Linezolid for Treatment of Chronic Extensively Drug-Resistant Tuberculosis

被引：458

作者：

Lee, Myungsun ^{[2
]}

Lee, Jongseok ^{[2
]}

Carroll, Matthew W. ^{[1
]}

Choi, Hongjo ^{[2
]}

Min, Seonyeong ^{[2
]}

Song, Taeksun ^{[2
]}

Via, Laura E. ^{[1
]}

Goldfeder, Lisa C. ^{[1
]}

Kang, Eunhwa ^{[2
]}

Jin, Boyoung ^{[2
]}

Park, Hyeeun ^{[2
]}

Kwak, Hyunkyung ^{[2
]}

Kim, Hyunchul ^{[2
]}

Jeon, Han-Seung ^{[2
]}

Jeong, Ina ^{[3
]}

Joh, Joon Sung ^{[3
]}

Chen, Ray Y. ^{[10
]}

Olivier, Kenneth N. ^{[9
]}

Shaw, Pamela A. ^{[11
]}

Follmann, Dean ^{[11
]}

Song, Sun Dae ^{[2
]}

Lee, Jong-Koo ^{[4
]}

Lee, Dukhyoung ^{[5
]}

Kim, Cheon Tae ^{[6
]}

Dartois, Veronique ^{[12
]}

Park, Seung-Kyu ^{[6
]}

Cho, Sang-Nae ^{[7
,8
]}

Barry, Clifton E., III ^{[1
]}

机构：

[1] NIAID, TB Res Sect, NIH, Bethesda, MD 20892 USA

[2] Int TB Res Ctr, Chang Won, South Korea

[3] Natl Med Ctr, Dept Internal Med, Seoul, South Korea

[4] Seoul Natl Univ Hosp, Dept Family Med, Seoul 110744, South Korea

[5] Korea Ctr Dis Control & Prevent, Osong, South Korea

[6] Natl Masan Hosp, Masan, South Korea

[7] Yonsei Univ, Coll Med, Dept Microbiol, Seoul, South Korea

[8] Yonsei Univ, Coll Med, Inst Immunol & Immunol Dis, Seoul, South Korea

[9] NIAID, Immunopathol Sect, NIH, Bethesda, MD 20892 USA

[10] NIAID, Lab Clin Infect Dis, Off Global Res, NIH, Bethesda, MD 20892 USA

[11] NIAID, Biostat Res Branch, NIH, Bethesda, MD 20892 USA

[12] Novartis Inst Trop Dis, Singapore, Singapore

来源：

NEW ENGLAND JOURNAL OF MEDICINE | 2012年 / 367卷 / 16期

基金：

美国国家卫生研究院;

关键词：

INTRACTABLE MULTIDRUG-RESISTANT; MYCOBACTERIUM-TUBERCULOSIS; PULMONARY TUBERCULOSIS; OXAZOLIDINONE ANTIBACTERIAL; MURINE MODEL; PHARMACOKINETICS; TOLERABILITY; MOXIFLOXACIN; OFLOXACIN; EFFICACY;

D O I：

10.1056/NEJMoa1201964

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

BACKGROUND Linezolid has antimycobacterial activity in vitro and is increasingly used for patients with highly drug-resistant tuberculosis. METHODS We enrolled 41 patients who had sputum-culture-positive extensively drug-resistant (XDR) tuberculosis and who had not had a response to any available chemotherapeutic option during the previous 6 months. Patients were randomly assigned to linezolid therapy that started immediately or after 2 months, at a dose of 600 mg per day, without a change in their background regimen. The primary end point was the time to sputum-culture conversion on solid medium, with data censored 4 months after study entry. After confirmed sputum-smear conversion or 4 months (whichever came first), patients underwent a second randomization to continued linezolid therapy at a dose of 600 mg per day or 300 mg per day for at least an additional 18 months, with careful toxicity monitoring. RESULTS By 4 months, 15 of the 19 patients (79%) in the immediate-start group and 7 of the 20 (35%) in the delayed-start group had culture conversion (P = 0.001). Most patients (34 of 39 [87%]) had a negative sputum culture within 6 months after linezolid had been added to their drug regimen. Of the 38 patients with exposure to linezolid, 31 (82%) had clinically significant adverse events that were possibly or probably related to linezolid, including 3 patients who discontinued therapy. Patients who received 300 mg per day after the second randomization had fewer adverse events than those who continued taking 600 mg per day. Thirteen patients completed therapy and have not had a relapse. Four cases of acquired resistance to linezolid have been observed. CONCLUSIONS Linezolid is effective at achieving culture conversion among patients with treatment-refractory XDR pulmonary tuberculosis, but patients must be monitored carefully for adverse events. (Funded by the National Institute of Allergy and Infectious Diseases and the Ministry of Health and Welfare, South Korea; ClinicalTrials.gov number, NCT00727844.)

引用

页码：1508 / 1518

页数：11

共 45 条

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