title: Whole blood bactericidal activity during treatment of pulmonary tuberculosis.
abstract: 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 log(10) 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 log(10) 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.
authors.affiliation: Department of Medicine, University of Medicine and Dentistry of New Jersey-New Jersey Medical School, Newark, NJ 07103, USA. r.wallis@umdnj.edu
authors.forename: Robert S
authors.initials: RS
authors.lastname: Wallis
authors.forename: Solange A
authors.initials: SA
authors.lastname: Vinhas
authors.forename: John L
authors.initials: JL
authors.lastname: Johnson
authors.forename: Fabíola C
authors.initials: FC
authors.lastname: Ribeiro
authors.forename: Moisés
authors.initials: M
authors.lastname: Palaci
authors.forename: Renata L
authors.initials: RL
authors.lastname: Peres
authors.forename: Ricardo T
authors.initials: RT
authors.lastname: Sá
authors.forename: Reynaldo
authors.initials: R
authors.lastname: Dietze
authors.forename: Allan
authors.initials: A
authors.lastname: Chiunda
authors.forename: Kathleen
authors.initials: K
authors.lastname: Eisenach
authors.forename: Jerrold J
authors.initials: JJ
authors.lastname: Ellner
mesh_terms: D000293:Adolescent; D000328:Adult; D000995:Antitubercular Agents / Q000008:administration & dosage / Q000097:blood / Q000627:therapeutic use*; D019540:Area Under Curve; D001770:Blood Bactericidal Activity / Q000276:immunology*; D004353:Drug Evaluation, Preclinical; D005260:Female; D006801:Humans; D008297:Male; D008826:Microbial Sensitivity Tests; D008875:Middle Aged; D009169:Mycobacterium tuberculosis / Q000187:drug effects* / Q000276:immunology*; D012008:Recurrence; D013183:Sputum / Q000382:microbiology; D014397:Tuberculosis, Pulmonary / Q000097:blood / Q000188:drug therapy* / Q000276:immunology* / Q000382:microbiology
chemical_list: D000995:Antitubercular Agents