Abstract
The activity of pyrazinamide (PZA) against eight isolates of Mycobacterium tuberculosis in a murine infection model was evaluated. M. tuberculosis isolates with various degrees of in vitro susceptibility to PZA (MIC range, 32 to > 2,048 micrograms/ml) were used. Four-week-old female mice were infected intravenously with approximately 10(7) viable M. tuberculosis organisms. PZA at 150 mg/kg of body weight was started 1 day postinfection and given 5 days/week for 4 weeks. Infected but untreated mice were compared with PZA-treated mice. Mice were sacrificed at the completion of the treatment period, and viable cell counts were determined from homogenates of spleens and right lungs. PZA had activity in the murine test system against M. tuberculosis isolates for which the MICs were < or = 256 micrograms/ml. However, there was an inconsistent correlation between the absolute MICs and the reductions in organ viable cell counts. Studies with drug-resistant M. tuberculosis isolates with an isogenic background would improve evaluation of drug efficacy in the murine test system. Further evaluation of antimycobacterial agents against monodrug-resistant isolates will provide data that will be useful for development of algorithms for treatment of infection with drug-resistant organisms.
Full Text
The Full Text of this article is available as a PDF (177.1 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Bass J. B., Jr, Farer L. S., Hopewell P. C., O'Brien R., Jacobs R. F., Ruben F., Snider D. E., Jr, Thornton G. Treatment of tuberculosis and tuberculosis infection in adults and children. American Thoracic Society and The Centers for Disease Control and Prevention. Am J Respir Crit Care Med. 1994 May;149(5):1359–1374. doi: 10.1164/ajrccm.149.5.8173779. [DOI] [PubMed] [Google Scholar]
- Butler W. R., Kilburn J. O. Susceptibility of Mycobacterium tuberculosis to pyrazinamide and its relationship to pyrazinamidase activity. Antimicrob Agents Chemother. 1983 Oct;24(4):600–601. doi: 10.1128/aac.24.4.600. [DOI] [PMC free article] [PubMed] [Google Scholar]
- DESSAU F. I., YEAGER R. L., BURGER F. J., WILLIAMS J. H. Pyrazinamide (aldinamide) in experimental tuberculosis of the guinea pig. Am Rev Tuberc. 1952 May;65(5):519–522. [PubMed] [Google Scholar]
- Davidson P. T., Le H. Q. Drug treatment of tuberculosis--1992. Drugs. 1992 May;43(5):651–673. doi: 10.2165/00003495-199243050-00003. [DOI] [PubMed] [Google Scholar]
- Ellard G. A. Absorption, metabolism and excretion of pyrazinamide in man. Tubercle. 1969 Jun;50(2):144–158. doi: 10.1016/0041-3879(69)90020-8. [DOI] [PubMed] [Google Scholar]
- Fischl M. A., Daikos G. L., Uttamchandani R. B., Poblete R. B., Moreno J. N., Reyes R. R., Boota A. M., Thompson L. M., Cleary T. J., Oldham S. A. Clinical presentation and outcome of patients with HIV infection and tuberculosis caused by multiple-drug-resistant bacilli. Ann Intern Med. 1992 Aug 1;117(3):184–190. doi: 10.7326/0003-4819-117-3-184. [DOI] [PubMed] [Google Scholar]
- Grosset J. Present and new drug regimens in chemotherapy and chemoprophylaxis of tuberculosis. Bull Int Union Tuberc Lung Dis. 1990 Jun-Sep;65(2-3):86–91. [PubMed] [Google Scholar]
- Heifets L. B., Flory M. A., Lindholm-Levy P. J. Does pyrazinoic acid as an active moiety of pyrazinamide have specific activity against Mycobacterium tuberculosis? Antimicrob Agents Chemother. 1989 Aug;33(8):1252–1254. doi: 10.1128/aac.33.8.1252. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Klemens S. P., DeStefano M. S., Cynamon M. H. Therapy of multidrug-resistant tuberculosis: lessons from studies with mice. Antimicrob Agents Chemother. 1993 Nov;37(11):2344–2347. doi: 10.1128/aac.37.11.2344. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Konno K., Feldmann F. M., McDermott W. Pyrazinamide susceptibility and amidase activity of tubercle bacilli. Am Rev Respir Dis. 1967 Mar;95(3):461–469. doi: 10.1164/arrd.1967.95.3.461. [DOI] [PubMed] [Google Scholar]
- Lecoeur H. F., Truffot-Pernot C., Grosset J. H. Experimental short-course preventive therapy of tuberculosis with rifampin and pyrazinamide. Am Rev Respir Dis. 1989 Nov;140(5):1189–1193. doi: 10.1164/ajrccm/140.5.1189. [DOI] [PubMed] [Google Scholar]
- MACKANESS G. B. The intracellular activation of pyrazinamide and nicotinamide. Am Rev Tuberc. 1956 Nov;74(5):718–728. doi: 10.1164/artpd.1956.74.5.718. [DOI] [PubMed] [Google Scholar]
- MALONE L., SCHURR A., LINDH H., McKENZIE D., KISER J. S., WILLIAMS J. H. The effect of pyrazinamide (aldinamide) on experimental tuberculosis in mice. Am Rev Tuberc. 1952 May;65(5):511–518. [PubMed] [Google Scholar]
- McClatchy J. K., Tsang A. Y., Cernich M. S. Use of pyrazinamidase activity on Mycobacterium tuberculosis as a rapid method for determination of pyrazinamide susceptibility. Antimicrob Agents Chemother. 1981 Oct;20(4):556–557. doi: 10.1128/aac.20.4.556. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McDERMOTT W., TOMPSETT R. Activation of pyrazinamide and nicotinamide in acidic environments in vitro. Am Rev Tuberc. 1954 Oct;70(4):748–754. doi: 10.1164/art.1954.70.4.748. [DOI] [PubMed] [Google Scholar]
- Pearson M. L., Jereb J. A., Frieden T. R., Crawford J. T., Davis B. J., Dooley S. W., Jarvis W. R. Nosocomial transmission of multidrug-resistant Mycobacterium tuberculosis. A risk to patients and health care workers. Ann Intern Med. 1992 Aug 1;117(3):191–196. doi: 10.7326/0003-4819-117-3-191. [DOI] [PubMed] [Google Scholar]
- YEAGER R. L., MUNROE W. G. C., DESSAU F. I. Pyrazinamide (aldinamide) in the treatment of pulmonary tuberculosis. Am Rev Tuberc. 1952 May;65(5):523–546. [PubMed] [Google Scholar]