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Erschienen in: Infection 4/2022

01.02.2022 | Original Paper

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

verfasst von: Fumiya Watanabe, Shota Kaburaki, Koji Furuuchi, Fumiko Uesugi, Keiji Fujiwara, Yoshiaki Tanaka, Takashi Yoshiyama, Yuji Shiraishi, Atsuyuki Kurashima, Ken Ohta, Kazuhiko Hanada, Kozo Morimoto

Erschienen in: Infection | Ausgabe 4/2022

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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.
Literatur
1.
Zurück zum Zitat Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56(1):2000535.CrossRef Daley CL, Iaccarino JM, Lange C, Cambau E, Wallace RJ Jr, Andrejak C, et al. Treatment of nontuberculous mycobacterial pulmonary disease: an official ATS/ERS/ESCMID/IDSA clinical practice guideline. Eur Respir J. 2020;56(1):2000535.CrossRef
2.
Zurück zum Zitat Namkoong H, Kurashima A, Morimoto K, Hoshino Y, Hasegawa N, Ato M, et al. Epidemiology of pulmonary nontuberculous mycobacterial disease. Japan Emerg Infect Dis. 2016;22(6):1116–7.CrossRef Namkoong H, Kurashima A, Morimoto K, Hoshino Y, Hasegawa N, Ato M, et al. Epidemiology of pulmonary nontuberculous mycobacterial disease. Japan Emerg Infect Dis. 2016;22(6):1116–7.CrossRef
3.
Zurück zum Zitat Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: clinicians’ perspectives. Tuberc Respir Dis (Seoul). 2016;79(2):74–84.CrossRef Ryu YJ, Koh WJ, Daley CL. Diagnosis and treatment of nontuberculous mycobacterial lung disease: clinicians’ perspectives. Tuberc Respir Dis (Seoul). 2016;79(2):74–84.CrossRef
4.
Zurück zum Zitat Nair VS, LeBrun M, Kass I. Peripheral neuropathy associated with ethambutol. Chest. 1980;77(1):98–100.CrossRef Nair VS, LeBrun M, Kass I. Peripheral neuropathy associated with ethambutol. Chest. 1980;77(1):98–100.CrossRef
5.
Zurück zum Zitat Kass JS, Shandera WX. Nervous system effects of antituberculosis therapy. CNS Drugs. 2010;24(8):655–67.CrossRef Kass JS, Shandera WX. Nervous system effects of antituberculosis therapy. CNS Drugs. 2010;24(8):655–67.CrossRef
6.
Zurück zum Zitat Griffith DE, Brown-Elliott BA, Shepherd S, McLarty J, Griffith L, Wallace RJ Jr. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2005;172(2):250–3.CrossRef Griffith DE, Brown-Elliott BA, Shepherd S, McLarty J, Griffith L, Wallace RJ Jr. Ethambutol ocular toxicity in treatment regimens for Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2005;172(2):250–3.CrossRef
7.
Zurück zum Zitat Nash KA. Effect of drug concentration on emergence of macrolide resistance in Mycobacterium avium. Antimicrob Agents Chemother. 2001;45(6):1607–14.CrossRef Nash KA. Effect of drug concentration on emergence of macrolide resistance in Mycobacterium avium. Antimicrob Agents Chemother. 2001;45(6):1607–14.CrossRef
8.
Zurück zum Zitat Bermudez LE, Nash KA, Petrofsky M, Young LS, Inderlied CB. Effect of ethambutol on emergence of clarithromycin-resistant Mycobacterium avium complex in the beige mouse model. J Infect Dis. 1996;174(6):1218–22.CrossRef Bermudez LE, Nash KA, Petrofsky M, Young LS, Inderlied CB. Effect of ethambutol on emergence of clarithromycin-resistant Mycobacterium avium complex in the beige mouse model. J Infect Dis. 1996;174(6):1218–22.CrossRef
9.
Zurück zum Zitat Griffith DE, Brown-Elliott BA, Langsjoen B, Zhang Y, Pan X, Girard W, et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2006;174(8):928–34.CrossRef Griffith DE, Brown-Elliott BA, Langsjoen B, Zhang Y, Pan X, Girard W, et al. Clinical and molecular analysis of macrolide resistance in Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2006;174(8):928–34.CrossRef
10.
