{"title":"培养证实的新生儿败血症的7天和14天抗生素疗程：一项中低收入国家的多中心随机非劣效性试验","authors":"Sourabh Dutta, Sushma Nangia, Mamta Jajoo, MangalaBharathi Sundaram, Mala Kumar, Niranjan Shivanna, Geeta Gathwala, Saudamini Nesargi, Suksham Jain, Praveen Kumar, Arvind Saili, Arun Karthik, Shalini Tripathi, Prathik Bandiya, Poonam Dalal, Pallab Ray, Valinderjeet Singh Randhawa, Karnika Saigal, Devasena Radhakrishnan, Vimla Venkatesh, Bhavana Jagannatha, Madhu Sharma, Savitha Nagaraj, Meenakshi Malik, Sarita Dogra, Suruchi Mittal, Anumeet Saini, Nisha Makkar, Maitreyi Dhir, Asmita Chandramohan, R A Pragati, Tanaya Srivastava, Lakshmi Mukundan, Naveen Benakappa, Amlin Shukla, Reeta Rasaily","doi":"10.1136/archdischild-2024-328232","DOIUrl":null,"url":null,"abstract":"<p><strong>Objective: </strong>Definitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis.</p><p><strong>Design: </strong>Randomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.</p><p><strong>Patients: </strong>Neonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted.</p><p><strong>Exclusions: </strong><i>Staphylococcus aureus</i> or fungal sepsis, and infections requiring prolonged antibiotics. We planned to enrol 350 per group, assuming 10% rate of primary outcome, +7% non-inferiority margin, one-sided 5% alpha, 90% power, 10% loss to follow-up.</p><p><strong>Intervention: </strong>7 days (no further treatment); comparison: 14 days (7 days postrandomisation).</p><p><strong>Outcomes: </strong>Primary: relapse (definite or probable) within day 21 postantibiotic completion.</p><p><strong>Secondary outcomes: </strong>composite of mortality or definite/probable/secondary sepsis and duration of hospitalisation. One interim analysis (per protocol (PP)) was planned.</p><p><strong>Results: </strong>126 and 135 subjects were recruited in 7-day and 14-day groups, respectively, with mean (SD) birth weight (BW) 2250.9 (741.1) and 2187.8 (718.8) g. The trial was terminated early, based on interim PP analysis. 2/125 and 6/130 subjects had the primary outcome in 7-day and 14-day groups, respectively (risk difference (RD)=-3.0% (99.5% CI -9.2%, +3.1%), below non-inferiority margin). The composite secondary outcome also favoured the 7-day regimen (RD: -3.7% (99.5% CI -12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: -4 days (95% CI -5 to -3)).</p><p><strong>Conclusions: </strong>A 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.</p><p><strong>Trial registration number: </strong>NCT03280147.</p>","PeriodicalId":8177,"journal":{"name":"Archives of Disease in Childhood - Fetal and Neonatal Edition","volume":" ","pages":""},"PeriodicalIF":3.9000,"publicationDate":"2025-04-25","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":"0","resultStr":"{\"title\":\"Seven-day versus 14-day antibiotic course for culture-proven neonatal sepsis: a multicentre randomised non-inferiority trial in a low and middle-income country.\",\"authors\":\"Sourabh Dutta, Sushma Nangia, Mamta Jajoo, MangalaBharathi Sundaram, Mala Kumar, Niranjan Shivanna, Geeta Gathwala, Saudamini Nesargi, Suksham Jain, Praveen Kumar, Arvind Saili, Arun Karthik, Shalini Tripathi, Prathik Bandiya, Poonam Dalal, Pallab Ray, Valinderjeet Singh Randhawa, Karnika Saigal, Devasena Radhakrishnan, Vimla Venkatesh, Bhavana Jagannatha, Madhu Sharma, Savitha Nagaraj, Meenakshi Malik, Sarita Dogra, Suruchi Mittal, Anumeet Saini, Nisha Makkar, Maitreyi Dhir, Asmita Chandramohan, R A Pragati, Tanaya Srivastava, Lakshmi Mukundan, Naveen Benakappa, Amlin Shukla, Reeta Rasaily\",\"doi\":\"10.1136/archdischild-2024-328232\",\"DOIUrl\":null,\"url\":null,\"abstract\":\"<p><strong>Objective: </strong>Definitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis.</p><p><strong>Design: </strong>Randomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.</p><p><strong>Patients: </strong>Neonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted.</p><p><strong>Exclusions: </strong><i>Staphylococcus aureus</i> or fungal sepsis, and infections requiring prolonged antibiotics. 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The composite secondary outcome also favoured the 7-day regimen (RD: -3.7% (99.5% CI -12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: -4 days (95% CI -5 to -3)).</p><p><strong>Conclusions: </strong>A 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.</p><p><strong>Trial registration number: </strong>NCT03280147.