N. Petersiel, Joshua S Davis, Niamh Meagher, David J Price, Steven Y C Tong, D. Lye, D. Yahav, Archana Sud, J Owen Robinson, Jane Nelson, Sophia Archuleta, Matthew A Roberts, Alan Cass, David L. Paterson, H. Foo, Mical Paul, Stephen Guy, A. Tramontana, G. Walls, Stephen McBride, Narin Bak, N. Ghosh, Benjamin A. Rogers, Anna P. Ralph, Jane Davies, Patricia E. Ferguson, R. Dotel, Genevieve L McKew, Timothy J. Gray, Natasha E. Holmes, Simon Smith, M. Warner, S. Kalimuddin, B. Young, Naomi Runnegar, David N Andresen, Nicholas A. Anagnostou, Sandra Johnson, Mark D. Chatfield, Allen C. Cheng, Vance G Fowler, Benjamin P. Howden, Niamh Meagher, David J Price, S. V. van Hal, Matthew V N O Sullivan
Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints. We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy. Participants assigned combination therapy had a 54.5% (95% CI 48.9-60.1; p=0.11) probability and a 1.2-fold odds (95% CI 0.95–1.50; p=0.12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI 49.5-61.7; p=0.07) and 55.3% (95% CI 49.2-61.4; p=0.08) probability of having a worse outcome than participants in the standard treatment group, respectively. When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteraemia.
结果可取性排序（DOOR）是一种新兴的临床试验结果测量方法，它使用序数量表将疗效和安全性终点结合在一起。 我们将之前验证过的 DOOR 终点应用于患有耐甲氧西林金黄色葡萄球菌菌血症（MRSAB）的 CAMERA2 试验参与者队列。参与者被随机分配接受标准疗法或标准疗法加抗葡萄球菌β-内酰胺类药物（联合疗法）。我们为每位参与者分配了一个 DOOR 类别，并根据他们的住院时间（LOS）和静脉注射抗生素治疗的持续时间对他们进行了进一步的排序。我们计算了接受联合疗法的患者比接受标准疗法的患者预后更差的概率和广义几率比。 与接受标准疗法的患者相比，接受联合疗法的患者预后较差的概率为 54.5% (95% CI 48.9-60.1; p=0.11)，几率为 1.2 倍 (95% CI 0.95-1.50; p=0.12)。如果根据病程和抗生素治疗持续时间进一步排序，联合治疗组患者比标准治疗组患者预后更差的概率分别为 55.6% (95% CI 49.5-61.7; p=0.07) 和 55.3% (95% CI 49.2-61.4; p=0.08)。 如果同时考虑疗效和安全性，采用标准疗法和β-内酰胺类药物联合治疗MRSAB可能会比标准疗法的临床效果更差。不过，也不能排除联合疗法的微小益处。联合疗法的毒性很可能大于加快清除菌血症所带来的益处。
{"title":"Combination of anti-staphylococcal β lactam with standard therapy compared to standard therapy alone for the treatment of MRSA bacteraemia: a post hoc analysis of the CAMERA2 trial using a desirability of outcome ranking (DOOR) approach","authors":"N. Petersiel, Joshua S Davis, Niamh Meagher, David J Price, Steven Y C Tong, D. Lye, D. Yahav, Archana Sud, J Owen Robinson, Jane Nelson, Sophia Archuleta, Matthew A Roberts, Alan Cass, David L. Paterson, H. Foo, Mical Paul, Stephen Guy, A. Tramontana, G. Walls, Stephen McBride, Narin Bak, N. Ghosh, Benjamin A. Rogers, Anna P. Ralph, Jane Davies, Patricia E. Ferguson, R. Dotel, Genevieve L McKew, Timothy J. Gray, Natasha E. Holmes, Simon Smith, M. Warner, S. Kalimuddin, B. Young, Naomi Runnegar, David N Andresen, Nicholas A. Anagnostou, Sandra Johnson, Mark D. Chatfield, Allen C. Cheng, Vance G Fowler, Benjamin P. Howden, Niamh Meagher, David J Price, S. V. van Hal, Matthew V N O Sullivan","doi":"10.1093/ofid/ofae181","DOIUrl":"https://doi.org/10.1093/ofid/ofae181","url":null,"abstract":"\u0000 \u0000 \u0000 Desirability of outcome ranking (DOOR) is an emerging approach to clinical trial outcome measurement using an ordinal scale to incorporate efficacy and safety endpoints.\u0000 \u0000 \u0000 \u0000 We applied a previously validated DOOR endpoint to a cohort of CAMERA2 trial participants with methicillin-resistant Staphylococcus aureus bacteraemia (MRSAB). Participants were randomly assigned to standard therapy, or to standard therapy plus an anti-staphylococcal β-lactam (combination therapy). Each participant was assigned a DOOR category, within which they were further ranked according to their hospital length of stay (LOS) and duration of intravenous antibiotic treatment. We calculated the probability and the generalized odds ratio of participants receiving combination therapy having worse outcomes than those receiving standard therapy.