Previously licensed anti-mycobacterial drugs: a re-appraisal.


Sirwan Muhsin Muhammed Ameen

School of Science-Sulaimani University, Sulaimaniyah-Iraq


Abstract

The discovery of antimycobacterial agent was the outcome of intensive efforts made between 1930
and 1970 to identify antimicrobial drugs. Sulfonamides (1930s), Streptomycin (1944) and Rifampicin
(1965) are first and the last of the anti-mycobacterial drugs currently in use. Despite the availability
of effective anti-tuberculosis chemotherapy, significant morbidity and mortality due to this disease
continue to occur. The emergence and spread of multi-drug resistant (MDR) and extensively-drug
resistant (XDR) strains of Mycobacterium tuberculosis has more complicated the problem of
tuberculosis (TB) control and reduced the effectiveness of the current anti-TB drug. The present
situation clearly demonstrates the need for a re-evaluation of our knowledge to treating TB and the
current TB drugs. One of the highest achievements of modern medicine has been the development of
antibiotics for the treatment of lethal infections. Unfortunately, the progress for new drugs against
tuberculosis has been very inadequate over the past four decades. In the fight against emerging MDR
and XDR resistance we can no longer rely completely on the finding of new antibiotics; we must also
follow rational approaches to the use of older antibiotics such as sulfonamide. This review provides
a concise historical of previously licensed drugs for treatment of tuberculosis and the targets and their
mode of action of these drugs are briefly discussed.

Key Words:
Mycobacterium
tuberculosis, anti-
tuberculosis drugs


References

[1]   Sakula, A. Robert Koch: Centenary of the Discovery of the Tubercle Bacillus, 1882. Thorax. 37: 246-251. (1983).

[2]   Sakula, A.  Robert Koch: The story of his discoveries in tuberculosis. Ir.J.med. Sci.153; Supp.3-9. (1985).

[3]   Hemmati, M., Seghatoleslam, A.,  Rasti, M. et al. Expression and Purification of Recombinant Mycobacterium tuberculosis (TB) Antigens, ESAT-6, CFP-10 and ESAT-6/CFP-10 and Their Diagnosis Potential for Detection of TB Patients. Iran Red Crescent Med J.13:556-563. (2011).

[4]   Venturini ETurkova AChiappini E et al. Tuberculosis and HIV co-infection in children. BMC Infect Dis. 14 Suppl 1:S5. (2014).

[5]   World Health Organization. Global tuberculosis report: www.who.int/tb/publications/global-report/en/.(2014)

[6]   Migliori, G.B., Dheda, K., Centis, R. et al. Review of multidrug-resistant and extensively drug-resistant TB: global perspectives with a focus on sub-Saharan Africa. Tropical Medicine and International Health.15 (9): 1052-1066. (2010).

[7]   World Health Organization. Extensively drug-resistant tuberculosis (XDR-TB): recommendations for prevention and control. Weekly Epidemiol. Rec., 81, 430–432. (2006).

[8]   Lange, C., Yew, W.W., Migliori, G.B., Raviglione, M. The European Respiratory Journal targets tuberculosis. Eur Respir J. 36: 714-715. (2010).

[9]   Ashburn T and Thor KB. Drug repositioning: identifying and developing new uses for existing. Nat. Rev. Drug Discov. 3, 673–683. (2004).

[10]           Forgacs, P., Wengenack , N. L., Hall, L., Zimmerman , S. K., Silverman, M. L., and Roberts , G. D. Tuberculosis and trimethoprim-sulfamethoxazole. Antimicrob. Agents Chemother. 53:4789-4793. (2009).

[11]           Markowitz, N. Quinn, E.L and Saravolatz, L.D. Trimethoprim­sulfamethoxazole compared with vancomycin for the treatment of Staphylococcus aureus infection. Ann Intern Med.117:390­8. (1992).

[12]           Stein, A. and Raoult, D. Colistin: an antimicrobial for the 21st century? Clin Infect Dis .35:901-902. (2002).

[13]            Crofton, J and Mitchison, D. Streptomycin resistance in pulmonary tuberculosis. Br. Med.J. 2: 1009-1015. (1948).

