Low-dosage ethambutol, less than 12.5 mg/kg/day, does not worsen the clinical outcomes of pulmonary Mycobacterium avium and Mycobacterium intracellulare disease: a retrospective cohort study

Infection. 2022 Aug;50(4):879-887. doi: 10.1007/s15010-022-01757-3. Epub 2022 Feb 1.

Abstract

Objectives: Multidrug chemotherapy is recommended for treating pulmonary Mycobacterium avium and Mycobacterium intracellulare disease. Although ethambutol has been demonstrated to inhibit macrolide resistance, the ethambutol dosage is sometimes decreased due to concerns about optic neuropathy. We aimed to assess whether lower ethambutol doses impact treatment outcomes.

Methods: Patients treated over 12 months between 2016 and 2020 were collected retrospectively. Clinical outcomes, including negative culture conversion, microbiological cure, adverse events, resistance to macrolides, and recurrence, were compared according to daily ethambutol dosage.

Results: Among 146 patients, 42 were treated with ethambutol dosages over 12.5 mg/kg/day, and 104 were treated with lower dosages. Negative culture conversion was achieved for 125 patients, and 90 patients achieved microbiological cure. Recurrence was identified in 16 patients who achieved microbiological cure. No macrolide resistance was observed, and no significant difference was observed in the percentage of negative culture conversion (P = 1.00) or microbiological cure (P = 0.67) between the high- and low-dosage ethambutol groups. Sputum smear positivity was associated with a lower adjusted odds ratio (aOR) of negative culture conversion (aOR: 0.48, 95% CI: 0.29-0.80). A lower aOR of microbiological cure was independently associated with sputum smear positivity (aOR: 0.52, 95% CI: 0.37-0.74) and with the use of an intermittent regimen (aOR: 0.60, 95% CI: 0.41-0.87). Daily ethambutol dosage was not identified as a prognostic factor for any of the outcomes. Optic neuropathy was observed in 7.1% of the high-dose ethambutol group and 1.0% of the low-dosage ethambutol group (P = 0.07).

Conclusion: An ethambutol dosage of 12.5 mg/kg/day or less in guideline-based chemotherapy may reduce optic neuropathy without worsening clinical outcomes.

Keywords: Cohort study; Dosage; Ethambutol; Mycobacteria.

MeSH terms

  • Anti-Bacterial Agents / therapeutic use
  • Antitubercular Agents / therapeutic use
  • Drug Therapy, Combination
  • Ethambutol / therapeutic use
  • Humans
  • Mycobacterium avium
  • Mycobacterium avium Complex
  • Mycobacterium avium-intracellulare Infection* / drug therapy
  • Mycobacterium avium-intracellulare Infection* / microbiology
  • Optic Nerve Diseases* / chemically induced
  • Optic Nerve Diseases* / drug therapy
  • Retrospective Studies
  • Rifampin / therapeutic use
  • Treatment Outcome

Substances

  • Anti-Bacterial Agents
  • Antitubercular Agents
  • Ethambutol
  • Rifampin