Aurélien Dinh, Martin McNally, Emma D'Anglejan, Christel Mamona Kilu, Julie Lourtet, Rosemary Ho, Matthew Scarborough, Maria Dudareva, Gerald Jesuthasan, Cecile Ronde Oustau, Stéphane Klein, Laura Escolà-Vergé, Dolores Rodriguez Pardo, Pierre Delobel, Jaime Lora-Tamayo, Mikel Mancheño-Losa, Maria Luisa Sorlí Redó, José María Barbero Allende, Cédric Arvieux, Danguole Vaznaisiène, Thomas Bauer, Anne-Laure Roux, Latifa Noussair, Stéphane Corvec, Marta Fernández-Sampedro, Nicolò Rossi, Adrien Lemaignen, Mauro José Costa Salles, Taiana Cunha Ribeiro, Julien Mazet, Milène Sasso, Jean-Philippe Lavigne, Albert Sotto, Etienne Canouï, Éric Senneville, Pauline Thill, Olivier Lortholary, Fanny Lanternier, Laura Morata, Alex Soriano, Gérard Giordano, Camille Fourcade, Bernhard J H Franck, Jochen G Hofstätter, Clara Duran, Eric Bonnet
Background: Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI.
Methods: This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up.
Results: A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777).
Conclusions: Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.
{"title":"Prosthetic Joint Infections due to Candida Species: A Multicenter International Study.","authors":"Aurélien Dinh, Martin McNally, Emma D'Anglejan, Christel Mamona Kilu, Julie Lourtet, Rosemary Ho, Matthew Scarborough, Maria Dudareva, Gerald Jesuthasan, Cecile Ronde Oustau, Stéphane Klein, Laura Escolà-Vergé, Dolores Rodriguez Pardo, Pierre Delobel, Jaime Lora-Tamayo, Mikel Mancheño-Losa, Maria Luisa Sorlí Redó, José María Barbero Allende, Cédric Arvieux, Danguole Vaznaisiène, Thomas Bauer, Anne-Laure Roux, Latifa Noussair, Stéphane Corvec, Marta Fernández-Sampedro, Nicolò Rossi, Adrien Lemaignen, Mauro José Costa Salles, Taiana Cunha Ribeiro, Julien Mazet, Milène Sasso, Jean-Philippe Lavigne, Albert Sotto, Etienne Canouï, Éric Senneville, Pauline Thill, Olivier Lortholary, Fanny Lanternier, Laura Morata, Alex Soriano, Gérard Giordano, Camille Fourcade, Bernhard J H Franck, Jochen G Hofstätter, Clara Duran, Eric Bonnet","doi":"10.1093/cid/ciae395","DOIUrl":"https://doi.org/10.1093/cid/ciae395","url":null,"abstract":"<p><strong>Background: </strong>Prosthetic joint infection (PJI) caused by Candida spp is a severe complication of arthroplasty. We investigated the outcomes of Candida PJI.</p><p><strong>Methods: </strong>This was a retrospective observational multinational study including patients diagnosed with Candida-related PJI between 2010 and 2021. Treatment outcome was assessed at 2-year follow-up.</p><p><strong>Results: </strong>A total of 269 patients were analyzed. Median age was 73.0 (interquartile range [IQR], 64.0-79.0) years; 46.5% of patients were male and 10.8% were immunosuppressed. Main infection sites were hip (53.0%) and knee (43.1%), and 33.8% patients had fistulas. Surgical procedures included debridement, antibiotics, and implant retention (DAIR) (35.7%), 1-stage exchange (28.3%), and 2-stage exchange (29.0%). Candida spp identified were Candida albicans (55.8%), Candida parapsilosis (29.4%), Candida glabrata (7.8%), and Candida tropicalis (5.6%). Coinfection with bacteria was found in 51.3% of cases. The primary antifungal agents prescribed were azoles (75.8%) and echinocandins (30.9%), administered for a median of 92.0 (IQR, 54.5-181.3) days. Cure was observed in 156 of 269 (58.0%) cases. Treatment failure was associated with age >70 years (OR, 1.811 [95% confidence interval {CI}: 1.079-3.072]), and the use of DAIR (OR, 1.946 [95% CI: 1.157-3.285]). Candida parapsilosis infection was associated with better outcome (OR, 0.546 [95% CI: .305-.958]). Cure rates were significantly different between DAIR versus 1-stage exchange (46.9% vs 67.1%, P = .008) and DAIR versus 2-stage exchange (46.9% vs 69.2%, P = .003), but there was no difference comparing 1- to 2-stage exchanges (P = .777).</p><p><strong>Conclusions: </strong>Candida PJI prognosis seems poor, with high rate of failure, which does not appear to be linked to immunosuppression, use of azoles, or treatment duration.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-27","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142072203","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}