[14]           Johnson, R., Streicher, E. M., Louw, G.E. et al. Drug Resistance in Mycobacterium tuberculosis. Curr. Issues Mol. Biol. 8: 97-112. (2009).

[15]           Campbell, C.W. History of the Discovery of Sulfaquinoxaline as a Coccidiostat. J. Parasitol., 94: 934–945. (2008).

[16]           Burkhart, C.G and Burkhart, C.N. Overview of Sulfonamides and Related Medications: Query if Mesalamine should be preferred over Dapsone and Sulfasalazine. The Open Dermatology Journal. 3: 65-67. (2009).

[17]           Balganesh T.S, Balasubramanian V and Anand Kumar S. For Tuberculosis: Bottlenecks and path forward. Current Science. 86: 167-176. (2004)

[18]           Chopra, I and Brennan, P. Molecular action of antimycobacterial agents. Tubercle Lung Dis. 78: 89-98. (1998).

[19]           Buttle, G.A.H. The action of sulphanilamide and its derivatives with special reference to tropical diseases. Transactions of the Royal Society of Tropical Medicine and Hygiene. 33: 141-159. (1939).

[20]           George, E and Shambaugh, JR.MD. History of Sulfonamides.Arch Otolaryngol.83:1-2. (1966).

[21]           Amundsen L H. Sulfanilamide and Related Chemotherapeutic Agents. Journal of Chemical Education. 19: 167-171. (1942).

[22]           Spies, H. W., Lepper, M. H., Blatt, N. H. and Dowling, H. F. Tuberculous meningitis treatment with streptomycin, para-aminosalicylic acid and promizole, isoniazid and streptomycin, and isoniazid. Am. Rev. Tuberc. 69:192-204. (1954).

[23]           Behera, D. Tuberculosis. QUARTERLY MEDICAL REVIEW. RAPTAKOS, BRETT & CO. LTD., WORLI MUMBAI 400 030. 61 :( 4). (2010).

[24]           Hinshaw, H.C and McDermott, W. Thiosemicarbazone therapy of tuberculosis in human. Am. Rev. Tuberc. 61:145- 57. (1950).

[25]           Karl H and Pfuetze. Present Status of Chemotherapy in Tuberculosis from the Clinical Standpoint. Chest.11: 220-226. (1945).

[26]           Ellman, P. Investigation in the value of sulfapyridine in the treatment of pulmonary tuberculosis.     Tubercle. 22:296-302. (1941).

[27]           Domagk, G. Ein Beitrag zur Chemotherapie der bakteriellen Infektionen, Deutsche med. Wlchutschr. 61:250. (1935).

[28]           Anderson T. Chemotherapy of pulmonary tuberculosis with sulphetrone. Lancet. 2:135-9. (1948).

[29]           Madigan, D. G., Swift, P. N., Brownlee, G., Payling Wright, G. Treatment of tuberculosis with streptomycin and sulphetrone. Lancet, 2: 897-904. (1947).

[30]           Chang WJ and Goetz MB.). Response to treatment of infection due to Mycobacterium avium complex with trimethoprim-sulfamethoxazole. Clin Infect Dis 14:1267-1268. (1992).

[31]           Clinical and Laboratory Standards Institute. Susceptibility testing of mycobacteria, nocardiae, and other aerobic actinomycetes; Approved Standard. Wayne, PA: CLSI, Document No. M24-A. (2003).

[32]           Ong, W, Sievers A and Leslie DE. Mycobacterium tuberculosis and sulfamethoxazole susceptibility. Antimicrob. Agents Chemother.54: 2748–2749. (2010).

[33]           Huang TS, Kunin CM, Yan BS, et al. Susceptibility of Mycobacterium tuberculosis to sulfamethoxazole, trimethoprim and their combination over a 12 year period in Taiwan. J Antimicrob Chemother; 67: 633-7. (2012).

[34]           Waksman, S. A. Streptomycin: background, isolation, properties, and utilization. Science 118:259–266. (1953).

[35]           Mcdermott, W. Streptomycin in the Treatment of Tuberculosist. J Natl Med Assoc. 41:167-70. (1949).

[36]           Pfuetze KH and Ashe WM. Present Status of Streptomycin In Tuberculosis. chest.41: 446-455. (1948).

