© 2007 American Thoracic Society
Toward Optimizing Treatment for Mycobacterium avium Complex Lung DiseaseTo the Editor:Griffith and coworkers in their recent article showed, by combining data from several noncomparative trials of Mycobacterium avium complex (MAC) lung disease, that adding ethambutol and rifamycin to a macrolide reduced the odds of macrolide resistance (1). Such an unusual approach is understandable, given the scarcity of data from randomized controlled trials. The magnitude of odds ratios adjusted by treatment regimens (see Table 1) might also provide assurance against effects of uncontrolled confounding by patient or disease characteristics.
Notwithstanding the higher cure rate with addition of surgery, only 16 out of 51 patients with macrolide-resistant MAC lung disease were operated upon. With the small numbers of subjects amenable to surgery, selection bias was likely, as rightly admitted. This result also highlights the importance of preventing macrolide resistance in the treatment of MAC disease. Although Griffith and coworkers did not provide data for evaluating the relative roles of ethambutol and rifamycin in the triple therapy for MAC lung disease (1), inference was possible from previous studies. A randomized placebo-controlled trial in disseminated MAC disease showed that ethambutol improved treatment efficacy of clarithromycin, whereas the addition of rifabutin to ethambutol and clarithromycin reduced the risk of acquiring macrolide resistance without affecting efficacy (2). Ethambutol is probably important for enabling the adjunctive role of rifamycin. The minimal inhibitory and bactericidal concentrations of rifamycin for M. avium complex were reduced in the presence of ethambutol (3). Despite the essential role of ethambutol for managing MAC disease, visual and renal impairment are relatively common problems with its use among the elderly population. There is no clinical evidence to support the practice of substituting fluoroquinolone for ethambutol. While thrice-weekly treatment compared with daily treatment may reduce the dose-dependent risk of ocular toxicity due to ethambutol (4), further dosage adjustment may still be necessary in case of considerable renal impairment. Unfortunately, there is no consensus for modifying the dosage of ethambutol according to creatinine clearance. While the American Thoracic Society (ATS), Centers for Disease Control and Prevention, and Infectious Diseases Society of America (IDSA) recommended dosage reduction for creatinine clearance below 30 ml/min (5), other authorities recommended modification for creatinine clearance below 50 ml/min (6). Further studies are warranted to strike the best balance between efficacy and toxicity.
Department of Health, Hong Kong, China FOOTNOTES Conflict of Interest Statement: None of the authors has a financial relationship with a commercial entity that has an interest in the subject of this manuscript. REFERENCES
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