Pedro Landete, Olga-Adriana Caliman-Sturdza, Jose A Lopez-Martin, Liliana Preotescu, Mihaela-Catalina Luca, Anastasia Kotanidou, Paula Villares, Shirley-Patricia Iglesias, Pablo Guisado-Vasco, Elena-Maria Saiz-Lou, Maria Del Carmen Farinas-Alvarez, Esperanza Merino de Lucas, Eduardo Perez-Alba, Jose-Miguel Cisneros, Vicente Estrada, Carmen Hidalgo-Tenorio, Garyfallia Poulakou, Miguel Torralba, Jesus Fortun, Paula Garcia-Ocana, Adrien Lemaignen, Miguel Marcos-Martin, Maria Molina, Roger Paredes, Maria Teresa Perez-Rodriguez, Dimitar Raev, Pablo Ryan, Fernanda Meira, Javier Gomez, Nadia Torres, Diego Lopez-Mendoza, Jose Jimeno, Jose-Felipe Varona
Background: Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients.
Methods: Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety.
Findings: After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated.
Interpretation: Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted.
Funding: This trial has been funded by Pharmamar, S.A. (Madrid, Spain).
背景:普利替普酶对SARS-CoV-2具有很强的临床前活性,在一项针对COVID-19住院患者的I期试验中,普利替普酶的耐受性普遍良好。NEPTUNO 是一项 III 期多中心随机对照试验,旨在评估普利肝素治疗中度 COVID-19 住院成年患者的疗效和安全性:纳入的患者均有 SARS-CoV-2 感染记录,需要氧气治疗,且器官功能正常。计划样本量为 609 例患者。患者按1:1:1的比例随机接受至少3天的地塞米松加普利替平(1.5毫克/天或2.5毫克/天,共3天)或标准治疗(对照组)。主要终点是持续停止补充氧气的时间。次要终点包括持续出院时间、临床状态、氧气支持持续时间、需要入住重症监护室的患者比例以及安全性:在对205名患者进行随机分组后,由于与COVID-19相关的住院率显著下降,NEPTUNO被终止。现有数据显示,停用持续氧疗的中位时间(5天 vs 7天)缩短了2天,普利替平治疗组更有利(普利替平1.5毫克 vs 对照组的危险比[HR]为1.37,95%置信区间[CI]为0.96-1.96,P=0.08;普利替平2.5毫克 vs 对照组的危险比[HR]为1.06,95%置信区间[CI]为0.73-1.53,P=0.78)。普利替普酶的耐受性总体良好:尽管试验存在局限性,但这些结果表明,普利替普酶在治疗需要氧疗的患者方面可能具有积极的效益-风险比。有必要对普利替平进行进一步研究,包括对免疫抑制患者的研究:本试验由西班牙马德里 Pharmamar 公司资助。
{"title":"A phase III randomized controlled trial of plitidepsin, a marine derived compound, in hospitalized adults with moderate COVID-19.","authors":"Pedro Landete, Olga-Adriana Caliman-Sturdza, Jose A Lopez-Martin, Liliana Preotescu, Mihaela-Catalina Luca, Anastasia Kotanidou, Paula Villares, Shirley-Patricia Iglesias, Pablo Guisado-Vasco, Elena-Maria Saiz-Lou, Maria Del Carmen Farinas-Alvarez, Esperanza Merino de Lucas, Eduardo Perez-Alba, Jose-Miguel Cisneros, Vicente Estrada, Carmen Hidalgo-Tenorio, Garyfallia Poulakou, Miguel Torralba, Jesus Fortun, Paula Garcia-Ocana, Adrien Lemaignen, Miguel Marcos-Martin, Maria Molina, Roger Paredes, Maria Teresa Perez-Rodriguez, Dimitar Raev, Pablo Ryan, Fernanda Meira, Javier Gomez, Nadia Torres, Diego Lopez-Mendoza, Jose Jimeno, Jose-Felipe Varona","doi":"10.1093/cid/ciae227","DOIUrl":"https://doi.org/10.1093/cid/ciae227","url":null,"abstract":"<p><strong>Background: </strong>Plitidepsin has shown potent preclinical activity against SARS-CoV-2 and was generally well tolerated in a Phase I trial of hospitalized patients with COVID-19. NEPTUNO, a Phase III, multicenter, randomized, controlled trial, was designed to evaluate the efficacy and safety of plitidepsin in the management of moderate COVID-19 in hospitalized adult patients.</p><p><strong>Methods: </strong>Included patients had documented SARS-CoV-2 infection, required oxygen therapy, and had adequate organ function. The planned sample size was 609 patients. Patients were randomized 1:1:1 to at least 3 days of dexamethasone plus either plitidepsin (1.5 mg/day or 2.5 mg/day, for 3 days) or standard of care (control). The primary endpoint was the time to sustained withdrawal of supplemental oxygen. Secondary endpoints included time to sustained hospital discharge, clinical status, duration of oxygen support, percentage of patients requiring admission to the intensive care unit, and safety.