Dimitri M Drekonja, Aasma Shaukat, Yuan Huang, Jane H Zhang, Andrew R Reinink, Sean Nugent, Jason A Dominitz, Anne Davis-Karim, Dale N Gerding, Tassos C Kyriakides
Background Clostridioides difficile infection (CDI) is the most common cause of healthcare–associated infections in US hospitals with 15%-30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplantation (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment. Methods Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or ≥2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for ≥2 days with or without laboratory confirmation of C. difficile, or death within 56 days. Results The study was stopped due to futility after meeting pre-specified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference 3.0%; 95% CI [-11.7%, 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events. Conclusions FMT therapy vs. placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.
{"title":"A randomized controlled trial of efficacy and safety of Fecal Microbiota Transplant for preventing recurrent Clostridioides difficile infection","authors":"Dimitri M Drekonja, Aasma Shaukat, Yuan Huang, Jane H Zhang, Andrew R Reinink, Sean Nugent, Jason A Dominitz, Anne Davis-Karim, Dale N Gerding, Tassos C Kyriakides","doi":"10.1093/cid/ciae467","DOIUrl":"https://doi.org/10.1093/cid/ciae467","url":null,"abstract":"Background Clostridioides difficile infection (CDI) is the most common cause of healthcare–associated infections in US hospitals with 15%-30% of patients experiencing recurrence. The aim of our randomized, double-blind clinical trial was to assess the efficacy of capsule-delivered fecal microbiota transplantation (FMT) versus placebo in reducing recurrent diarrhea and CDI recurrence. The secondary aim was FMT safety assessment. Methods Between 2018 and 2022, Veterans across the Veterans Health Administration system with recurrent CDI who responded to antibiotic treatment were randomized in a 1:1 ratio to oral FMT or placebo capsules. Randomization was stratified by number of prior CDI recurrences (1 or ≥2). The primary endpoint was clinical recurrence by day 56, defined as >3 unformed stools daily for ≥2 days with or without laboratory confirmation of C. difficile, or death within 56 days. Results The study was stopped due to futility after meeting pre-specified criteria. Of 153 participants (76 FMT, 77 placebo) with an average age of 66.5 years, 25 participants (32.9%) in the FMT arm and 23 (29.9%) in the placebo arm experienced the primary endpoint of diarrhea and possible or definite CDI recurrence or death within 56 days of capsule administration (absolute difference 3.0%; 95% CI [-11.7%, 17.7%]). Stratification by number of recurrences revealed no statistically significant differences. There were no clinically important differences in adverse events. Conclusions FMT therapy vs. placebo did not reduce CDI recurrence or death at 56 days. There were no meaningful differences in adverse events between treatment groups.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-09-14","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233264","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jessica Leung, Naeemah A Munir, Adria D Mathis, Thomas D Filardo, Paul A Rota, David E Sugerman, Sun B Sowers, Sara Mercader, Stephen N Crooke, Paul A Gastañaduy
Background Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. Methods We included U.S. measles cases reported from 2001–2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Results Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged <5, 5–19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5–19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Discussion Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.
{"title":"The Effects of Vaccination Status and Age on Clinical Characteristics and Severity of Measles Cases in the United States in the Post-Elimination Era, 2001-2022","authors":"Jessica Leung, Naeemah A Munir, Adria D Mathis, Thomas D Filardo, Paul A Rota, David E Sugerman, Sun B Sowers, Sara Mercader, Stephen N Crooke, Paul A Gastañaduy","doi":"10.1093/cid/ciae470","DOIUrl":"https://doi.org/10.1093/cid/ciae470","url":null,"abstract":"Background Despite high vaccine-effectiveness, wild-type measles can occur in previously vaccinated persons. We compared the clinical presentation and disease severity of measles by vaccination status and age in the post-elimination era in the United States. Methods We included U.S. measles cases reported from 2001–2022. Breakthrough measles was defined as cases with ≥1 documented dose of measles-containing vaccine, classic measles as the presence of rash, fever, and ≥1 symptoms (cough, coryza, or conjunctivitis), and severe disease as the presence of pneumonia, encephalitis, hospitalization, or death. Vaccinated cases with low and high avidity IgG were classified as primary (PVF) and secondary (SVF) vaccine failures, respectively. Results Among 4,056 confirmed measles cases, 2,799 (69%) were unvaccinated, 475 (12%) were breakthrough infections, and 782 (19%) had unknown vaccination; 1,526 (38%), 1,174 (29%), and 1,355 (33%) were aged &lt;5, 5–19, and ≥20 years, respectively. We observed a general decline in classic presentation and severe disease with an increase in the number of doses, and less complications among children aged 5–19 years compared to other age-groups. Among 93 breakthrough cases with avidity results, 11 (12%) and 76 (82%) were classified as PVF and SVF, respectively, with a higher proportion of PVFs having a classic measles presentation and severe disease than SVFs. Discussion Breakthrough measles cases tended to have milder disease with less complications. A small proportion of breakthrough infections were due to PVF than SVF. It is critical to maintain high MMR vaccination coverage in the United States to prevent serious measles illnesses.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233266","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
