Linezolid use for treatment of multidrug-resistant and extensively drug-resistant tuberculosis, New York City, 2000-06.
Rationale Linezolid may be effective for the treatment of multidrug-resistant (MDR) and extensively drug-resistant (XDR) tuberculosis (TB); however, serious adverse events are common and there is little information on the management of these toxicities.


METHODS
We retrospectively reviewed public health and medical records of 16 MDR TB patients, including 10 patients with XDR TB, who were treated with linezolid in New York City between January 2000 and December 2006, to determine treatment outcomes and describe the incidence, management and predictors of adverse events.


RESULTS
Linezolid was added to MDR TB regimens for a median duration of 16 months (range: 1-29). Eleven patients (69%) completed treatment, four (25%) died and one (6%) discontinued treatment without relapse. Myelosuppression occurred in 13 (81%) patients a median of 5 weeks (range: 1-11) after starting linezolid, gastrointestinal adverse events occurred in 13 (81%) patients after a median of 8 weeks (range: 1-57) and neurotoxicity occurred in seven (44%) patients after a median of 16 weeks (range: 10-111). Adverse events were managed by combinations of temporary suspension of linezolid, linezolid dose reduction and symptom management. Five (31%) patients required eventual discontinuation of linezolid. Myelosuppression was more responsive to clinical management strategies than was neurotoxicity. Leucopenia and neuropathy occurred more often in males and older age was associated with thrombocytopenia (P < 0.05).


CONCLUSIONS
The majority of MDR TB patients on linezolid had favourable treatment outcomes, although treatment was complicated by adverse events that required extensive clinical management.
Anger
Holly A
HA
New York City Department of Health and Mental Hygiene, Bureau of Tuberculosis Control, 225 Broadway, 22nd floor, New York, NY 10007, USA. hanger@health.nyc.gov
Dworkin
Felicia
F
Sharma
Saarika
S
Munsiff
Sonal S
SS
Nilsen
Diana M
DM
Ahuja
Shama D
SD
D000081:Acetamides / Q000009:adverse effects* / Q000627:therapeutic use*; D000328:Adult; D000368:Aged; D000995:Antitubercular Agents / Q000009:adverse effects* / Q000627:therapeutic use*; D001855:Bone Marrow Diseases / Q000139:chemically induced; D002648:Child; D005260:Female; D005767:Gastrointestinal Diseases / Q000139:chemically induced; D006801:Humans; D015994:Incidence; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D009422:Nervous System Diseases / Q000139:chemically induced; D009519:New York City; D023303:Oxazolidinones / Q000009:adverse effects* / Q000627:therapeutic use*; D012189:Retrospective Studies; D016896:Treatment Outcome; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*; D055815:Young Adult
D000081:Acetamides; D000995:Antitubercular Agents; D023303:Oxazolidinones; D000069349:Linezolid