclusions VOS was well tolerated and rates of rCDI remained low through week 24 including in those with comorbidities. These data support the potential benefit of VOS following antibiotics to prevent recurrence in high-risk patients. Trial Registration ClinicalTrials.gov identifier, NCT03183128 and NCT03183141.
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    Quality of antibiotic prescribing for pediatric community-acquired Pneumonia in outpatient care
    (2023-10-28) Saatchi, Ariana; Haverkate, Manon R.; Reid, Jennifer N.; Shariff, Salimah Z.; Povitz, Marcus; Patrick, David M.; Silverman, Michael; Morris, Andrew M.; McCormack, James; Marra, Fawziah
    Abstract Background Antibiotics remain the primary treatment for community acquired pneumonia (CAP), however rising rates of antimicrobial resistance may jeopardize their future efficacy. With higher rates of disease reported in the youngest populations, effective treatment courses for pediatric pneumonia are of paramount importance. This study is the first to examine the quality of pediatric antibiotic use by agent, dose and duration. Methods A retrospective cohort study included all outpatient/primary care physician visits for pediatric CAP (aged < 19 years) between January 1 2014 to December 31 2018. Relevant practice guidelines were identified, and treatment recommendations extracted. Amoxicillin was the primary first-line agent for pediatric CAP. Categories of prescribing included: guideline adherent, effective but unnecessary (excess dose and/or duration), under treatment (insufficient dose and/or duration), and not recommended. Proportions of attributable-antibiotic use were examined by prescribing category, and then stratified by age and sex. Result(s) A total of 42,452 episodes of pediatric CAP were identified. Of those, 31,347 (76%) resulted in an antibiotic prescription. Amoxicillin accounted for 51% of all prescriptions. Overall, 27% of prescribing was fully guideline adherent, 19% effective but unnecessary, 10% under treatment, and 44% not recommended by agent. Excessive duration was the hallmark of effective but unnecessary prescribing (97%) Macrolides accounted for the majority on non-first line agent use, with only 32% of not recommended prescribing preceded by a previous course of antibiotics. Conclusion(s) This study is the first in Canada to examine prescribing quality for pediatric CAP by agent, dose and duration. Utilizing first-line agents, and shorter-course treatments are targets for stewardship.