Gautam Aditya, Indu Malayil B, Bhardwaj Akinchan, Sabitha Paramasivam, Deepanjali Surendran, Suryanarayana Bettadpura Shamanna, Bammigatti Chanaveerappa, Kadhiravan Tamilarasu
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India.
Department of Medicine, Jawaharlal Institute of Postgraduate Medical Education and Research, Puducherry, India
BMJ Open. 2025 Jun 23;15(6):e094409. doi: 10.1136/bmjopen-2024-094409.
Amoxicillin-clavulanate is commonly used to prevent infections following snakebites despite the lack of clinical evidence. We aimed to demonstrate that clinically directed initiation of amoxicillin-clavulanate would be non-inferior to routine use in this setting.
Open-label, randomised, non-inferiority trial with blinded adjudication of endpoints.
Emergency department of a teaching hospital in southern India.
Adults with local swelling following snakebites within 24 hours of bite.
In the routine use strategy, intravenous followed by oral amoxicillin-clavulanate was administered for at least 5 days. In the clinically directed strategy, the antibiotic was only initiated for clinical failures.
Primary outcomes were protocol-defined clinical failure and total antibiotic consumption. Non-inferiority margin was prespecified as 10%. Secondary outcomes were the length of hospital stay, total antivenom consumption, new-onset organ failure, bleeding requiring transfusion, death/need for surgical intervention and drug-related adverse events.
The trial was prematurely stopped due to the COVID-19 situation after randomising 66 patients-34 to clinically directed initiation and 32 to routine use arms. Russell's viper was the most common (21 (32%)) biting snake species identified; 52 (79%) patients had evidence of haemotoxic envenomation at baseline, and 24 (36%) patients developed AKI. There were 10 clinical failures-six in the clinically directed initiation arm and four in the routine use arm. The difference in clinical failure between the two arms was 5.2% (-12.0%-21.7%; p=0.291); the upper bound of the CI exceeded the prespecified non-inferiority margin. Total antibiotic consumption, expressed in DDDs, was significantly lower in the clinically directed initiation arm (0 (0-1) vs 5.31 (4.67-6.17); p<0.001). Three serious adverse events resulting in two deaths (one in each arm) were observed.
We could not demonstrate the non-inferiority of clinically directed initiation compared with routine use of amoxicillin-clavulanate among patients with local swelling caused by haemotoxic snakebites. However, the frequency of clinical failures was similar, and antibiotic consumption was substantially lower with the clinically directed initiation strategy.
ClinicalTrials.gov; NCT02570347.
尽管缺乏临床证据，但阿莫西林-克拉维酸仍常用于预防蛇咬伤后的感染。我们旨在证明，在这种情况下，临床指导下开始使用阿莫西林-克拉维酸并不逊于常规使用。
开放标签、随机、非劣效性试验，终点采用盲法判定。
印度南部一家教学医院的急诊科。
咬伤后24小时内出现局部肿胀的成年蛇咬伤患者。
在常规使用策略中，静脉注射后口服阿莫西林-克拉维酸至少5天。在临床指导策略中，仅在临床治疗失败时才开始使用抗生素。
主要结局为方案定义的临床治疗失败和抗生素总消耗量。非劣效性界限预先设定为10%。次要结局为住院时间、抗蛇毒血清总消耗量、新发器官衰竭、需要输血的出血、死亡/手术干预需求以及药物相关不良事件。
在将66例患者随机分组后，由于新冠疫情，试验提前终止，其中34例进入临床指导起始组，32例进入常规使用组。罗素蝰蛇是最常见的咬伤蛇种（21例（32%））；52例（79%）患者在基线时有血液毒性蛇毒中毒的证据，24例（36%）患者发生急性肾损伤。有10例临床治疗失败，临床指导起始组6例，常规使用组4例。两组临床治疗失败的差异为5.2%（-12.0%-21.7%；p=0.291）；置信区间上限超过预先设定的非劣效性界限。以限定日剂量表示的抗生素总消耗量，临床指导起始组显著更低（0（0-1）对比5.31（4.67-6.17）；p<0.001）。观察到3例严重不良事件，导致2例死亡（每组各1例）。
在血液毒性蛇咬伤引起局部肿胀的患者中，我们未能证明临床指导起始使用阿莫西林-克拉维酸与常规使用相比具有非劣效性。然而，临床治疗失败的频率相似，且临床指导起始策略的抗生素消耗量显著更低。
ClinicalTrials.gov；NCT02570347。
