BACKGROUND: Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. METHODS: Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. RESULTS: The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268-443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233-405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26-145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298-427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48-160 days). CONCLUSIONS: A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.
BACKGROUND: Although previous studies have suggested that linezolid may be effective for treating multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB), the optimal dose of linezolid for intractable MDR/XDR-TB is not clear. METHODS: Twenty-four patients with intractable MDR/XDR-TB were treated with a daily 300 mg dose of linezolid as part of their anti-TB drug regimen. RESULTS: The patients were treated with linezolid for a median duration of 359 days [interquartile range (IQR) 268-443 days]. Seventeen (71%) patients received 300 mg of linezolid once daily from the beginning of treatment for a median duration of 289 days (IQR 233-405 days). Of these patients, four developed peripheral neuropathy, one of whom discontinued linezolid. In seven (29%) patients, 600 mg/day linezolid was administered initially for a median duration of 104 days (IQR 26-145 days) followed by 300 mg/day linezolid for a median duration of 348 days (IQR 298-427 days). In five of these seven patients, the reason for changing from 600 to 300 mg/day was due to side effects of 600 mg/day linezolid (peripheral neuropathy in four patients and leucopenia in one patient). After reducing the dose to 300 mg/day, linezolid could be continued in six of the seven patients. Negative sputum conversion was achieved in 22 (92%) patients after a median of 89 days from the start of linezolid treatment (IQR 48-160 days). CONCLUSIONS: A daily 300 mg dose of linezolid may be useful for increasing the chances of culture conversion in the treatment of patients with intractable MDR/XDR-TB and might have fewer side effects, especially neurotoxicity, compared with a daily 600 mg dose of linezolid therapy. The present results encourage further research into the use of a 300 mg dose of linezolid for MDR/XDR-TB patients.
Authors: Mathieu S Bolhuis; Richard van Altena; Donald R A Uges; Tjip S van der Werf; Jos G W Kosterink; Jan-Willem C Alffenaar Journal: Antimicrob Agents Chemother Date: 2010-09-13 Impact factor: 5.191
Authors: Myungsun Lee; Jongseok Lee; Matthew W Carroll; Hongjo Choi; Seonyeong Min; Taeksun Song; Laura E Via; Lisa C Goldfeder; Eunhwa Kang; Boyoung Jin; Hyeeun Park; Hyunkyung Kwak; Hyunchul Kim; Han-Seung Jeon; Ina Jeong; Joon Sung Joh; Ray Y Chen; Kenneth N Olivier; Pamela A Shaw; Dean Follmann; Sun Dae Song; Jong-Koo Lee; Dukhyoung Lee; Cheon Tae Kim; Veronique Dartois; Seung-Kyu Park; Sang-Nae Cho; Clifton E Barry Journal: N Engl J Med Date: 2012-10-18 Impact factor: 91.245