Linezolid for the treatment of multidrug-resistant tuberculosis.
OBJECTIVE
In vitro studies have shown good activity of linezolid against Mycobacterium tuberculosis, including multidrug-resistant strains. However, clinical experience with linezolid in tuberculosis is scarce.


METHODS
We report our clinical experience with five consecutive patients with multidrug-resistant tuberculosis infection treated with combination regimens that included linezolid.


RESULTS
Two patients had multidrug-resistant Mycobacterium bovis infection, with resistance to 12 antituberculous agents (one of them with HIV co-infection and <50 CD4 cells/mm(3)). The other three patients were infected by multidrug-resistant M. tuberculosis strains, with resistance to all first-line drugs and other second-line drugs. All patients received linezolid in combination with thiacetazone, clofazimine or amoxicillin/clavulanate. Susceptibility tests showed linezolid MIC values < or =0.5 mg/L against all tuberculosis strains tested (standard proportion method, Middlebrook agar 7H10). In all cases, tuberculosis cultures from respiratory samples were sterile after 6 weeks of therapy. Three patients have clinical and microbiological cure of tuberculosis with a combination regimen with linezolid (range: 5-24 months). One patient was lost to follow-up at month 5. The remaining patient has completed 11 months of therapy and is still on treatment. Four patients developed anaemia and needed blood transfusions. In two of these patients, the linezolid daily-dose (600 mg twice a day) was successfully reduced to 50% (300 mg twice a day) to decrease toxicity while maintaining efficacy. Peripheral neuropathy (two patients) and pancreatitis (one patient) were other adverse events observed during linezolid treatment.


CONCLUSIONS
In our experience, linezolid has been a valid alternative drug in the management of multidrug-resistant tuberculosis. The prolonged use of linezolid is frequently associated with toxicity, mainly anaemia and peripheral neuropathy, that requires special management.
Fortún
Jesús
J
Infectious Diseases Department, Ramón y Cajal Hospital, Madrid, Spain. fortun.hrc@salud.madrid.org
Martín-Dávila
Pilar
P
Navas
Enrique
E
Pérez-Elías
Ma Jesús
MJ
Cobo
Javier
J
Tato
Marta
M
De la Pedrosa
Elia Gómez-G
EG
Gómez-Mampaso
Enrique
E
Moreno
Santiago
S
D000081:Acetamides / Q000009:adverse effects / Q000627:therapeutic use*; D000328:Adult; D005260:Female; D006801:Humans; D000069349:Linezolid; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D023303:Oxazolidinones / Q000009:adverse effects / Q000627:therapeutic use*; D018088:Tuberculosis, Multidrug-Resistant / Q000188:drug therapy*
D000081:Acetamides; D023303:Oxazolidinones; D000069349:Linezolid