\u0000 \u0000 \u0000 \u0000 Participants assigned combination therapy had a 54.5% (95% CI 48.9-60.1; p=0.11) probability and a 1.2-fold odds (95% CI 0.95–1.50; p=0.12) of having a worse outcome than participants on standard therapy. When further ranked according to LOS and duration of antibiotic treatment, participants in the combination group had a 55.6% (95% CI 49.5-61.7; p=0.07) and 55.3% (95% CI 49.2-61.4; p=0.08) probability of having a worse outcome than participants in the standard treatment group, respectively.\u0000 \u0000 \u0000 \u0000 When considering both efficacy and safety, treatment of MRSAB with a combination of standard therapy and a β-lactam likely results in a worse clinical outcome than standard therapy. However, a small benefit of combination therapy cannot be excluded. Most likely the toxicity of combination therapy outweighed any benefit from faster clearance of bacteraemia.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"66 18","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655858","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
S. Shan, Weixin Zhang, Huizhi Gao, Pei-Yu Huang, Zhanwei Du, Yuan Bai, Y. Lau, Dongxuan Chen, Eric HY Lau, Joshua Nealon, Peng Wu
Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.
{"title":"Global seasonal activities of respiratory syncytial virus before the COVID-19 pandemic: a systematic review","authors":"S. Shan, Weixin Zhang, Huizhi Gao, Pei-Yu Huang, Zhanwei Du, Yuan Bai, Y. Lau, Dongxuan Chen, Eric HY Lau, Joshua Nealon, Peng Wu","doi":"10.1093/ofid/ofae238","DOIUrl":"https://doi.org/10.1093/ofid/ofae238","url":null,"abstract":"\u0000 Varied seasonal patterns of respiratory syncytial virus (RSV) have been reported worldwide. We conducted a systematic review on articles identified in PubMed reporting RSV seasonality based on data collected before 1 January 2020. RSV seasonal patterns were examined by geographic location, calendar month, analytic method and meteorological factors including temperature and absolute humidity. Correlation and regression analyses were conducted to explore the relationship between RSV seasonality and study methods and characteristics of study locations. RSV seasons were reported in 209 articles published in 1973-2023 for 317 locations in 77 countries. Regular RSV seasons were similarly reported in countries in temperate regions, with highly variable seasons identified in subtropical and tropical countries. Longer durations of RSV seasons were associated with a higher daily average mean temperature and daily average mean absolute humidity. The global seasonal patterns of RSV provided important information for optimizing interventions against RSV infection.","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"2 11","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654867","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Frank P Tverdek, S. Aitken, V. Mulanovich, Javier A Adachi, Cai Wu, Sherry Cantu, P. McDaneld, Roy F. Chemaly
Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established. An antimicrobial time-out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: Period 1 (pre time-out: 1/2007–6/2010) and Period 2 (post time-out: 7/2010 –3/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1,000 patient days (DOT/1000 PD) were also assessed. Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 d (95% CI -1.38 – -0.41); linezolid: -0.89 d (95% CI -1.27 – -0.52); meropenem: -0.97 d (95% CI -1.39 – -0.56); tigecycline: -1.41 d (95% CI -2.19 – -0.63); p < 0.001 for each comparison. DOT/1000 PD decreased significantly for meropenem (-43.49, 95% CI -58.61 – -28.37, p < 0.001), tigecycline (-35.47, 95% CI -44.94 – -26.00, p < 0.001), and daptomycin (-9.47, 95% CI -15.25 – -3.68, p = 0.002). A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.
