Efficacy and tolerability of daily-half dose linezolid in patients with intractable multidrug-resistant tuberculosis.
OBJECTIVE
Although linezolid has good in vitro activity against Mycobacterium tuberculosis, its long-term use in the treatment of multidrug-resistant tuberculosis (MDR-TB) may be limited by its cost and serious adverse reactions. We therefore evaluated the efficacy and tolerability of a reduced dose of linezolid, in combination with other anti-TB drugs, in patients with intractable or extensive MDR-TB.


METHODS
MDR-TB patients unresponsive to at least three cycles of treatment were treated with daily-half doses of linezolid (600 mg once per day) plus at least four companion drugs.


RESULTS
As of March 2006, eight patients, all HIV-negative, had been treated with linezolid for 3-18 months. Cultures became negative in all patients in an average of 82 days. Four patients developed peripheral neuropathy, two developed optic neuropathy and one developed anaemia. Although optic neuropathy resolved after cessation of linezolid therapy, peripheral neuropathy continued. One patient completed 18 months of linezolid therapy. Two patients, who have taken linezolid for 15-17 months, are still on treatment and remain in culture conversion. Three patients stopped linezolid after 7-9 months, two because of side effects and one for economic reasons, but remain on treatment with other second-line drugs with culture conversion. Two patients died from severe respiratory failure, but both previously had shown culture conversion.


CONCLUSIONS
Although daily-half doses of linezolid were effective in patients with intractable or extensive MDR-TB, this dosage regimen did not reduce long-term use-related side effects, such as peripheral and optic neuropathy.
Park
I-Nae
IN
Division of Pulmonary & Critical Care Medicine, University of Ulsan College of Medicine, Asan Medical Center, 388-1 Pungnap-dong, Songpa-gu, Seoul, Korea.
Hong
Sang-Bum
SB
Oh
Yeon-Mok
YM
Kim
Mi-Na
MN
Lim
Chae-Man
CM
Lee
Sang Do
SD
Koh
Younsuck
Y
Kim
Woo Sung
WS
Kim
Dong Soon
DS
Kim
Won Dong
WD
Shim
Tae Sun
TS
D000081:Acetamides / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D004305:Dose-Response Relationship, Drug; D004334:Drug Administration Schedule; D024901:Drug Resistance, Multiple, Bacterial / Q000187:drug effects; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000302:isolation & purification; D023303:Oxazolidinones / Q000008:administration & dosage / Q000009:adverse effects / Q000627:therapeutic use*; D016896:Treatment Outcome; D014397:Tuberculosis, Pulmonary / Q000188:drug therapy* / Q000382:microbiology
D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid