A Whole Blood Bactericidal Assay for Tuberculosis

The bactericidal activity of orally administered antituberculosis (anti-TB) drugs was determined in a whole blood culture model of intracellular infection in which microbial killing reflects the combined effects of drug and immune mechanisms. Rifampin (Rif) was the most active compound studied and r...

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Veröffentlicht in:	The Journal of infectious diseases 2001-04, Vol.183 (8), p.1300-1303
Hauptverfasser:	Wallis, Robert S., Palaci, Moisés, Vinhas, Solange, Hise, Amy G., Ribeiro, Fabiola Correa, Landen, Katherine, Cheon, Seon-Hee, Song, Ho-Yeon, Phillips, Manijeh, Dietze, Reynaldo, Ellner, Jerrold J.
Format:	Artikel
Sprache:	eng
Schlagworte:	Anti-Infective Agents - pharmacology Antibacterials Antitubercular Agents - pharmacology Antituberculars Aza Compounds Bacterial diseases Bacteriological methods and techniques used in bacteriology Bacteriology Biological and medical sciences Blood Blood Bactericidal Activity Concise Communications Culture Media Drug design Ethambutol - pharmacology Fluoroquinolones Fundamental and applied biological sciences. Psychology Health care administration Human bacterial diseases Humans Infectious diseases Inoculum Isoniazid - pharmacology Levofloxacin Medical sciences Medication administration Microbial Sensitivity Tests - methods Microbiology Mycobacterium tuberculosis Mycobacterium tuberculosis - drug effects Mycobacterium tuberculosis - isolation & purification Ofloxacin - pharmacology Pulmonary tuberculosis pyrazinamide Pyrazinamide - pharmacology Quinolines Rifampin - pharmacology Sterilization Tuberculosis and atypical mycobacterial infections
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Zusammenfassung:	The bactericidal activity of orally administered antituberculosis (anti-TB) drugs was determined in a whole blood culture model of intracellular infection in which microbial killing reflects the combined effects of drug and immune mechanisms. Rifampin (Rif) was the most active compound studied and reduced the number of viable bacilli by >4 logs. Isoniazid (INH), 2 quinolones, and pyrazinamide (PZA) showed intermediate levels of activity. Ethambutol exerted only a bacteristatic effect; amoxicillin/clavulanate was inactive. The combination of INH-Rif-PZA showed strong activity against 11 drug-sensitive isolates (mean, −3.8 log) but no activity against 12 multidrug-resistant (MDR) strains. The combination of levofloxacin-PZA-ethambutol had intermediate bactericidal activity against MDR isolates (mean, −1.2 log) but failed to equal that of INH-Rif-PZA against sensitive isolates (P
ISSN:	0022-1899 1537-6613
DOI:	10.1086/319679