抗菌药物管理计划可以优化抗菌药物的使用，联邦政府已强制要求所有医院实施该计划。然而，针对免疫力低下的癌症患者的最佳管理实践尚未得到很好的确立。 一家综合癌症中心以电子邮件的形式向住院患者的主治医师发送了抗菌药物超时通知，患者使用靶向抗菌药物（达托霉素、利奈唑烷、替加环素、万古霉素、亚胺培南/西司他丁、美罗培南）治疗达到 5 天后，医生将停用这些药物。如果没有必要，医生应停用抗菌药物，或记录继续使用的理由。这是一项准实验性间断时间序列分析，评估以下时间段的抗菌药物使用情况：第一阶段（超时前：2007 年 1 月至 2010 年 6 月）和第二阶段（超时后：2010 年 7 月至 2015 年 3 月）。抗菌素消耗的主要指标是平均治疗时间。此外，还评估了每千名患者的治疗天数（DOT/1000 PD）。 暂停使用与以下抗菌药物的平均治疗时间显著缩短有关：达托霉素：-0.89 天（95% CI -1.38 --0.41）；利奈唑烷：-0.89 天（95% CI -1.27 --0.52）；美罗培南：-0.97 天（95% CI -1.39 --0.56）；替加环素：-1.41 天（95% CI -2.19 --0.63）；各项比较的 p <0.001。美罗培南（-43.49，95% CI -58.61 -28.37，p <0.001）、替加环素（-35.47，95% CI -44.94 -26.00，p <0.001）和达托霉素（-9.47，95% CI -15.25 -3.68，p = 0.002）的 DOT/1000 PD 显著下降。 第 5 天被动超时与癌症中心减少靶向抗生素的使用有关，有可能被成功应用于多种环境和电子健康记录中。
{"title":"Implementation of an Automated Antibiotic Time Out at a Comprehensive Cancer Center","authors":"Frank P Tverdek, S. Aitken, V. Mulanovich, Javier A Adachi, Cai Wu, Sherry Cantu, P. McDaneld, Roy F. Chemaly","doi":"10.1093/ofid/ofae235","DOIUrl":"https://doi.org/10.1093/ofid/ofae235","url":null,"abstract":"\u0000 \u0000 \u0000 Antimicrobial stewardship programs can optimize antimicrobial use and have been federally mandated in all hospitals. However, best stewardship practices in immunocompromised patients with cancer are not well established.\u0000 \u0000 \u0000 \u0000 An antimicrobial time-out, in the form of an email, was sent to physicians caring for hospitalized patients reaching 5 days of therapy for targeted antimicrobials (daptomycin, linezolid, tigecycline, vancomycin, imipenem/cilastatin, meropenem) in a comprehensive cancer center. Physicians were to discontinue the antimicrobial if unnecessary or document a rationale for continuation. This is a quasi-experimental, interrupted time series analysis assessing antimicrobial use during the following times: Period 1 (pre time-out: 1/2007–6/2010) and Period 2 (post time-out: 7/2010 –3/2015). The primary antimicrobial consumption metric was mean duration of therapy. Days of therapy per 1,000 patient days (DOT/1000 PD) were also assessed.\u0000 \u0000 \u0000 \u0000 Implementation of the time-out was associated with a significant decrease in mean duration of therapy for the following antimicrobials; daptomycin: -0.89 d (95% CI -1.38 – -0.41); linezolid: -0.89 d (95% CI -1.27 – -0.52); meropenem: -0.97 d (95% CI -1.39 – -0.56); tigecycline: -1.41 d (95% CI -2.19 – -0.63); p < 0.001 for each comparison. DOT/1000 PD decreased significantly for meropenem (-43.49, 95% CI -58.61 – -28.37, p < 0.001), tigecycline (-35.47, 95% CI -44.94 – -26.00, p < 0.001), and daptomycin (-9.47, 95% CI -15.25 – -3.68, p = 0.002).\u0000 \u0000 \u0000 \u0000 A passive day 5 time-out was associated with reduction in targeted antibiotic use in a cancer center and could potentially be successfully adopted to several settings and electronic health records.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"82 16","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140655163","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sahar Saeed, Tyler Thomas, Duy Dinh, Erica Moodie, Joseph Cox, Curtis Cooper, John Gill, V. Martel-Laferrière, Dimitra Panagiotoglou, Sharon Walmsley, Alexander Wong, M. Klein
The cascade of care, commonly used to assess HIV and Hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals’ engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people living with HIV and HCV. We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers bi-annually. Markov multi-state models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) Lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) Re-engaged (re-entry into cohort after being LTFU); (3) Withdrawn from the study (i.e. moved); (4) Death; otherwise remained (5) engaged-in-care. 1809 participants met the eligibility criteria and contributed 12,591 person-years from 2003-2022. LTFU was common, with 46% experiencing at least one episode, of whom only 57% re-engaged. One in five (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (aHR 1.37, 95% CI 1.13, 1.67), evidence of HCV treatment but no sustained virologic response (SVR) result (aHR 1.99, 95% CI 1.56, 2.53) and recent incarceration (aHR 1.94 95% CI 1.58, 2.40). Being Indigenous was a significant predictor of death across all engagement trajectories. Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.
