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JAC Advance Access originally published online on May 25, 2009
Journal of Antimicrobial Chemotherapy 2009 64(2):388-391; doi:10.1093/jac/dkp171
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© The Author 2009. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. All rights reserved. For Permissions, please e-mail: journals.permissions@oxfordjournals.org

Original research

Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis

Won-Jung Koh1, O. Jung Kwon1, Hyesun Gwak2, Joo Won Chung3, Sang-Nae Cho4, Woo Sung Kim5 and Tae Sun Shim5,*

1 Division of Pulmonary and Critical Care Medicine, Department of Medicine, Samsung Medical Center, Sungkyunkwan University School of Medicine, Seoul, Korea 2 College of Pharmacy, Ewha Womans University, Seoul, Korea 3 Department of Pharmacy, Asan Medical Center, Seoul, Korea 4 Department of Microbiology, Yonsei University College of Medicine, Seoul, Korea 5 Division of Pulmonary and Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul, 138-736, Korea

Received 10 February 2009; returned 15 March 2009; revised 16 April 2009; accepted 16 April 2009

* Corresponding author. Tel: +82-2-3010-3892, Fax: +82-2-3010-6968, E-mail: shimts{at}amc.seoul.kr

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.

Keywords: MDR-TB , XDR-TB , oxazolidinones , efficacy , tolerability


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