Desensitisation protocol for ethambutol in the treatment of Mycobacterium avium complex pulmonary disease

Background Ethambutol is a key component of treatment for Mycobacterium avium complex pulmonary disease (MAC-PD), primarily through suppression of macrolide resistance. However, adverse drug reactions frequently lead to treatment interruption, and evidence-based alternatives remain limited. We evaluated the feasibility and outcomes of a structured outpatient ethambutol desensitisation protocol in patients with MAC-PD who developed ethambutol intolerance or hypersensitivity. Methods We conducted a multicentre observational study across four specialist NTM centres. Patients undergoing treatment for MAC-PD who experienced an ethambutol-related adverse reaction leading to drug cessation were eligible. A patient-led outpatient desensitisation protocol commenced at 25 mg daily with gradual dose escalation to a weight-based target dose. The protocol allowed temporary dose reduction to previously tolerated levels if symptoms recurred. Success was defined as achievement of the target dose or maintenance of a tolerated dose associated with sustained culture conversion. Results Twenty desensitisation episodes were performed in 17 patients (65% female; mean age 72 years). The most common indication was rash (70%), followed by headache (15%). Overall, 17/20 (85%) desensitisations were successful, including 13/14 (93%) among patients with delayed cutaneous reactions. Mean time to target dose was 9 weeks (median 4 weeks). No severe immediate hypersensitivity reactions occurred during desensitisation. Sixteen episodes (80%) were associated with culture conversion, and 11 (55%) patients completed therapy with ethambutol-containing regimens. Conclusions Outpatient ethambutol desensitisation appears feasible, safe and effective in selected patients with MAC-PD and non-severe ethambutol intolerance. This approach may help preserve an essential component of MAC therapy when treatment options are otherwise limited.