Whole Blood Bactericidal Activity during Treatment of Pulmonary Tuberculosis

• Published in: The Journal of infectious diseases Vol. 187; no. 2; pp. 270 - 278
• Main Authors: Wallis, Robert S., Vinhas, Solange A., Johnson, John L., Ribeiro, Fabíola C., Palaci, Moisés, Peres, Renata L., Sá, Ricardo T., Dietze, Reynaldo, Chiunda, Allan, Eisenach, Kathleen, Ellner, Jerrold J.
• Format: Journal Article
• Language: English
• Published: Chicago, IL The University of Chicago Press 15.01.2003; University of Chicago Press; Oxford University Press
• Subjects: Adolescent; Adult; Antibacterial agents; Antibiotics. Antiinfectious agents. Antiparasitic agents; Antitubercular Agents - administration & dosage; Antitubercular Agents - blood; Antitubercular Agents - therapeutic use; Antituberculars; Area Under Curve; Bacteria; Biological and medical sciences; Blood; Blood Bactericidal Activity - immunology; Chemotherapy; Dosage; Drug Evaluation, Preclinical; Female; Humans; Male; Medical sciences; Microbial Sensitivity Tests; Middle Aged; Mycobacterium tuberculosis; Mycobacterium tuberculosis - drug effects; Mycobacterium tuberculosis - immunology; Pharmacology. Drug treatments; Pulmonary tuberculosis; Recurrence; Relapse; Sputum; Sputum - microbiology; Sterilization; Tuberculosis; Tuberculosis, Pulmonary - blood; Tuberculosis, Pulmonary - drug therapy; Tuberculosis, Pulmonary - immunology; Tuberculosis, Pulmonary - microbiology; Human; Lung disease; Prognosis; Respiratory disease; Lung; Biological marker; Mycobacterial infection; Immunity; Biological activity; Bactericidal effect; Infection; Whole blood; Chemotherapy; Treatment; Tuberculosis; Bacteriosis; Antituberculous agent
• ISSN: 0022-1899; 1537-6613
• DOI: 10.1086/346053

The timely evaluation of new drugs that can be used to shorten tuberculosis (TB) treatment will require surrogate markers for relapse. This study examined bactericidal activity against intracellular Mycobacterium tuberculosis in whole blood culture (whole blood bactericidal activity; WBA) during TB treatment. In the absence of chemotherapy, immune mechanisms in patient blood resulted in bacteriostasis, whereas administration of oral chemotherapy resulted in bacillary killing. Total WBA per dose was greater during the intensive phase of treatment than during the continuation phase (mean, −2.32 vs. −1.67 log10 cfu-days, respectively; P<.001). Cumulative WBA throughout treatment was greater in subjects whose sputum cultures converted to negative by the eighth week of treatment than in those for whom conversion was delayed (mean, −365 vs. −250 log10 cfu-days; P=.04) and correlated with the rate of decrease of sputum colony-forming unit counts during the first 4 weeks of treatment (P=.018), both of which are indicative of prognosis. These findings indicate that measurement of WBA may have a role in assessing the sterilizing activity of new anti-TB drugs