[37]           Comroe JH Jr. Pay dirt: the story of streptomycin. Part I. From Waksman to Waksman.117:773-81. (1978).

[38]           Camille G.W. The Practice of Medicinal Chemistry. 3th Edition. Academic Press is an imprint of Elsevier: 20. (2008).

[39]           Schatz AB, Bugie E and Waksman S. Streptomycin, a substance exhibiting antibiotic activity against gram-positive and gram-negative bacteria. Proc. Soc. Exp.Biol. Med. 55:66–69. (1944).

[40]           Hinshaw HC and Feldman WH. Streptomycin in the treatment of clinical and experimental tuberculosis. Ann.N.Y. Acad. Sci.46:175-182. (1946).

[41]           Dickinson. EFFECT OF STREPTOMYCIN ON EXPERIMENTAL TUBERCULOSIS IN GUINEA-PIGS. Brit. J. Pharmacol. 2, 23. (1947).

[42]           Hinshaw HC. , Feldman WH. and Pfuetze, K. H. Treatment  of  tuberculosis  with  streptomycin;  a  summary  of  observations  on  one  hundred. J. Amer. med.Ass.132: 778-782. (1946).

[43]           Imam F., Anwer M.K., Iqbal M. et al. Tuberculosis: Brief Overview and its Shifting Paradigm for Management in India. Int. J. Pharmacol. 6: 755-783. (2010)

[44]           Zhang Y. The Magic Bullets and Tuberculosis Drug Targets. Annu. Rev. Pharmacol. Toxicol.42: 529-64. (2005).

[45]           Daniels M and Hill AB. Chemotherapy for pulmonary tuberculosis in young adults: an analysis of the combined results of three Medical Reserearch Council trials. Brit Med J.1:1162-1168. (1952).

[46]           Jassal M and Bishai W R. Extensively drug-resistant tuberculosis. Lancet Infect Dis.9:19-30. (2009).

[47]           Blanchard J S. Molecular mechanisms of drug resistance in Mycobacterium tuberculosis. Annu Rev Biochem.65: 215-239. (1996).

[48]           De Souza, M.V.N. Promising candidates in clinical trials against multidrug-resistant tuberculosis (MDR-TB) based on natural products. Fitoterapia 80, 453-460. (2009)

[49]           Sensi, P. History of the development of rifampin. Rev. Infect. Dis. 3, 402–406. (1983).

[50]           Saltini, C. (2006).Chemotherapy and diagnosis of tuberculosis. Resp Med.100:2085-2097.

[51]           Davidson PT, Goble M and Lester W. The antituberculosis efficiency of rifampicin in 136 patients. Chest.61:574-578. (1972).

[52]           Vall-Spinosa A. and Lester T.W. Rifampin: Characteristics and role in the chemotherapy of tuberculosis. Ann Intern Med.74:758-760. (1971).

[53]           Kirst H A and Sides G D. New directions for macrolide antibiotics: structural modifications and in vitro activity. Antirnicrob Agents. 33: 1413-1418. (1989).

[54]           Tripathi R. P., Tewari, N., Dwivedi, N. and Tiwari, V. K. Fighting tuberculosis: an old disease with new challenges. Med. Res. Rev. 25:93-131. (2005).

[55]           Kumazawa J and Yagisawa M. The history of antibiotics: the Japanese story. J Infect Chemother. 8:125-133. (2002).

[56]           Sood SK. Macrolides: clarithromycin and azithromycin. Semin Pedatr Infect Dis. 10:23-30. (1999).

[57]           McKenna S, Evans GA and Canadian Infectious Disease Society Antimicrobial Agents Committee. Macrolides: A Canadian Infectious Disease Society Position Paper. Can J Infect Dis.12:218-231. (2001).

[58]           Franzblau, S. G. Drug susceptibility testing of Mycobacterium leprae in the BACTEC 460 system. Antimicrob. Agents Chemother. 33:2115-2117. (1989).

[59]           Franzblau, S. G., and Hastings R. C. In vitro and in vivo activities of macrolides against Mycobacterium leprae. Antimicrob. Agents Chemother. 32:1758-1762. (1988).