{"title":"Frequent disengagement and subsequent mortality among people living with HIV and Hepatitis C in Canada: A prospective cohort study","authors":"Sahar Saeed, Tyler Thomas, Duy Dinh, Erica Moodie, Joseph Cox, Curtis Cooper, John Gill, V. Martel-Laferrière, Dimitra Panagiotoglou, Sharon Walmsley, Alexander Wong, M. Klein","doi":"10.1093/ofid/ofae239","DOIUrl":"https://doi.org/10.1093/ofid/ofae239","url":null,"abstract":"\u0000 \u0000 \u0000 The cascade of care, commonly used to assess HIV and Hepatitis C (HCV) health service delivery, has limitations in capturing the complexity of individuals’ engagement patterns. This study examines the dynamic nature of engagement and mortality trajectories among people living with HIV and HCV.\u0000 \u0000 \u0000 \u0000 We used data from the Canadian HIV-HCV Co-Infection Cohort, which prospectively follows 2098 participants from 18 centers bi-annually. Markov multi-state models were used to evaluate sociodemographic and clinical factors associated with transitioning between the following states: (1) Lost-to-follow-up (LTFU), defined as no visit for 18 months; (2) Re-engaged (re-entry into cohort after being LTFU); (3) Withdrawn from the study (i.e. moved); (4) Death; otherwise remained (5) engaged-in-care.\u0000 \u0000 \u0000 \u0000 1809 participants met the eligibility criteria and contributed 12,591 person-years from 2003-2022. LTFU was common, with 46% experiencing at least one episode, of whom only 57% re-engaged. One in five (n = 383) participants died during the study. Participants who transitioned to LTFU were twice as likely to die as those who were consistently engaged. Factors associated with transitioning to LTFU included detectable HCV RNA (aHR 1.37, 95% CI 1.13, 1.67), evidence of HCV treatment but no sustained virologic response (SVR) result (aHR 1.99, 95% CI 1.56, 2.53) and recent incarceration (aHR 1.94 95% CI 1.58, 2.40). Being Indigenous was a significant predictor of death across all engagement trajectories.\u0000 \u0000 \u0000 \u0000 Disengagement from clinical care was common and resulted in higher death rates. People LTFU were more likely to require HCV treatment highlighting a priority population for elimination strategies.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"31 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140658910","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
G. Wafeu, Tristan M Lepage, Jérémy T. Campillo, Arnauld Efon-Ekangouo, H. Nana-Djeunga, Narcisse Nzune-Toche, A. Domche, Laurentine Sumo, G. Njitchouang, Martine Augusta Flore Tsasse, J. Bopda, Yves Aubin Balog, Yannick Niamsi-Emalio, Stève Mbickmen-Tchana, Gervais Kamga Talla, Yannick Sédrick Nguedia Kana, Félicité Diane Maga Messina, S. Pion, A. Kuesel, J. Kamgno, M. Boussinesq, C. Chesnais
In 2018, the US FDA approved the macrocylic lactone moxidectin (MOX) at 8 mg dosage for onchocerciasis treatment in individuals aged ≥12 year-old. Severe adverse reactions have occurred after ivermectin (IVM), also a macrocyclic lactone, in individuals with high Loa loa microfilaria density (MFD). This study compared the safety and efficacy of a 2 mg MOX dose and the standard 150 µg/kg IVM dose in individuals with low L loa MFD. A double-blind randomized, ivermectin-controlled, trial of a 2 mg moxidectin dose was conducted in Cameroon between May and July 2022. It enrolled 72 adult men with L. loa MFD between 5-1000 microfilaria/mL. Outcomes were occurrence of adverse events (AE) and L loa MFD reduction rate during the first month off treatment. No serious or severe AEs occurred among the 36 MOX or the 36 IVM treated individuals. Forty-nine AEs occurred in the MOX arm vs 59 AEs in the IVM arm. Grade 2 AE incidence was higher among IVM than MOX treated participants (38.5% and 14.3%, respectively, p = 0.043). Median MFD reduction rates were significantly higher after IVM than MOX at day 3 (D3) (70.2% vs 48.5%), D7 (76.4% vs 50.0%) and D30 (79.8% vs 48.1%). A single 2 mg MOX dose is as safe as 150 µg/kg IVM in patients with low L loa MFD. Further studies with higher moxidectin doses and in patients with higher MFD are warranted.
