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Association Between Low-Dose Ethambutol Therapy and Optic Neuropathy in Mycobacterium avium Complex Pulmonary
Yasuhiro Morimoto1,2, Hiroki Matsui3,4, Masaki Ikeda1
1Department of Pulmonology, Kameda Medical Center, Kamogawa, Chiba, Japan.
Background:
Current guidelines recommend ethambutol as a first-line agent for treating Mycobacterium avium complex pulmonary disease (MAC-PD) but can induce optic neuropathy. Previous studies suggest that low-dose ethambutol may reduce the incidence of optic neuropathy without compromising its effectiveness, but have not adequately adjusted for risk factors for optic neuropathy. We investigated the association between low-dose ethambutol therapy and optic neuropathy in patients with MAC-PD.
Methods:
This retrospective cohort study included patients treated for MAC-PD at Kameda Medical Center between April 2003 and July 2024. Patients were categorized into low-dose (<12.5 mg/kg/day) and high-dose (≥12.5 mg/kg/day) ethambutol groups. The primary outcome was the incidence of optic neuropathy. Secondary outcomes included failure of negative culture conversion and macrolide resistance. Propensity score-based overlap weighting was used to adjust for patient characteristics and outcomes were compared using datasets generated through bootstrap resampling.
Results:
Of 223 patients, 79 received low-dose (10.7 mg/kg/day) and 144 received high-dose ethambutol (15.4 mg/kg/day). None of the patients in the low-dose group and 4.8% in the high-dose group developed optic neuropathy. After adjustment, the risk of optic neuropathy was significantly lower in the low-dose ethambutol group (risk difference: -17.1%, 95% CI: -32.9% to -5.4%), but the risk difference for failure of negative culture conversion and macrolide resistance did not differ significantly between groups (-20.0%, 95% CI: -45.6% to 2.5%; and -4.9%, 95% CI: -13.5% to 0.0%, respectively).
Conclusions:
Low-dose ethambutol therapy may reduce the risk of optic neuropathy without compromising treatment outcomes, offering a safer option for MAC-PD.
Insights
Low-dose ethambutol significantly reduces optic neuropathy risk in Mycobacterium avium complex pulmonary disease (MAC-PD) patients. This safer treatment option maintains comparable efficacy to higher doses.
Area of Science:
- Pulmonary Medicine
- Infectious Diseases
- Ophthalmology
Background:
- Current guidelines recommend ethambutol for Mycobacterium avium complex pulmonary disease (MAC-PD).
- Ethambutol can cause optic neuropathy, a significant side effect.
- Previous research suggests lower doses may mitigate optic neuropathy risk without impacting efficacy.
Purpose of the Study:
- To investigate the association between low-dose ethambutol therapy and optic neuropathy incidence in MAC-PD patients.
- To compare treatment outcomes, including negative culture conversion and macrolide resistance, between low-dose and high-dose ethambutol groups.
- To provide evidence for a potentially safer ethambutol dosing strategy for MAC-PD.
Main Methods:
- Retrospective cohort study of 223 MAC-PD patients treated between 2003 and 2024.
- Patients were divided into low-dose (<12.5 mg/kg/day) and high-dose (≥12.5 mg/kg/day) ethambutol groups.
- Propensity score weighting was employed to adjust for confounding factors, with bootstrap resampling for outcome comparison.
Main Results:
- None of the 79 patients on low-dose ethambutol developed optic neuropathy, compared to 4.8% of 144 patients on high-dose ethambutol.
- Adjusted analysis revealed a significantly lower risk of optic neuropathy in the low-dose group (risk difference: -17.1%).
- No significant differences were observed in failure of negative culture conversion or macrolide resistance between the groups.
Conclusions:
- Low-dose ethambutol therapy appears to be a safer option for treating MAC-PD.
- This approach may significantly reduce the incidence of ethambutol-induced optic neuropathy.
- Treatment outcomes regarding culture conversion and resistance are not compromised by using lower-dose ethambutol.
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