</p><p><strong>Findings: </strong>After randomizing 205 patients, NEPTUNO was discontinued due to a notable drop in COVID-19-related hospitalizations. Available data suggest a 2-day improvement in the median time to sustained oxygen therapy discontinuation (5 vs 7 days) favoring both plitidepsin arms (hazard ratio [HR] 1.37, 95% confidence interval [CI] 0.96-1.96, p=0.08 for plitidepsin 1.5 mg vs control; HR 1.06, 95% CI 0.73-1.53, p=0.78 for plitidepsin 2.5 mg vs control). Plitidepsin was generally well tolerated.</p><p><strong>Interpretation: </strong>Despite the trial limitations, these results suggest that plitidepsin may have a positive benefit-risk ratio in the management of patients requiring oxygen therapy. Further studies with plitidepsin, including those in immunosuppressed patients, are warranted.</p><p><strong>Funding: </strong>This trial has been funded by Pharmamar, S.A. (Madrid, Spain).</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-26","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142055189","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}
Jane Gakuru, Enock Kagimu, Biyue Dai, Samuel Okurut, Laura Nsangi, Nathan C Bahr, Michael Okirwoth, Olivie C Namuju, Joseph N Jarvis, David S Lawrence, Cynthia Ahimbisibwe, Jayne Ellis, Kizza Kandole Tadeo, David R Boulware, David B Meya, Lillian Tugume
Background: In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.
Methods: We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.
Results: During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144).
Conclusion: The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.
{"title":"Implementation of single high-dose liposomal amphotericin B based induction therapy for treatment of HIV-associated cryptococcal meningitis in Uganda: a comparative prospective cohort study.","authors":"Jane Gakuru, Enock Kagimu, Biyue Dai, Samuel Okurut, Laura Nsangi, Nathan C Bahr, Michael Okirwoth, Olivie C Namuju, Joseph N Jarvis, David S Lawrence, Cynthia Ahimbisibwe, Jayne Ellis, Kizza Kandole Tadeo, David R Boulware, David B Meya, Lillian Tugume","doi":"10.1093/cid/ciae413","DOIUrl":"https://doi.org/10.1093/cid/ciae413","url":null,"abstract":"<p><strong>Background: </strong>In 2022, the World Health Organization (WHO) recommended a single 10mg/kg dose of liposomal amphotericin B in combination with 14 days of flucytosine and fluconazole (AMBITION-cm regimen) for induction therapy of HIV-associated cryptococcal meningitis, based on the results of the multisite AMBITION-cm trial. We evaluated outcomes after real-world implementation of this novel regimen in Uganda.</p><p><strong>Methods: </strong>We enrolled Ugandan adults with cryptococcal meningitis into an observational cohort receiving the AMBITION-cm regimen with therapeutic lumbar punctures in routine care during 2022-2023. We compared 10-week survival and CSF early fungicidal activity with the outcomes observed in the AMBITION-cm clinical trial conducted at the same sites.</p><p><strong>Results: </strong>During 2022-2023, 179 adults were treated with the AMBITION-cm regimen via routine care and compared to the 171 adults randomized to the AMBITION-cm trial interventional arm in Uganda from 2018-2021. No significant difference in 10-week survival occurred between the observational cohort (68.6%; 95%CI 61.6%-76.3%) and AMBITION-cm trial participants in the intervention arm (71.7%; 95%CI 65.2%-78.8%; absolute risk difference = -3.1%; 95%CI -13.1% to 6.9%; p=.61). Early fungicidal activity did not differ (0.42 vs 0.39 log10CFU/mL/day; p=.80) between groups. Among observational cohort participants discharged alive initially and for whom follow up data were available, the incidence of re-hospitalizations due to persistently elevated intracranial pressure was 2.8% (4/144).</p><p><strong>Conclusion: </strong>The AMBITION-cm regimen for cryptococcal meningitis resulted in similar outcomes as observed in the AMBITION-cm clinical trial when implemented in routine care. Intracranial pressure management during hospitalization and awareness after discharge are key components of optimizing outcomes.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046426","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":"The end of toxoid vaccine development for preventing Clostridioides difficile infections?","authors":"Ed J Kuijper, Dale N Gerding","doi":"10.1093/cid/ciae412","DOIUrl":"https://doi.org/10.1093/cid/ciae412","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142043844","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}