2018 年，美国 FDA 批准大环内酯莫西菌素（MOX）用于治疗年龄≥12 岁的盘尾丝虫病患者，剂量为 8 毫克。伊维菌素（IVM）也是一种大环内酯类药物，在Loa loa微丝蚴密度（MFD）较高的个体中使用后曾出现过严重的不良反应。这项研究比较了 2 毫克 MOX 剂量和 150 微克/千克 IVM 标准剂量对低罗阿微丝虫密度患者的安全性和有效性。 2022 年 5 月至 7 月期间，在喀麦隆进行了一项 2 毫克莫西菌素剂量的双盲随机伊维菌素对照试验。该试验共招募了 72 名患有 L. loa MFD（微丝蚴数量在 5-1000 个/毫升之间）的成年男性。研究结果为不良事件（AE）的发生率和停药后第一个月 L loa MFD 的减少率。 接受 MOX 治疗的 36 人和接受 IVM 治疗的 36 人均未发生严重或严重 AE。MOX治疗组发生49例AE，IVM治疗组发生59例AE。IVM 治疗参与者的 2 级 AE 发生率高于 MOX 治疗参与者（分别为 38.5% 和 14.3%，p = 0.043）。在第 3 天（D3）（70.2% 对 48.5%）、第 7 天（76.4% 对 50.0%）和第 30 天（79.8% 对 48.1%），IVM 的中位 MFD 减少率明显高于 MOX。 在低 L loa MFD 患者中，单次 2 毫克 MOX 剂量与 150 微克/千克 IVM 一样安全。有必要对更高剂量的莫希菌素和更高MFD的患者进行进一步研究。
{"title":"Safety and short-term efficacy of a single dose of 2 mg moxidectin in Loa loa infected individuals: a double-blind, randomized ivermectin-controlled trial with ascending microfilarial densities","authors":"G. Wafeu, Tristan M Lepage, Jérémy T. Campillo, Arnauld Efon-Ekangouo, H. Nana-Djeunga, Narcisse Nzune-Toche, A. Domche, Laurentine Sumo, G. Njitchouang, Martine Augusta Flore Tsasse, J. Bopda, Yves Aubin Balog, Yannick Niamsi-Emalio, Stève Mbickmen-Tchana, Gervais Kamga Talla, Yannick Sédrick Nguedia Kana, Félicité Diane Maga Messina, S. Pion, A. Kuesel, J. Kamgno, M. Boussinesq, C. Chesnais","doi":"10.1093/ofid/ofae240","DOIUrl":"https://doi.org/10.1093/ofid/ofae240","url":null,"abstract":"\u0000 \u0000 \u0000 In 2018, the US FDA approved the macrocylic lactone moxidectin (MOX) at 8 mg dosage for onchocerciasis treatment in individuals aged ≥12 year-old. Severe adverse reactions have occurred after ivermectin (IVM), also a macrocyclic lactone, in individuals with high Loa loa microfilaria density (MFD). This study compared the safety and efficacy of a 2 mg MOX dose and the standard 150 µg/kg IVM dose in individuals with low L loa MFD.\u0000 \u0000 \u0000 \u0000 A double-blind randomized, ivermectin-controlled, trial of a 2 mg moxidectin dose was conducted in Cameroon between May and July 2022. It enrolled 72 adult men with L. loa MFD between 5-1000 microfilaria/mL. Outcomes were occurrence of adverse events (AE) and L loa MFD reduction rate during the first month off treatment.\u0000 \u0000 \u0000 \u0000 No serious or severe AEs occurred among the 36 MOX or the 36 IVM treated individuals. Forty-nine AEs occurred in the MOX arm vs 59 AEs in the IVM arm. Grade 2 AE incidence was higher among IVM than MOX treated participants (38.5% and 14.3%, respectively, p = 0.043). Median MFD reduction rates were significantly higher after IVM than MOX at day 3 (D3) (70.2% vs 48.5%), D7 (76.4% vs 50.0%) and D30 (79.8% vs 48.1%).\u0000 \u0000 \u0000 \u0000 A single 2 mg MOX dose is as safe as 150 µg/kg IVM in patients with low L loa MFD. Further studies with higher moxidectin doses and in patients with higher MFD are warranted.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"6 9","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140654022","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Fazia Tadount, Marilou Kiely, Ali Assi, Ellen Rafferty, Manish Sadarangani, Shannon E MacDonald, Caroline Quach
Sex impacts individuals’ response to vaccination. However, most vaccine studies do not report these differences disaggregated by sex. The aim of this study was to assess sex differences in the immunogenicity and efficacy of influenza vaccine. We performed a meta-analysis using phase III randomized-controlled trials data conducted between 2010-2018. Using heamagglutination inhibition antibody titers for each strain, differences in geometric mean ratios (GMR) were calculated by sex. Risk ratios (RR) comparing seroconversion proportions were pooled for females and males using random-effects models. Vaccine efficacy (VE) was assessed. Data were analyzed by age group (18-64 vs. ≥65 years). A total of 33,092 healthy adults from 19 studies were included for immunogenicity analysis, and 6,740 from one study for VE. Whereas no sex differences in immunogenicity were found in