{"title":"Déjà vu: Unanswered Questions about Fecal Microbiota Transplantation for Recurrent Clostridioides difficile Infection.","authors":"Susan M Poutanen,Susy S Hota","doi":"10.1093/cid/ciae468","DOIUrl":"https://doi.org/10.1093/cid/ciae468","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-09-13","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233265","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Tomas O Jensen, Katrina Harper, Shaili Gupta, Sean T Liu, Nila J Dharan, Jason V Baker, Sarah L Pett, Kathryn Shaw-Saliba, Aliasgar Esmail, Minh Q Ho, Eyad Almasri, Robin L Dewar, Jens Lundgren, David M Vock
Background Extrapulmonary complications (EPCs) are common in patients hospitalized for COVID-19, but data on their clinical consequences and association with viral replication and systemic viral dissemination is lacking. Methods Patients hospitalized for COVID-19 and enrolled in the TICO (Therapeutics for Inpatients with COVID-19) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90. We analyzed the association between baseline viral burden (plasma nucleocapsid antigen [N-Ag] and upper airway viral load [VL]) and EPCs, adjusting for other baseline factors. Results 2,625 trial participants were included in the study. The median age was 57 years (IQR 46-68), 57.7% were male, and 537 (20.5%) had at least one EPC. EPCs were associated with higher day-90 all-cause mortality (HR 9.6, 95% CI 7.3, 12.7) after adjustment for other risk factors. The risk of EPCs increased with increasing baseline plasma N-Ag (HR 1.21 per log10 ng/L increase, 95% CI 1.09, 1.34), and upper airway VL (HR 1.12 per log10 copies/mL increase, 95% CI 1.04, 1.19), after adjusting for comorbidities, disease severity, inflammatory markers, and other baseline factors. Trial treatment allocation had no effect on EPC risk. Conclusions Systemic viral dissemination as evidenced by high plasma N-Ag and high respiratory viral burden are associated with development of EPCs in COVID-19, which in turn are associated with higher 90-day mortality.
{"title":"Impact of baseline SARS-CoV-2 load in plasma and upper airways on the incidence of acute extrapulmonary complications of COVID-19: a multicentric, prospective, cohort study","authors":"Tomas O Jensen, Katrina Harper, Shaili Gupta, Sean T Liu, Nila J Dharan, Jason V Baker, Sarah L Pett, Kathryn Shaw-Saliba, Aliasgar Esmail, Minh Q Ho, Eyad Almasri, Robin L Dewar, Jens Lundgren, David M Vock","doi":"10.1093/cid/ciae469","DOIUrl":"https://doi.org/10.1093/cid/ciae469","url":null,"abstract":"Background Extrapulmonary complications (EPCs) are common in patients hospitalized for COVID-19, but data on their clinical consequences and association with viral replication and systemic viral dissemination is lacking. Methods Patients hospitalized for COVID-19 and enrolled in the TICO (Therapeutics for Inpatients with COVID-19) platform trial at 114 international sites between August 2020 and November 2021 were included in a prospective cohort study. We categorized EPCs into 39 event types within 9 categories and estimated their frequency through day 28 and their association with clinical outcomes through day 90. We analyzed the association between baseline viral burden (plasma nucleocapsid antigen [N-Ag] and upper airway viral load [VL]) and EPCs, adjusting for other baseline factors. Results 2,625 trial participants were included in the study. The median age was 57 years (IQR 46-68), 57.7% were male, and 537 (20.5%) had at least one EPC. EPCs were associated with higher day-90 all-cause mortality (HR 9.6, 95% CI 7.3, 12.7) after adjustment for other risk factors. The risk of EPCs increased with increasing baseline plasma N-Ag (HR 1.21 per log10 ng/L increase, 95% CI 1.09, 1.34), and upper airway VL (HR 1.12 per log10 copies/mL increase, 95% CI 1.04, 1.19), after adjusting for comorbidities, disease severity, inflammatory markers, and other baseline factors. Trial treatment allocation had no effect on EPC risk. Conclusions Systemic viral dissemination as evidenced by high plasma N-Ag and high respiratory viral burden are associated with development of EPCs in COVID-19, which in turn are associated with higher 90-day mortality.","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":11.8,"publicationDate":"2024-09-12","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142233267","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Stanley A Plotkin, James M Robinson, Joseph R A Fitchett, Edward Gershburg
Vaccines based on mRNA technology have been tremendously successful, but their properties are not necessarily ideal for all pathogens. There is a risk that concentration on that technology alone for new vaccine development will ignore older technologies that have properties giving broader and more persistent protection.
