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Correspondence |

How Should We Treat “Difficult” Multidrug-Resistant Tuberculosis? FREE TO VIEW

Wing Wai Yew, MB, FCCP; Chi Chiu Leung, MB, FCCP
Author and Funding Information

Affiliations: Tuberculosis and Chest Unit Grantham Hospital,  Tuberculosis and Chest Service Department of Health Hong Kong, People's Republic of China

Correspondence to: Wing Wai Yew, MB, FCCP, Tuberculosis and Chest Unit, Grantham Hospital, Wong Chuk Hang, Aberdeen, Hong Kong, People's Republic of China; e-mail: yewww@ha.org.hk


The authors have reported to the ACCP that no significant conflicts of interest exist with any companies/organizations whose products or services may be discussed in this article.

Reproduction of this article is prohibited without written permission from the American College of Chest Physicians (www.chestjournal.org/misc/reprints.shtml).


Chest. 2009;135(2):587-588. doi:10.1378/chest.08-1776
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To the Editor:

We read with great interest the case series elegantly reported by Condos and associates1 in the July issue of CHEST, regarding the good efficacy and reasonable tolerability of linezolid in the treatment of extensively drug-resistant tuberculosis. However, it appears that four of the six adult patients cited in the article were switched from a linezolid regimen of 600 mg twice daily to one of 600 mg once daily after the onset of drug-induced toxic effects, mainly hematologic ones. The relatively short half-life of linezolid, alongside its limited postantibiotic effect against Mycobacterium tuberculosis, would theoretically favor the use of a “standard” dosage of 600 mg twice daily to achieve the optimal therapeutic effect.2 Moreover, neurotoxicity might not be readily minimized even with once-daily dosing.3

In the last few years, we acquired preliminary experience regarding the efficacy of a limited duration (generally 2 to 3 months) for the initial administration of linezolid at this conventional dosing, on top of therapy with fluoroquinolones and other second-line antituberculosis drugs, in the long-term treatment of fluoroquinolone-resistant, multidrug-resistant tuberculosis.4 Linezolid, alongside other new agents such as TMC-207, PA-824, and OPC-67683, showed sterilizing activity against the bacillary persisters of bacillus Calmette-Guerin and/or M tuberculosis in the Wayne model (Kevin Pethe, PhD; personal communication, March 17, 2008). Similar activity was also demonstrated in the murine model of tuberculosis.

These observations might help to explain the possible efficacy of our current chemotherapy approach of adding linezolid to therapy only in the intensive phase. Such a strategy would potentially reduce toxicity and curtail the development of drug resistance during chemotherapy with the new agent in formidable drug resistance scenarios. It seems that further evaluation of this approach is warranted. Clearly, the judicious use of adjunctive surgery may also be indicated for select candidates,5 preferably during the window of opportunity, 3 to 6 months after the start of chemotherapy.

Condos R, Hadgiangelis N, Leibert E, et al. Case series report of a linezolid-containing regimen for extensively drug-resistant tuberculosis. Chest. 2008;134:187-192. [PubMed] [CrossRef]
 
Hui M, Au-Yeang C, Wong KT, et al. Post-antibiotic effects of linezolid and other agents againstMycobacterium tuberculosisInt J Antimicrob Agents. 2008;31:395-396. [PubMed]
 
Park IN, Hong SB, Oh YM, et al. Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006;58:701-704. [PubMed]
 
Yew WW, Chau CH, Wen KH. Linezolid in the treatment of “difficult” multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12:345-346. [PubMed]
 
Chan ED, Laurel V, Strand MJ, et al. Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2004;169:1103-1109. [PubMed]
 

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References

Condos R, Hadgiangelis N, Leibert E, et al. Case series report of a linezolid-containing regimen for extensively drug-resistant tuberculosis. Chest. 2008;134:187-192. [PubMed] [CrossRef]
 
Hui M, Au-Yeang C, Wong KT, et al. Post-antibiotic effects of linezolid and other agents againstMycobacterium tuberculosisInt J Antimicrob Agents. 2008;31:395-396. [PubMed]
 
Park IN, Hong SB, Oh YM, et al. Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother. 2006;58:701-704. [PubMed]
 
Yew WW, Chau CH, Wen KH. Linezolid in the treatment of “difficult” multidrug-resistant tuberculosis. Int J Tuberc Lung Dis. 2008;12:345-346. [PubMed]
 
Chan ED, Laurel V, Strand MJ, et al. Treatment and outcome analysis of 205 patients with multidrug-resistant tuberculosis. Am J Respir Crit Care Med. 2004;169:1103-1109. [PubMed]
 
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