Amoxicillin/Clavulanic Acid for the Treatment of Odontogenic Infections: A Randomised Study Comparing Efficacy and Tolerability versus Clindamycin

Abstract

Background. Treatment of odontogenic infections includes surgical drainage and adjunctive antibiotics. This study was designed to generate efficacy and safety data to support twice daily dosing of amoxicillin/clavulanic acid compared to clindamycin in odontogenic infections. Methods. This was a phase IV, randomised, observer blind study; 472 subjects were randomised to receive amoxicillin/clavulanic acid (875 mg/125 mg BID, n = 235) or clindamycin (150 mg QID, n = 237) for 5 or 7 days based on clinical response. The primary endpoint was percentage of subjects achieving clinical success (composite measure of pain, swelling, fever, and additional antimicrobial therapy required) at the end of treatment. Results. The upper limit of two-sided 95% confidence interval for the treatment difference between the study arms (7.7%) was within protocol specified noninferiority margin of 10%, thus demonstrating noninferiority of amoxicillin/clavulanic acid to clindamycin. Secondary efficacy results showed a higher clinical success rate at Day 5 in the amoxicillin/clavulanic acid arm. Most adverse events (raised liver enzymes, diarrhoea, and headache) were similar across both arms and were of mild to moderate intensity. Conclusion. Amoxicillin/clavulanic acid was comparable to clindamycin in achieving clinical success (88.2% versus 89.7%) in acute odontogenic infections and the safety profile was consistent with the known side effects of both drugs. Trial Registration. This trial is registered with Clinicaltrials.gov identifier: NCT02141217.

Figure 1

Study schema. Note: the study had a 1-day screening period (Day 1 to Day 0) during which eligibility was assessed and laboratory tests were performed. Randomisation occurred within 24 hours of screening at baseline (Day 0). Further visits (Day 2, Day 5, and Day 7) were calculated from the baseline/randomisation visit (Day 0).

Figure 2

Scatter plot of LFT with respect to baseline and end of study by treatment. Normalised value = laboratory value/upper limit of normal reference range of the respective local laboratory.