[60]           Chan GP, Garcia-Ignacio BY, Chavez VE, et al.Clinical trial of clarithromycin for lepromatous leprosy. Antimicrob Agents Chemother.38:515-517. (1994).

[61]           Grosset JH. Newer drugs in leprosy. Int J Lepr Other Mycobact Dis.69: S14-S18. (2001).

[62]           Truffot-Pernot C, Lounis N, Grosset JH, and Ji B. Clarithromycin is inactive against Mycobacterium tuberculosis. Antimicrob Agents Chemother.39:2827-2828. (1995).

[63]           Rastogi N, Goh KS, Berchel M and Bryskier A In vitro activities of the ketolides telithromycin (HMR 3647) and HMR 3004 compared to those of clarithromycin against slowly growing mycobacteria at pHs 6.8 and 7.4. Antimicrob Agents Chemother. 44:2848-2852. (2000).

[64]           Stoffels K, Traore H, Vanderbist F et al. The effect of combined tobramycin-clarithromycin on Mycobacterium tuberculosis isolates. Int J Tuberc Lung Dis .13: 1041-1044. (2009).

[65]           Bhusal Y, Shiohira CM and Yamane N. Determination of in vitro synergy when three antimicrobial agents are combined against Mycobacterium tuberculosis. Int J Antimicrob Agents. 26: 292-297. (2005).

[66]           Sharma P.C., Jain A and Jain S. Fluoroquinolone Antibacterial: A Review on Chemistry, Microbiology and Therapeutic Prospects. Acta Pol. Pharm.Drug Res.66:587-604. (2009).

[67]           Appelbaum PC and Hunter PA. The fluoroquinolone antibacterials: past, present and future perspectives. Int J Antimicrob Agents.16:5-15. (2000).

[68]           Bartlett J. G., Dowell S. F., Mandell L. A. et al. Practice guidelines for the management of community-acquired pneumonia in adults. Infectious Diseases Society of America. Clin Infect Dis. 31: 347-382. (2000).

[69]           Ginsburg, A.S., Grosset, J.H., and Bishai, W.R. Fluoroquinolones, tuberculosis, and resistance. Lancet Infect. Dis. 3:432-442. (2003).

[70]           Gay, J. D., DeYoung D. R and Roberts G. D. In vitro activities of norfloxacin and ciprofloxacin against Mycobacterium tuberculosis, M. avium complex, M. chelonei, M. fortuitum, and M. kansasii. Antimicrob. Agents Chemother.26:94-96. (1984).

[71]           Watt B. In-vitro sensitivities and treatment of less common mycobacteda. J Antimicrob Chemother.39:567-574. (1997).

[72]           Iseman MD. Tuberculosis therapy: (past), present and future. Eur Respir J. 36: S87-94. (2002).

[73]           Blumberg HM, Burman WJ, Chaisson RE, et al. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: Treatment of Tuberculosis. Am. J. Respir. Crit. Care Med.167: 603-622. (2003).

[74]           World Health Organization. Stop TB Dept. Guidelines for the programmatic management of drug-resistant tuberculosis [WHO/HTM/TB/2006.361]. Geneva: World Health Organization,:38-53. (2006).

[75]           Yew WW, Chan CK, Leung CC, Chau CH, Tam CM, Wong PC, et al. Comparative roles of levofloxacin and ofloxacin in the treatment of multidrug-resistant tuberculosis: preliminary results of a retrospective study from Hong Kong. Chest. 124:1476-81. (2003).

[76]           Tuberculosis Research Centre (Indian Council of Medical Research). Shortening short course chemotherapy: a randomized clinical trial for treatment of smear positive pulmonary tuberculosis with regimens using ofloxacin in the intensive phase. Indian Journal of Tuberculosis. 49:27-38. (2002).

[77]           Nueremberger E L, Yoshimatsu T, Tiagy S et al. Moxifloxacin containing regimen greatly reduces time to cultureconversion in murine tuberculosis. Am J Respir Crit Care Med.169:334-335. (2004).

[78]           Lubasch A, Erbes R, Mauch H and Lode H. Sparfloxacin in the treatment of drug resistant tuberculosis or intolerance of first line therapy. Eur Respir J.17: 641-646. (2001).

