Clinically directed initiation versus routine use of amoxicillin-clavulanate and the risk of local complications among patients with haemotoxic snakebite envenomation treated at a teaching hospital in southern India: a randomised, non-inferiority trial.

Publication date: Jun 23, 2025

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

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Concepts Keywords
Antibiotic Adult
Hospital Amoxicillin-Potassium Clavulanate Combination
Snakebite Amoxicillin-Potassium Clavulanate Combination
Anti-Bacterial Agents
Anti-Bacterial Agents
Antivenins
Antivenins
Female
Hospitals, Teaching
Humans
India
Length of Stay
Male
Middle Aged
Randomized Controlled Trial
Snake Bites
TOXICOLOGY
Tropical medicine
Young Adult

Semantics

Type Source Name
drug DRUGBANK Amoxicillin
drug DRUGBANK Clavulanic acid
disease MESH complications
disease MESH infections
disease MESH Emergency
disease MESH bleeding
disease MESH death
disease IDO intervention
disease MESH COVID-19
disease MESH shock
disease IDO blood
disease IDO infection
disease MESH osteomyelitis
disease MESH pneumonia
disease MESH urinary tract infections

Original Article

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