Zurück zum Zitat Kim HJ, Lee JS, Kwak N, Cho J, Lee CH, Han SK, et al. Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease. BMC Pulm Med. 2019;19(1):212.CrossRef Kim HJ, Lee JS, Kwak N, Cho J, Lee CH, Han SK, et al. Role of ethambutol and rifampicin in the treatment of Mycobacterium avium complex pulmonary disease. BMC Pulm Med. 2019;19(1):212.CrossRef
11.
Zurück zum Zitat Dubé MP, Sattler FR, Torriani FJ, See D, Havlir DV, Kemper CA, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis. 1997;176(5):1225–32.CrossRef Dubé MP, Sattler FR, Torriani FJ, See D, Havlir DV, Kemper CA, et al. A randomized evaluation of ethambutol for prevention of relapse and drug resistance during treatment of Mycobacterium avium complex bacteremia with clarithromycin-based combination therapy. California Collaborative Treatment Group. J Infect Dis. 1997;176(5):1225–32.CrossRef
12.
Zurück zum Zitat Morimoto K, Namkoong H, Hasegawa N, Nakagawa T, Morino E, Shiraishi Y, Nontuberculous Mycobacteriosis Japan Research Consortium, et al. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc. 2016;13(11):1904–11.CrossRef Morimoto K, Namkoong H, Hasegawa N, Nakagawa T, Morino E, Shiraishi Y, Nontuberculous Mycobacteriosis Japan Research Consortium, et al. Macrolide-resistant Mycobacterium avium complex lung disease: analysis of 102 consecutive cases. Ann Am Thorac Soc. 2016;13(11):1904–11.CrossRef
13.
Zurück zum Zitat Kwon YS, Kwon BS, Kim OH, Park YE, Shim TS, Chong YP, et al. Treatment outcomes after discontinuation of ethambutol due to adverse events in Mycobacterium avium complex lung disease. J Korean Med Sci. 2020;35(9):e59.CrossRef Kwon YS, Kwon BS, Kim OH, Park YE, Shim TS, Chong YP, et al. Treatment outcomes after discontinuation of ethambutol due to adverse events in Mycobacterium avium complex lung disease. J Korean Med Sci. 2020;35(9):e59.CrossRef
14.
Zurück zum Zitat Fraunfelder FW, Sadun AA, Wood T. Update on ethambutol optic neuropathy. Expert Opin Drug Saf. 2006;5(5):615–8.CrossRef Fraunfelder FW, Sadun AA, Wood T. Update on ethambutol optic neuropathy. Expert Opin Drug Saf. 2006;5(5):615–8.CrossRef
15.
Zurück zum Zitat Citron KM, Thomas GO. Ocular toxicity from ethambutol. Thorax. 1986;41(10):737–9.CrossRef Citron KM, Thomas GO. Ocular toxicity from ethambutol. Thorax. 1986;41(10):737–9.CrossRef
16.
Zurück zum Zitat Chan RY, Kwok AK. Ocular toxicity of ethambutol. Hong Kong Med J. 2006;12(1):56–60.PubMed Chan RY, Kwok AK. Ocular toxicity of ethambutol. Hong Kong Med J. 2006;12(1):56–60.PubMed
17.
Zurück zum Zitat Ando T, Kage H, Matsumoto Y, Zokumasu K, Nagase T. Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease. Respir Investig. 2021;S2212–5345(21):00121. Ando T, Kage H, Matsumoto Y, Zokumasu K, Nagase T. Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease. Respir Investig. 2021;S2212–5345(21):00121.
18.
Zurück zum Zitat van Ingen J, Aksamit T, Andrejak C, Böttger EC, Cambau E, Daley CL, for NTM-NET, et al. Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement. Eur Respir J. 2018;51(3):1800170.CrossRef van Ingen J, Aksamit T, Andrejak C, Böttger EC, Cambau E, Daley CL, for NTM-NET, et al. Treatment outcome definitions in nontuberculous mycobacterial pulmonary disease: an NTM-NET consensus statement. Eur Respir J. 2018;51(3):1800170.CrossRef
19.
Zurück zum Zitat Lee BY, Kim S, Hong Y, Lee SD, Kim WS, Kim DS, et al. Risk factors for recurrence after successful treatment of Mycobacterium avium complex lung disease. Antimicrob Agents Chemother. 2015;59(6):2972–7.CrossRef Lee BY, Kim S, Hong Y, Lee SD, Kim WS, Kim DS, et al. Risk factors for recurrence after successful treatment of Mycobacterium avium complex lung disease. Antimicrob Agents Chemother. 2015;59(6):2972–7.CrossRef
20.