Paul Feuerstadt, Teena Chopra, Whitfield Knapple, Nicholas W Van Hise, Erik R Dubberke, Brian Baggott, Beth Guthmueller, Lindy Bancke, Michael Gamborg, Theodore S Steiner, Daniel Van Handel, Sahil Khanna
Objective: To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.
Design: PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively.
Results: Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups.
Conclusions: RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population.
Clinical trial registration: The study is registered at ClinicalTrials.gov (NCT03931941).
{"title":"PUNCH CD3-OLS: a phase 3 prospective observational cohort study to evaluate the safety and efficacy of fecal microbiota, live-jslm (REBYOTA) in adults with recurrent Clostridioides difficile infection.","authors":"Paul Feuerstadt, Teena Chopra, Whitfield Knapple, Nicholas W Van Hise, Erik R Dubberke, Brian Baggott, Beth Guthmueller, Lindy Bancke, Michael Gamborg, Theodore S Steiner, Daniel Van Handel, Sahil Khanna","doi":"10.1093/cid/ciae437","DOIUrl":"https://doi.org/10.1093/cid/ciae437","url":null,"abstract":"<p><strong>Objective: </strong>To evaluate the safety and efficacy of fecal microbiota, live-jslm (RBL; REBYOTA) - the first single-dose, broad consortia microbiota-based live biotherapeutic approved by the United States (US) Food and Drug Administration for preventing recurrent Clostridioides difficile infection (rCDI) in adults following standard-of-care (SOC) antibiotic treatment.</p><p><strong>Design: </strong>PUNCH CD3-OLS was a prospective, phase 3, open-label study, conducted across the US and Canada. Participants were aged ≥18 years with documented rCDI and confirmed use of SOC antibiotics. Participants with comorbidities including inflammatory bowel disease and mild-to-moderate immunocompromising conditions could be enrolled. A single dose of RBL was rectally administered within 24-72h of antibiotic completion. The primary endpoint was the number of participants with RBL- or administration-related treatment-emergent adverse events (TEAEs). Secondary endpoints included treatment success and sustained clinical response, at 8 weeks and 6 months after RBL administration, respectively.</p><p><strong>Results: </strong>Overall, 793 participants were enrolled, of whom 697 received RBL. TEAEs through 8 weeks after administration were reported by 47.3% of participants; most events were mild or moderate gastrointestinal disorders. Serious TEAEs were reported by 3.9% of participants. The treatment success rate at 8 weeks was 73.8%; in participants who achieved treatment success, the sustained clinical response rate at 6 months was 91.0%. Safety and efficacy rates were similar across demographic and baseline characteristic subgroups.</p><p><strong>Conclusions: </strong>RBL was safe and efficacious in participants with rCDI and common comorbidities. This is the largest microbiota-based live biotherapeutic study to date and findings support use of RBL to prevent rCDI in a broad patient population.</p><p><strong>Clinical trial registration: </strong>The study is registered at ClinicalTrials.gov (NCT03931941).</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046427","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}
Joseph E Marcus, Heather C Yun, Alice E Barsoumian
Introduction: Infectious diseases physicians invest significant time mentoring medical students and internal medicine residents through research projects as well as case reports. While having an infectious diseases mentor has been shown to be associated with subsequent infectious diseases fellowship application, the impact of specific scholarly activities on future application to infectious diseases fellowship is unknown.