{"title":"Vaccine Development Should Be Polytheistic, Not Monotheistic.","authors":"Stanley A Plotkin, James M Robinson, Joseph R A Fitchett, Edward Gershburg","doi":"10.1093/cid/ciae460","DOIUrl":"https://doi.org/10.1093/cid/ciae460","url":null,"abstract":"<p><p>Vaccines based on mRNA technology have been tremendously successful, but their properties are not necessarily ideal for all pathogens. There is a risk that concentration on that technology alone for new vaccine development will ignore older technologies that have properties giving broader and more persistent protection.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143038","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sheeba Santhini Manoharan-Basil, Thibaut Vanbaelen, Chris Kenyon
{"title":"Adverse impact of azithromycin on the rectal microbiome.","authors":"Sheeba Santhini Manoharan-Basil, Thibaut Vanbaelen, Chris Kenyon","doi":"10.1093/cid/ciae452","DOIUrl":"https://doi.org/10.1093/cid/ciae452","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142143037","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Pierre Danneels, Jean-François Hamel, Vincent Dubée
{"title":"Adjunctive Therapy in Enterococcus faecalis Endocarditis Treatment: Maybe Less is Not Enough.","authors":"Pierre Danneels, Jean-François Hamel, Vincent Dubée","doi":"10.1093/cid/ciae459","DOIUrl":"https://doi.org/10.1093/cid/ciae459","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-06","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139517","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Marva Seifert, Donald G Catanzaro, Michael Gracia, Naomi Hillery, Sabira Tahseen, Faisal Masood, Alamdar Hussain, Uzma Majeed, Rebecca E Coleman, Rehan R Syed, Antonino Catanzaro, Timothy Rodwell
Background: An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.
Methods: A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24).
Results: A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis.
Conclusions: While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.
{"title":"Prospective exploratory evaluation of Cepheid Xpert Mycobacterium tuberculosis host response cartridge: a focus on adolescents and young adults.","authors":"Marva Seifert, Donald G Catanzaro, Michael Gracia, Naomi Hillery, Sabira Tahseen, Faisal Masood, Alamdar Hussain, Uzma Majeed, Rebecca E Coleman, Rehan R Syed, Antonino Catanzaro, Timothy Rodwell","doi":"10.1093/cid/ciae461","DOIUrl":"https://doi.org/10.1093/cid/ciae461","url":null,"abstract":"<p><strong>Background: </strong>An accurate, rapid, non-sputum-based triage test for diagnosing tuberculosis (TB) is needed.</p><p><strong>Methods: </strong>A prospective evaluation of the Xpert-MTB-HR cartridge, a prototype blood-based host-response mRNA signature assay, among individuals presenting with TB-like symptoms was performed in Pakistan and results were compared to three reference standards: Xpert MTB/RIF Ultra, bacteriological confirmation (Xpert MTB/RIF Ultra and/or culture positivity), and composite clinical diagnosis (clinician diagnosis, treatment initiation, Xpert MTB/RIF Ultra, and/or culture positivity). Analyses were conducted both for the entire study cohort and separately in the adolescent and young adult cohort (ages 10-24).</p><p><strong>Results: </strong>A total of 497 participants, ages 6-83, returned valid Xpert-MTB-HR results. When a diagnostic threshold was set for a sensitivity of >90%, specificity was 32% (95%CI 28-37) when compared to Xpert MTB/RIF Ultra, 29% (95%CI 25-34) when compared to a bacteriological confirmation, and 22% (95%CI 18-26) when compared to a composite clinical diagnosis. However, when evaluating only the adolescent and young adult cohort with a diagnostic threshold set for sensitivity of >90%, specificity was 82% (95%CI 74-89) when compared to Xpert MTB/RIF Ultra, 84% (95%CI 75-90) when compared to a bacteriological confirmation, and 54% (95%CI 44-64) when compared to a composite clinical diagnosis.</p><p><strong>Conclusions: </strong>While the Xpert-MTB-HR does not meet World Health Organization minimum criteria in the general population, in our study it does meet the minimum sensitivity and specificity requirements for a non-sputum-based triage test among adolescents and young adults when compared to Xpert MTB/RIF Ultra or bacteriological confirmation.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-09-05","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142132057","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":1,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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