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Lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for Mycobacterium avium complex pulmonary disease
Institution:1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;2. Department of Radiology, Kanagawa Cardiovascular and Respiratory Center, Yokohama, Japan;1. Department of Respiratory Medicine, Kanagawa Cardiovascular and Respiratory Center 6-16-1 Tomioka-Higashi, Kanazawa-ku, Yokohama City, Kanagawa 236-0051, Japan;2. Department of Respiratory Medicine, Kumamoto University Hospital, Faculty of Life Sciences, Kumamoto University, 1-1-1 Honjo, Chuo-ku, Kumamoto 860-8556, Japan;1. Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishiku, Kitakyushu City, Fukuoka, 807-8555, Japan;2. Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8501, Japan;1. Department of Respiratory Medicine, Tobata Kyoritsu Hospital, 2-5-1 Sawami, Tobata-ku, Kitakyushu City, Fukuoka, 804-0093, Japan;2. Department of Respiratory Medicine, University of Occupational and Environmental Health, 1-1 Iseigaoka, Yahatanishi-ku, Kitakyushu City, Fukuoka, 807-8556, Japan;3. Department of Rehabilitation, Tobata Kyoritsu Hospital, 2-5-1 Sawami, Tobata-ku, Kitakyushu City, Fukuoka, 804-0093, Japan;4. Department of Respiratory Medicine, Unit of Translational Medicine, Nagasaki University Graduate School of Biomedical Sciences, 1-7-1 Sakamoto, Nagasaki City, Nagasaki, 852-8001, Japan
Abstract:BackgroundEthambutol ocular toxicity is a major problem during combination chemotherapy for Mycobacterium avium complex (MAC) pulmonary disease (MAC-PD) due to years-long therapy for MAC.ObjectivesThis study aimed to identify the lower dose of daily ethambutol that can reduce ocular toxicity.MethodsWe retrospectively reviewed the medical records of 312 patients who visited The University of Tokyo Hospital between January 2007 and December 2017 for nontuberculous mycobacterial pulmonary disease. Seventy-six patients with MAC-PD who were treated with combination chemotherapy for the first time were analyzed in this study.ResultsEthambutol was discontinued because of visual symptoms in 13 patients (17%), 7 of whom were diagnosed with ethambutol ocular neuropathy. The dose per body weight was significantly higher in patients who developed ocular neuropathy than in those who did not (15.4 mg/kg/d vs. 12.5 mg/kg/d, respectively; p = 0.048). We assigned patients to higher or lower dose groups according to the median dose of 12.5 mg/kg/d. Although ocular neuropathy developed in 6 out of 38 patients in the higher dose group, ocular neuropathy developed in 1 out of 38 patients in the lower dose group (16% vs. 3%, respectively; p = 0.038). The failures of sputum culture conversion and radiological improvement were not significantly different between the two groups (p = 0.638 and 0.305, respectively). Macrolide resistance developed in one patient per group during follow-up (3% per group, p = 0.945).ConclusionsA lower dose of ethambutol may reduce ocular toxicity without radiological deterioration for pulmonary MAC infection.
Keywords:Ethambutol  Toxicity  Ocular neuropathy  Lower dose therapy  ATS"}  {"#name":"keyword"  "$":{"id":"kwrd0040"}  "$$":[{"#name":"text"  "_":"American Thoracic Society  CLR"}  {"#name":"keyword"  "$":{"id":"kwrd0050"}  "$$":[{"#name":"text"  "_":"clarithromycin  CT"}  {"#name":"keyword"  "$":{"id":"kwrd0060"}  "$$":[{"#name":"text"  "_":"computed tomography  eGFR"}  {"#name":"keyword"  "$":{"id":"kwrd0070"}  "$$":[{"#name":"text"  "_":"estimated glomerular filtration rate  EMB"}  {"#name":"keyword"  "$":{"id":"kwrd0080"}  "$$":[{"#name":"text"  "_":"ethambutol  IQR"}  {"#name":"keyword"  "$":{"id":"kwrd0090"}  "$$":[{"#name":"text"  "_":"interquartile range  MAC"}  {"#name":"keyword"  "$":{"id":"kwrd0100"}  "$$":[{"#name":"text"  "$$":[{"#name":"italic"  "_":"Mycobacterium avium"}  {"#name":"__text__"  "_":" complex  MAC-PD"}  {"#name":"keyword"  "$":{"id":"kwrd0110"}  "$$":[{"#name":"text"  "$$":[{"#name":"italic"  "_":"Mycobacterium avium"}  {"#name":"__text__"  "_":" complex pulmonary disease  NTM"}  {"#name":"keyword"  "$":{"id":"kwrd0120"}  "$$":[{"#name":"text"  "_":"nontuberculous mycobacterium  RFP"}  {"#name":"keyword"  "$":{"id":"kwrd0130"}  "$$":[{"#name":"text"  "_":"rifampicin  SD"}  {"#name":"keyword"  "$":{"id":"kwrd0140"}  "$$":[{"#name":"text"  "_":"standard deviation
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