Methods: All research and case reports published or presented from Brooke Army Medical Center between 2014-2022 with an infectious diseases senior author and a medical student or internal medicine resident first author were evaluated. The presentations and publications that resulted from each project as well as whether the trainee applied to infectious diseases were recorded.
Results: During the study period, 16 faculty mentored 35 medical student and resident research projects and 26 case reports. Research and case reports were primarily performed by residents (88% and 96% respectively). Compared to case reports, research projects were more likely to be presented at national meetings (77% vs 32%, p=0.0009). Of the 55 projects performed by trainees who completed training, research was associated with greater rates of infectious disease fellowship application as compared to case reports (41% vs. 4%, p=0.0012).
Conclusion: Internal medicine resident and medical student involvement in research mentored by an infectious disease physician was associated with a greater infectious diseases fellowship application rate as compared to those who were mentored for case reports. Investment in trainee research may be a strategy for recruiting the next generation of infectious diseases physicians.
{"title":"The Impact of Infectious Diseases Scholarly Mentorship on Subsequent Infectious Disease Fellowship Application.","authors":"Joseph E Marcus, Heather C Yun, Alice E Barsoumian","doi":"10.1093/cid/ciae438","DOIUrl":"https://doi.org/10.1093/cid/ciae438","url":null,"abstract":"<p><strong>Introduction: </strong>Infectious diseases physicians invest significant time mentoring medical students and internal medicine residents through research projects as well as case reports. While having an infectious diseases mentor has been shown to be associated with subsequent infectious diseases fellowship application, the impact of specific scholarly activities on future application to infectious diseases fellowship is unknown.</p><p><strong>Methods: </strong>All research and case reports published or presented from Brooke Army Medical Center between 2014-2022 with an infectious diseases senior author and a medical student or internal medicine resident first author were evaluated. The presentations and publications that resulted from each project as well as whether the trainee applied to infectious diseases were recorded.</p><p><strong>Results: </strong>During the study period, 16 faculty mentored 35 medical student and resident research projects and 26 case reports. Research and case reports were primarily performed by residents (88% and 96% respectively). Compared to case reports, research projects were more likely to be presented at national meetings (77% vs 32%, p=0.0009). Of the 55 projects performed by trainees who completed training, research was associated with greater rates of infectious disease fellowship application as compared to case reports (41% vs. 4%, p=0.0012).</p><p><strong>Conclusion: </strong>Internal medicine resident and medical student involvement in research mentored by an infectious disease physician was associated with a greater infectious diseases fellowship application rate as compared to those who were mentored for case reports. Investment in trainee research may be a strategy for recruiting the next generation of infectious diseases physicians.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142139519","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}
Curtis J Donskey, Erik R Dubberke, Nicola P Klein, Elizabeth G Liles, Katarzyna Szymkowiak, Mark H Wilcox, Jody Lawrence, Salim Bouguermouh, Haiying Zhang, Kenneth Koury, Ruth Bailey, Helen M Smith, Stephen Lockhart, Erik Lamberth, Warren V Kalina, Michael W Pride, Chris Webber, Annaliesa S Anderson, Kathrin U Jansen, William C Gruber, Nicholas Kitchin
Background: Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.
Methods: This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N=17,535) to receive 3 PF-06425090 or placebo doses (0,1,6-months). Primary endpoints were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary endpoints), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability/safety was assessed.
Results: The primary endpoint was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE)=31.0% (96.4%CI: -38.7%-66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE=28.6% (-28.4%-61.0%)]). Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P=0.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE=100% [95%CI: 59.6%-100.0%]) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE=100% [54.8%-100.0%]). Local reactions were more frequent in PF-06425090 recipients and systemic events were generally similar between groups; most were mild-to-moderate. AE rates were similar between groups.