adults < 65 years old, older females had a significantly greater chance to seroconvert compared to older males for all strains: RRH1N1 1·17 [1·12, 1·23]; RRH3N2 1·09 [1·05, 1·14]; RRVictoria 1·23 [1·14, 1·31]; RRYamagata 1·22 [1·14, 1·30]. GMRs were also higher in older females for all strains compared to older males. VE in preventing lab-confirmed influenza was higher in older females compared to older males with VEs of 27·32% (1·15, 46·56) and 6·06% (-37·68, 35·90), respectively. Our results suggest a higher immunogenicity and VE in females compared to males in older adults. These differences in immunogenicity and VE support the disaggregation of vaccine data by sex in clinical trials and observational studies.
{"title":"Sex Differences in the Immunogenicity and Efficacy of Seasonal Influenza Vaccines: A Meta-analysis of Randomized-Controlled Trials","authors":"Fazia Tadount, Marilou Kiely, Ali Assi, Ellen Rafferty, Manish Sadarangani, Shannon E MacDonald, Caroline Quach","doi":"10.1093/ofid/ofae222","DOIUrl":"https://doi.org/10.1093/ofid/ofae222","url":null,"abstract":"\u0000 \u0000 \u0000 Sex impacts individuals’ response to vaccination. However, most vaccine studies do not report these differences disaggregated by sex. The aim of this study was to assess sex differences in the immunogenicity and efficacy of influenza vaccine.\u0000 \u0000 \u0000 \u0000 We performed a meta-analysis using phase III randomized-controlled trials data conducted between 2010-2018. Using heamagglutination inhibition antibody titers for each strain, differences in geometric mean ratios (GMR) were calculated by sex. Risk ratios (RR) comparing seroconversion proportions were pooled for females and males using random-effects models. Vaccine efficacy (VE) was assessed. Data were analyzed by age group (18-64 vs. ≥65 years).\u0000 \u0000 \u0000 \u0000 A total of 33,092 healthy adults from 19 studies were included for immunogenicity analysis, and 6,740 from one study for VE. Whereas no sex differences in immunogenicity were found in adults < 65 years old, older females had a significantly greater chance to seroconvert compared to older males for all strains: RRH1N1 1·17 [1·12, 1·23]; RRH3N2 1·09 [1·05, 1·14]; RRVictoria 1·23 [1·14, 1·31]; RRYamagata 1·22 [1·14, 1·30]. GMRs were also higher in older females for all strains compared to older males. VE in preventing lab-confirmed influenza was higher in older females compared to older males with VEs of 27·32% (1·15, 46·56) and 6·06% (-37·68, 35·90), respectively.\u0000 \u0000 \u0000 \u0000 Our results suggest a higher immunogenicity and VE in females compared to males in older adults. These differences in immunogenicity and VE support the disaggregation of vaccine data by sex in clinical trials and observational studies.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"46 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664929","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Sabirah N. Kasule, Emily C. Fernholz, Leah Grant, Amy Kole, T. Grys, Erin Kaleta, E. Theel, B. Pritt, Erin H Graf
In 2021, the state of Arizona experienced the largest focal outbreak of West Nile Virus (WNV) in US history. Timely and accurate diagnostic testing remains a challenge for WNV due to transient viremia and limited immunoassay specificity. Recent studies have identified whole blood (WB) and urine as more sensitive specimen types for the detection of WNV RNA. We evaluated ordering practices, test performance and patient characteristics of probable and confirmed cases. In total we identified 190 probable and proven cases, including 127 patients (66.8%) with neuroinvasive disease. Among all cases, only 29.5% had WNV polymerase chain reaction (PCR) testing ordered on WB, of which 80.3% resulted as positive, including 7 cases in which WNV serologic testing was negative and 5 cases for which serologic testing was not ordered. In comparison, only 23.7% of cases that had cerebrospinal fluid (CSF) PCR ordered had a positive result, which included 3 cases that were negative by PCR on WB. In contrast, WNV PCR on WB detected 12 neuroinvasive cases that were CSF PCR negative. WNV PCR testing in urine was only ordered on 2 patients, both of which were positive. Crossing cycle threshold (Ct) values were not significantly different between WB and CSF specimen types, nor was there a correlation between Ct value and days from symptom onset at the time of sample collection; all specimen types and timepoints had Ct values, with 98% above 30. WB was positive by WNV PCR in several patients for more than 7 days (range: 7 to 25 days) after symptom onset, as was the CSF PCR. Taken together these findings indicate that WNV PCR testing on WB may be the best initial test for timely diagnosis of WNV infection, irrespective of clinical manifestation, however if negative in patients with suspected neuroinvasive disease, WNV PCR testing on CSF should be ordered.
{"title":"Whole Blood PCR Preferred for Timely Diagnosis of Neuroinvasive West Nile Virus Infections: Lessons from the 2021 Arizona Outbreak","authors":"Sabirah N. Kasule, Emily C. Fernholz, Leah Grant, Amy Kole, T. Grys, Erin Kaleta, E. Theel, B. Pritt, Erin H Graf","doi":"10.1093/ofid/ofae188","DOIUrl":"https://doi.org/10.1093/ofid/ofae188","url":null,"abstract":"\u0000 \u0000 \u0000 In 2021, the state of Arizona experienced the largest focal outbreak of West Nile Virus (WNV) in US history. Timely and accurate diagnostic testing remains a challenge for WNV due to transient viremia and limited immunoassay specificity. Recent studies have identified whole blood (WB) and urine as more sensitive specimen types for the detection of WNV RNA.\u0000 \u0000 \u0000 \u0000 We evaluated ordering practices, test performance and patient characteristics of probable and confirmed cases. In total we identified 190 probable and proven cases, including 127 patients (66.8%) with neuroinvasive disease.\u0000 \u0000 \u0000 \u0000 Among all cases, only 29.5% had WNV polymerase chain reaction (PCR) testing ordered on WB, of which 80.3% resulted as positive, including 7 cases in which WNV serologic testing was negative and 5 cases for which serologic testing was not ordered. In comparison, only 23.7% of cases that had cerebrospinal fluid (CSF) PCR ordered had a positive result, which included 3 cases that were negative by PCR on WB. In contrast, WNV PCR on WB detected 12 neuroinvasive cases that were CSF PCR negative. WNV PCR testing in urine was only ordered on 2 patients, both of which were positive. Crossing cycle threshold (Ct) values were not significantly different between WB and CSF specimen types, nor was there a correlation between Ct value and days from symptom onset at the time of sample collection; all specimen types and timepoints had Ct values, with 98% above 30. WB was positive by WNV PCR in several patients for more than 7 days (range: 7 to 25 days) after symptom onset, as was the CSF PCR.\u0000 \u0000 \u0000 \u0000 Taken together these findings indicate that WNV PCR testing on WB may be the best initial test for timely diagnosis of WNV infection, irrespective of clinical manifestation, however if negative in patients with suspected neuroinvasive disease, WNV PCR testing on CSF should be ordered.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"27 17","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140663605","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kelly W. Gagnon, William S Bradford, John Bassler, A. Nassel, E. Kay, Madison Jeziorski, Myles D Prados, Brandi McCleskey, James Kobie, Ellen Eaton
Injection-related infections continue to rise, particularly in the South. People who inject drugs are increasingly utilizing hospital services for serious injection-related infections but may be discharged to areas without harm reduction services. We explored the availability and travel time to services for HIV and substance use in Alabama.