[79]           Alvirez- Freites EJ, Carter JL and Cynamon MH. In vitro and in vivo activities of gatifloxacin against Mycobacterium tuberculosis. Antimicrob Agents Chemother.46:1022-1025. (2002).

[80]           Harned RL and Haute T. Recovery of cycloserine.Ind. assignor to commercial solvent corporation , New York, N.Y., a corporation with Maryland.3,124,590. (1964).

[81]           Somaraju V. Drugs used in tuberculosis and leprosy. In Modern Pharmacology with Clinical Applications (6th edn), Craig CR, Stitzel RE (eds). Lippincott Williams & Wilkins: Philadelphia. 557-566. (2003).

[82]           Murdoch JM. Cycloserine in Treatment of Infection of Urinary Tract. Br Med J.21:1055-1058. (1959).

[83]           Achilladelis, B."The Dynamics of Technological Innovation: The Sector of Antibacterial Medicines". Research Policy. 22: 279-308. (1993).

[84]           David, S. Synergic activity of D-cycloserine and β-chloro-D-alanine against Mycobacterium tuberculosis. J. Antimicrob. Chemother. 47: 203-206. (2001).

[85]           Arbex M.A, Varella M.C, Siqueira H.R and Mello F.A. Antituberculosis drugs: drug interactions, adverse effects, and use in special situations. Part 1: first-line drugs. J Bras Pneumol. 36:626-40. (2010).

[86]           Rieder HL. Interventions for Tuberculosis Control and Elimination. © International Union Against Tuberculosis and Lung Disease. 68 boulevard Saint Michel, 75006 Paris, France.41-45. (2002).

[87]           Mario CR.Tuberculosis: The essentials :( Lung biology in health and disease).237:4th Ed. (2010).

[88]           Canetti G, Fox W, Khomenko et al. Advances in techniques of testing  mycobacterial drug sensitivity, and the use of sensitivity testing in tuberculosis control programs. Bull World Health Organ. 41:21-43. (1969).

[89]           World Health Organization. Treatment of Tuberculosis Guidelines. 4th ED. (2010).

[90]           Rastogi N, Labrousse V and Goh KS. In vitro activities of fourteen antimicrobial agents against drug susceptible and resistant clinical isolates of Mycobacterium tuberculosis and comparative intracellular activities against the virulent H37Rv strain in human macrophages. Curr Microbiol .33:167-175. (1996).

[91]           Cohen AC. Pyridoxine in prevention and treatment of convulsions and neurotoxicity due to cycloserine. Ann NY Acad Sci .166:346-349. (1969).

[92]           Salem, I.I., Steffan, G. and Düzgünes, N. Efficacy of clofazimine-modified cyclodextrin against Mycobacterium avium complex in human macrophages. International Journal of Pharmaceutics 260:105-114. (2003). 

[93]           Ausina, V., Condom, M. J., Mirelis, B., Luquin, M., Coll, P and Prats, G. In Vitro Activity of Clofazimine against Rapidly Growing Nonchromogenic Mycobacteria. Antimicrob. Agents Chemother.29: 951-952. .(1986)

[94]           Barry, V.C., Belton, J.G., Conalty, M.L., et al. A new series of phenazines (riminocompounds) with high antituberculosis activity. Nature (London).179:1013-101. (1957).

[95]           Van Landingham, R.M., Walker,L.L.,O Sullivan, J.F. and Shinnivk. Activity of Phenazine Analogs Against Mycobacterium leprae Infections in mice. International Journal of Leprosy.61:406-414. (1993).

[96]           Cholo, M.C., Steel, H.C., Fourie, P. B., Germishuizen, W.A and Anderson, R. Clofazimine: current status and future prospects. J Antimicrob Chemother. 67: 290-298. (2012). 

[97]           Currey, H.L.F. and fowler, P.D. A study of clofazimine in the rat. Br. J. Pharmac. 45: 676-681. (1972).

[98]           Reddy,V.M., Sullivan, J.F. and Gngadharam, P.R.J. Antimycobacterial activities of riminophenazines. J Antimicrob Chemother.43:615-623. (1999).

[99]           Mitnick CD, Shin SS, Seung KJ, et al. Comprehensive treatment of extensively drug-resistant tuberculosis. N Engl J Med .359:563-574. (2008).

