Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis.
BACKGROUND
Linezolid, the first oxazolidinone approved for clinical use, has effective in vitro and promising in vivo activity against Mycobacterium tuberculosis.


OBJECTIVE
To evaluate the early and extended early bactericidal activity of linezolid in patients with pulmonary tuberculosis.


METHODS
Randomized open label trial. Thirty patients with newly diagnosed smear-positive pulmonary tuberculosis (10 per arm) were assigned to receive isoniazid (300 mg daily) and linezolid (600 mg twice daily or 600 mg once daily) for 7 days. Sputum for quantitative culture was collected for 2 days before and then daily during 7 days of study drug administration. Bactericidal activity was estimated by measuring the decline in bacilli during the first 2 days (early bactericidal activity) and the last 5 days of study drug administration (extended early bactericidal activity).


RESULTS
The mean early bactericidal activity of isoniazid (0.67 log10 cfu/ml/d) was greater than that of linezolid twice and once daily (0.26 and 0.18 log10 cfu/ml/d, respectively). The extended early bactericidal activity of linezolid between Days 2 and 7 was minimal.


CONCLUSIONS
Linezolid has modest early bactericidal activity against rapidly dividing tubercle bacilli in patients with cavitary pulmonary tuberculosis during the first 2 days of administration, but little extended early bactericidal activity. Clinical trial registered with www.clinicaltrials.gov (NCT00396084).
Dietze
Reynaldo
R
Núcleo de Doenças Infecciosas Centro de Ciências da Saúde, Universidade Federal do Espírito Santo, Av. Marechal Campos, 1468 Maruípe,Vitória-ES Brazil, CEP 29040-091. rdietze@ndi.ufes.br
Hadad
David Jamil
DJ
McGee
Bryan
B
Molino
Lucilia Pereira Dutra
LP
Maciel
Ethel Leonor Noia
EL
Peloquin
Charles A
CA
Johnson
Denise F
DF
Debanne
Sara M
SM
Eisenach
Kathleen
K
Boom
W Henry
WH
Palaci
Moises
M
Johnson
John L
JL
D000081:Acetamides / Q000493:pharmacokinetics / Q000627:therapeutic use*; D000328:Adult; D000904:Antibiotics, Antitubercular / Q000493:pharmacokinetics / Q000494:pharmacology*; D015169:Colony Count, Microbial; D004334:Drug Administration Schedule; D004359:Drug Therapy, Combination; D005260:Female; D006801:Humans; D007538:Isoniazid / Q000493:pharmacokinetics / Q000627:therapeutic use; D000069349:Linezolid; D008297:Male; D008875:Middle Aged; D023303:Oxazolidinones / Q000493:pharmacokinetics / Q000627:therapeutic use*; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000382:microbiology; D055815:Young Adult
D000081:Acetamides; D000904:Antibiotics, Antitubercular; D023303:Oxazolidinones; D000069349:Linezolid; D007538:Isoniazid
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