{"title":"Community-based Services for Hospitalized Patients with Serious Injection-Related Infections in Alabama: A Brief Report","authors":"Kelly W. Gagnon, William S Bradford, John Bassler, A. Nassel, E. Kay, Madison Jeziorski, Myles D Prados, Brandi McCleskey, James Kobie, Ellen Eaton","doi":"10.1093/ofid/ofae231","DOIUrl":"https://doi.org/10.1093/ofid/ofae231","url":null,"abstract":"\u0000 Injection-related infections continue to rise, particularly in the South. People who inject drugs are increasingly utilizing hospital services for serious injection-related infections but may be discharged to areas without harm reduction services. We explored the availability and travel time to services for HIV and substance use in Alabama.","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"36 2","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-24","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140664938","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Kamilia Abdelraouf, C. Gill, Matthew Gethers, G. Tiseo, Simona Barnini, Marco Falcone, Francesco Menichetti, David P. Nicolau
In vitro-in vivo discordance in β-lactams activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance was attributed to the supra-physiologic zinc concentration in the in vitro testing media. A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam +aztreonam) were documented. The patients’ isolates were used to induce septicemia in mice and survival upon meropenem treatment was recorded. Meropenem MICs were determined in standard media and in presence of physiological zinc concentrations. Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration 4 days) were compared to 29 receiving MBL-active β-lactams. The 14-day-mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality(P < 0.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower versus MICs in zinc-unadjusted broth (≥64 mg/L). Our data provide foundational support to establish PK/PD relationships using MICs derived in physiologic zinc concentration which may better predict β-lactam therapy outcome.
{"title":"Deciphering the Efficacy of the β-Lactams in the Face of Metallo-β-lactamase Derived Resistance in Enterobacterales: Supraphysiologic Zinc in the Broth is the Culprit","authors":"Kamilia Abdelraouf, C. Gill, Matthew Gethers, G. Tiseo, Simona Barnini, Marco Falcone, Francesco Menichetti, David P. Nicolau","doi":"10.1093/ofid/ofae228","DOIUrl":"https://doi.org/10.1093/ofid/ofae228","url":null,"abstract":"\u0000 \u0000 \u0000 In vitro-in vivo discordance in β-lactams activities against metallo-ß-lactamase (MBL)-producing Enterobacterales has been described. We aimed to assess whether this discordance was attributed to the supra-physiologic zinc concentration in the in vitro testing media.\u0000 \u0000 \u0000 \u0000 A clinical and microbiological observational study of patients with bloodstream infections due to New Delhi metallo-ß-lactamase-producing Klebsiella pneumoniae was performed. Outcomes of patients treated empirically with non-MBL-active β-lactam therapy (carbapenems and ceftazidime/avibactam) and MBL-active β-lactam therapy (ceftazidime/avibactam +aztreonam) were documented. The patients’ isolates were used to induce septicemia in mice and survival upon meropenem treatment was recorded. Meropenem MICs were determined in standard media and in presence of physiological zinc concentrations.\u0000 \u0000 \u0000 \u0000 Twenty-nine patients receiving empiric non-MBL-active β-lactams (median duration 4 days) were compared to 29 receiving MBL-active β-lactams. The 14-day-mortality rates were 21% and 14%, respectively. In the murine septicemia model, meropenem treatment resulted in protection from mortality(P < 0.0001). Meropenem MICs in the physiologic zinc concentration broth were 1- to >16-fold lower versus MICs in zinc-unadjusted broth (≥64 mg/L).\u0000 \u0000 \u0000 \u0000 Our data provide foundational support to establish PK/PD relationships using MICs derived in physiologic zinc concentration which may better predict β-lactam therapy outcome.\u0000","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"15 7","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-23","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140666359","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
Jonathan H Ryder, Jenna Preusker, Jeremy Tigh, Muhammad Salman Ashraf, Danny Schroeder, T. V. Van Schooneveld
{"title":"A Critical Need: More Data on Antimicrobial Stewardship Programs in Critical Access Hospitals","authors":"Jonathan H Ryder, Jenna Preusker, Jeremy Tigh, Muhammad Salman Ashraf, Danny Schroeder, T. V. Van Schooneveld","doi":"10.1093/ofid/ofae196","DOIUrl":"https://doi.org/10.1093/ofid/ofae196","url":null,"abstract":"","PeriodicalId":510506,"journal":{"name":"Open Forum Infectious Diseases","volume":"142 ","pages":""},"PeriodicalIF":0.0,"publicationDate":"2024-04-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"140760588","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}
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