Conclusions: Three PF-06425090 doses were safe and well-tolerated. Although the primary endpoint was not met, PF-06425090 reduced symptom duration, CDI requiring medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. NCT03090191.
{"title":"CLOVER: A Phase 3 Randomized Trial Investigating the Efficacy and Safety of a Detoxified Toxin A/B Vaccine in Adults 50 Years and Older at Increased Risk of Clostridioides difficile Infection.","authors":"Curtis J Donskey, Erik R Dubberke, Nicola P Klein, Elizabeth G Liles, Katarzyna Szymkowiak, Mark H Wilcox, Jody Lawrence, Salim Bouguermouh, Haiying Zhang, Kenneth Koury, Ruth Bailey, Helen M Smith, Stephen Lockhart, Erik Lamberth, Warren V Kalina, Michael W Pride, Chris Webber, Annaliesa S Anderson, Kathrin U Jansen, William C Gruber, Nicholas Kitchin","doi":"10.1093/cid/ciae410","DOIUrl":"https://doi.org/10.1093/cid/ciae410","url":null,"abstract":"<p><strong>Background: </strong>Clostridioides difficile infection (CDI) causes substantial mortality and healthcare burden. We assessed the detoxified toxin-A/B PF-06425090 vaccine for primary CDI prevention.</p><p><strong>Methods: </strong>This phase 3 observer-blinded study randomized (1:1) ≥50-year-olds at increased CDI risk (N=17,535) to receive 3 PF-06425090 or placebo doses (0,1,6-months). Primary endpoints were first CDI episode (≥3 unformed stools within 24 hours; central laboratory-confirmed toxin A/B positive) ≥14 days post-dose 3 (PD3; first primary) and post-dose 2 (PD2; second primary). CDI duration, need for CDI-related medical attention (secondary endpoints), and antibiotic use (post hoc analysis) PD3 were evaluated. Tolerability/safety was assessed.</p><p><strong>Results: </strong>The primary endpoint was not met (17 PF-06425090 and 25 placebo recipients had first CDI episode ≥14 days PD3 [vaccine efficacy (VE)=31.0% (96.4%CI: -38.7%-66.6%)]; 24 PF-06425090 and 34 placebo recipients had first CDI episode ≥14 days PD2 [VE=28.6% (-28.4%-61.0%)]). Median CDI duration was lower with PF-06425090 (1 day) versus placebo (4 days; 2-sided nominal P=0.02). Of participants with first CDI episode, 0 PF-06425090 and 11 placebo recipients sought CDI-related medical attention (post hoc analysis estimated VE=100% [95%CI: 59.6%-100.0%]) and 0 PF-06425090 and 10 placebo recipients required antibiotic treatment (VE=100% [54.8%-100.0%]). Local reactions were more frequent in PF-06425090 recipients and systemic events were generally similar between groups; most were mild-to-moderate. AE rates were similar between groups.</p><p><strong>Conclusions: </strong>Three PF-06425090 doses were safe and well-tolerated. Although the primary endpoint was not met, PF-06425090 reduced symptom duration, CDI requiring medical attention, and CDI-directed antibiotic treatment, highlighting its potential to reduce CDI-associated healthcare burden. NCT03090191.</p>","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142046425","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":"Chances/Challenges of the Role of New Beta-lactamase Inhibitors Against the Growing Threat of NDM-producing Escherichia coli With Penicillin-binding Protein 3 Mutations.","authors":"Claudia Fabrizio, Carlo Tascini","doi":"10.1093/cid/ciae343","DOIUrl":"https://doi.org/10.1093/cid/ciae343","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035377","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}
Lottie Brown, Mario Cruciani, J Peter Donnelly, Riina Rautemaa-Richardson, P Lewis White
{"title":"PCR diagnosis of Pneumocystis pneumonia.","authors":"Lottie Brown, Mario Cruciani, J Peter Donnelly, Riina Rautemaa-Richardson, P Lewis White","doi":"10.1093/cid/ciae430","DOIUrl":"https://doi.org/10.1093/cid/ciae430","url":null,"abstract":"","PeriodicalId":10463,"journal":{"name":"Clinical Infectious Diseases","volume":null,"pages":null},"PeriodicalIF":8.2,"publicationDate":"2024-08-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"142035378","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}