</p>\",\"PeriodicalId\":8177,\"journal\":{\"name\":\"Archives of Disease in Childhood - Fetal and Neonatal Edition\",\"volume\":\" \",\"pages\":\"\"},\"PeriodicalIF\":3.9000,\"publicationDate\":\"2025-04-25\",\"publicationTypes\":\"Journal Article\",\"fieldsOfStudy\":null,\"isOpenAccess\":false,\"openAccessPdf\":\"\",\"citationCount\":\"0\",\"resultStr\":null,\"platform\":\"Semanticscholar\",\"paperid\":null,\"PeriodicalName\":\"Archives of Disease in Childhood - Fetal and Neonatal Edition\",\"FirstCategoryId\":\"3\",\"ListUrlMain\":\"https://doi.org/10.1136/archdischild-2024-328232\",\"RegionNum\":2,\"RegionCategory\":\"医学\",\"ArticlePicture\":[],\"TitleCN\":null,\"AbstractTextCN\":null,\"PMCID\":null,\"EPubDate\":\"\",\"PubModel\":\"\",\"JCR\":\"Q1\",\"JCRName\":\"PEDIATRICS\",\"Score\":null,\"Total\":0}","platform":"Semanticscholar","paperid":null,"PeriodicalName":"Archives of Disease in Childhood - Fetal and Neonatal Edition","FirstCategoryId":"3","ListUrlMain":"https://doi.org/10.1136/archdischild-2024-328232","RegionNum":2,"RegionCategory":"医学","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":null,"EPubDate":"","PubModel":"","JCR":"Q1","JCRName":"PEDIATRICS","Score":null,"Total":0}
引用次数: 0
摘要
目的：缺乏关于新生儿败血症抗生素持续时间的明确指导。我们假设在治疗培养证实的败血症方面，7天的抗生素疗程不逊色于14天的疗程。设计：随机、对照、非劣效性试验，在一个低收入和中等收入国家的8个中心进行掩盖结果评估。患者：出生体重(BW)≥1000 g且血培养证实败血症的新生儿在敏感抗生素治疗的第7天随机分组，前提是败血症临床缓解。排除：金黄色葡萄球菌或真菌败血症，以及需要长期使用抗生素的感染。我们计划每组入组350人，假设主要转归率为10%，非劣效性裕度为+7%，alpha值为5%，功效为90%，随访损失为10%。干预：7天（无进一步治疗）；比较：14天（随机化后7天）。结果：原发性：在抗生素完成后21天内复发（明确或可能）。次要结局：死亡率或明确/可能/继发性败血症和住院时间的综合结果。计划一次中期分析（每个方案（PP））。结果：7天组126例，14天组135例，平均（SD）出生体重（BW） 2250.9 (741.1), 2187.8 (718.8) g。根据中期PP分析，试验提前终止。2/125和6/130受试者分别在7天和14天组中有主要结局(风险差异（RD)=-3.0% (99.5% CI -9.2%, +3.1%)，低于非劣效边际）。综合次要结局也有利于7天方案（RD: -3.7% (99.5% CI -12.4%至+5.1%)）。7天组住院时间较短（中位差：-4天（95% CI -5至-3））。结论：对于无并发症的新生儿细菌性脓毒症，7天疗程的抗生素治疗可能不逊色于14天疗程。试验注册号：NCT03280147。
Seven-day versus 14-day antibiotic course for culture-proven neonatal sepsis: a multicentre randomised non-inferiority trial in a low and middle-income country.
Objective: Definitive guidance regarding the duration of antibiotics for neonatal sepsis is lacking. We hypothesised that a 7-day antibiotic course is non-inferior to a 14-day course for treating culture-proven sepsis.
Design: Randomised, controlled, non-inferiority trial with masked outcome assessment in eight centres in a low and middle-income country.
Patients: Neonates with a birth weight (BW) ≥1000 g and blood culture-proven sepsis were randomised on day 7 of sensitive antibiotic therapy provided sepsis had clinically remitted.
Exclusions: Staphylococcus aureus or fungal sepsis, and infections requiring prolonged antibiotics. We planned to enrol 350 per group, assuming 10% rate of primary outcome, +7% non-inferiority margin, one-sided 5% alpha, 90% power, 10% loss to follow-up.
Intervention: 7 days (no further treatment); comparison: 14 days (7 days postrandomisation).
Outcomes: Primary: relapse (definite or probable) within day 21 postantibiotic completion.
Secondary outcomes: composite of mortality or definite/probable/secondary sepsis and duration of hospitalisation. One interim analysis (per protocol (PP)) was planned.
Results: 126 and 135 subjects were recruited in 7-day and 14-day groups, respectively, with mean (SD) birth weight (BW) 2250.9 (741.1) and 2187.8 (718.8) g. The trial was terminated early, based on interim PP analysis. 2/125 and 6/130 subjects had the primary outcome in 7-day and 14-day groups, respectively (risk difference (RD)=-3.0% (99.5% CI -9.2%, +3.1%), below non-inferiority margin). The composite secondary outcome also favoured the 7-day regimen (RD: -3.7% (99.5% CI -12.4% to +5.1%)). Duration of hospitalisation was shorter in 7-day group (median difference: -4 days (95% CI -5 to -3)).
Conclusions: A 7-day course of antibiotics may be non-inferior to a 14-day course for uncomplicated bacterial neonatal sepsis.
期刊介绍：
Archives of Disease in Childhood is an international peer review journal that aims to keep paediatricians and others up to date with advances in the diagnosis and treatment of childhood diseases as well as advocacy issues such as child protection. It focuses on all aspects of child health and disease from the perinatal period (in the Fetal and Neonatal edition) through to adolescence. ADC includes original research reports, commentaries, reviews of clinical and policy issues, and evidence reports. Areas covered include: community child health, public health, epidemiology, acute paediatrics, advocacy, and ethics.
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