Zurück zum Zitat Jeong BH, Jeon K, Park HY, Kim SY, Lee KS, Huh HJ, et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2015;191(1):96–103.CrossRef Jeong BH, Jeon K, Park HY, Kim SY, Lee KS, Huh HJ, et al. Intermittent antibiotic therapy for nodular bronchiectatic Mycobacterium avium complex lung disease. Am J Respir Crit Care Med. 2015;191(1):96–103.CrossRef
21.
Zurück zum Zitat Kwak N, Park J, Kim E, Lee CH, Han SK, Yim JJ. Treatment outcomes of Mycobacterium avium complex lung disease: a systematic review and meta-analysis. Clin Infect Dis. 2017;65(7):1077–84.CrossRef Kwak N, Park J, Kim E, Lee CH, Han SK, Yim JJ. Treatment outcomes of Mycobacterium avium complex lung disease: a systematic review and meta-analysis. Clin Infect Dis. 2017;65(7):1077–84.CrossRef
22.
Zurück zum Zitat Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J. 2017;50(3):1602503.CrossRef Koh WJ, Moon SM, Kim SY, Woo MA, Kim S, Jhun BW, et al. Outcomes of Mycobacterium avium complex lung disease based on clinical phenotype. Eur Respir J. 2017;50(3):1602503.CrossRef
23.
Zurück zum Zitat Wallace RJ Jr, Brown-Elliott BA, McNulty S, Philley JV, Killingley J, Wilson RW, et al. Macrolide/Azalide therapy for nodular/bronchiectatic Mycobacterium avium complex lung disease. Chest. 2014;146(2):276–82.CrossRef Wallace RJ Jr, Brown-Elliott BA, McNulty S, Philley JV, Killingley J, Wilson RW, et al. Macrolide/Azalide therapy for nodular/bronchiectatic Mycobacterium avium complex lung disease. Chest. 2014;146(2):276–82.CrossRef
24.
Zurück zum Zitat Nakagawa T, Hashimoto H, Yagi M, Kogure Y, Sekimizu M, Saito AM, et al. Multicenter, open label, randomized controlled trial comparing intermittent versus daily treatment for noncavitary nodular/bronchiectatic Mycobacterium avium complex lung disease with rifampicin, ethambutol and clarithromycin (iREC): study protocol. BMJ Open Respir Res. 2019;6(1):e000434.CrossRef Nakagawa T, Hashimoto H, Yagi M, Kogure Y, Sekimizu M, Saito AM, et al. Multicenter, open label, randomized controlled trial comparing intermittent versus daily treatment for noncavitary nodular/bronchiectatic Mycobacterium avium complex lung disease with rifampicin, ethambutol and clarithromycin (iREC): study protocol. BMJ Open Respir Res. 2019;6(1):e000434.CrossRef
25.
Zurück zum Zitat Min J, Park J, Lee YJ, Kim SJ, Park JS, Cho YJ, Yoon HI, Lee CT, Lee JH. Determinants of recurrence after successful treatment of Mycobacterium avium complex lung disease. Int J Tuberc Lung Dis. 2015;19(10):1239–45.CrossRef Min J, Park J, Lee YJ, Kim SJ, Park JS, Cho YJ, Yoon HI, Lee CT, Lee JH. Determinants of recurrence after successful treatment of Mycobacterium avium complex lung disease. Int J Tuberc Lung Dis. 2015;19(10):1239–45.CrossRef
26.
Zurück zum Zitat Furuuchi K, Morimoto K, Kurashima A, Fujiwara K, Nakamoto K, Tanaka Y, et al. Treatment duration and disease recurrence following the successful treatment of patients with Mycobacterium avium complex lung disease. Chest. 2020;157(6):1442–5.CrossRef Furuuchi K, Morimoto K, Kurashima A, Fujiwara K, Nakamoto K, Tanaka Y, et al. Treatment duration and disease recurrence following the successful treatment of patients with Mycobacterium avium complex lung disease. Chest. 2020;157(6):1442–5.CrossRef
Metadaten
Titel
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
verfasst von
Fumiya Watanabe
Shota Kaburaki
Koji Furuuchi
Fumiko Uesugi
Keiji Fujiwara
Yoshiaki Tanaka
Takashi Yoshiyama
Yuji Shiraishi
Atsuyuki Kurashima
Ken Ohta
Kazuhiko Hanada
Kozo Morimoto
Publikationsdatum
01.02.2022
Verlag
Springer Berlin Heidelberg
Erschienen in
Infection / Ausgabe 4/2022
Print ISSN: 0300-8126
Elektronische ISSN: 1439-0973
DOI
https://doi.org/10.1007/s15010-022-01757-3

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