While erysipelas recurrence remain high, relapse rates have been shown to decrease using oral penicillin V or intramuscular benzathine penicillin. However, a significant number of patients encounter pain or contraindications to IM injections, and oral penicillin is no longer available in Belgium.

The objective of our study was to retrospectively analyze, in a non-comparative single-center cohort, the outcomes of patients with recurrent erysipelas having received amoxicillin (1 g/day) as an alternative prophylactic antibiotic.

Twenty-six patients were included. Mean age was 58.7 years, with male predominance (69.2%). The erysipelas incidence rate prior to amoxicillin prophylaxis was 4.5 episodes/patient-year. Following the introduction of amoxicillin prophylaxis, the incidence rate fell to 0.15 episode/patient-year ( p   <  0.001). Even though this represented a 66% reduction, the small sample size limits generalizability. Mean follow-up duration was 44.58 months. Amoxicillin was discontinued in 15 patients (57.7%), of whom eight (53.3%) relapsed. During amoxicillin treatment and after withdrawal, there occurred no severe side effect such as allergic reaction, gastrointestinal event, mycosis, Clostridioides difficile infection, or colonization or infection by multidrug-resistant bacteria.

This study suggests that at a preventive dose, amoxicillin is well-tolerated, reducing the incidence of erysipelas, possibly representing a viable therapeutic option for patients with contraindication, intolerance, or limited access to first-line prophylaxis (intramuscular or oral penicillin). Given the small sample size and the absence of a comparator arm, comparative studies are needed to confirm the potential equivalence of amoxicillin with penicillin V.