[100]       Xu, H.B., Jiang, R.H. and Xiao, H.P. Clofazimine in the treatment of multidrug-resistant tuberculosis.  Clinical Microbiology and Infection. 18:1104-10. (2012).

[101]       Field, S.K. and Cowie, R.L. Treatment of Mycobacterium intracellulare complex lung disease with a Macrolide, Ethambutol and Clofazimine. Chest: 124:1482-1486. (2003).

[102]       Long, R., Nobert, E., Chomy, S. et al. Transcontinental Spread of Multidrug-resistant Mycobacterium bovis. Am J Respir Crit Care Med. 159: 2014–2017. (1999).

[103]       Browne, S.G and Hogerzeil, L.M. “B 663” in the treatment of leprosy. reliminary           report of a pilot trial. Lepr. Rev. 33: 6-10. (1962).

[104]       World Health Organization Study Group on Leprosy, Chemotherapy of leprosy control programs (WHO teehnieal report series 675). Geneva, World Heallh Organization, (1982).

[105]       Caminero JA, Sotgiu G, ZumLa A et al. Best drug treatment for multidrug-resistant and extensively drug-resistant tuberculosis. Lancet Infect Dis. 10: 621-9. (2010).

[106]       Fortun J, Martin-Davila P, Navas E. et al. Linezolid for the treatment of multidrug-resistant tuberculosis. J Antimicrob Chemother. 56:180-185. (2005).

[107]       Piersimoni, C, Tortoli E, Mascellino, M. T. et al. Activity of seven antimicrobial agents, alone and in combination, against AIDS-associated isolates of Mycobacterium avium complex. J Antimicrob Chemother. 36: 497-502. (1995).

[108]       Cohn, D.L., Fisher, E.J., Peng, G.T. et al. A Prospective Randomized Trial of Four Three-Drug Regimens in the Treatment of Disseminated Mycobacterium avium Complex Disease in AIDS Patients: Excess Mortality Associated with High-Dose Clarithromycin. Clinical Infectious Diseases .29:125-133. (1999).

[109]       Lopez de Compadre R. L., Pearlstein R. A., Hopnger A. J  and Seydel J. K.  A quantitative structure-activity relationship analysis of some 4-aminodiphenyl sulfone antibacterial agents using linear free energy and molecular modeling methods. J. Med. Chem. 30:900–906. (1987).

[110]       Legendre DP, Pharm D, Muzny CA M.D and Swiatlo E.M.D., Ph.D. Hansen’s Disease (Leprosy): Current and Future Pharmacotherapy and Treatment of Disease-Related Immunologic Reactions. Pharmacotherapy .32:27-37. (2012).

[111]       Barr J. A short history of Dapsone, or an alternative model of drug  development. J Hist Med Allied Sci. 66: 425-467. (2011).

[112]       Sire DJ and Johnson BL:  Benign familial chronic pemphigus treated with dapsone. Arch Dermatol . 103:262-265. (1971) 

[113]       Buttle G, Stephenson D, Smith S, et al. The treatment of streptococcal infections in mice with 4:4 diaminodiphenylsulfone. Lancet. 1:1331-1334. (1937).

[114]       Shepard C. Leprosy today. N Engl J Med .307:1640-1641. (1982).

[115]       Ooi WW and Moschclla SL. Update on leprosy in immigrants in the United States: Status in the year 2000. Clin Infect Dis .32:930-937. (2001).

[116]       World Health Organization. WHO Expert Committee on Leprosy. Seventh report. World Health Organ Tech Rep Ser. 874:1-43. (1998).

[117]       Pettit JHS and Rees RJW. Sulphone resistance in leprosy: An experimental and clinical study. Lancet.2:673-674. (1964).

[118]       Herbert Fox H. A Critique on Literature of Antituberculous Compounds. Advances in Chemistry.16:28-31. (1956).

[119]       Rastogi N, Goh KS and Labrousse V.  Activity of subinhibitory concentrations of dapsone alone and in combination with cell-wall inhibitors against Mycobacterium avium complex organisms. Eur J Clin Microbiol Infect Dis.12:954-958. (1993).

[120]       Williams D. L., Pittman T. L., Gillis T. P. et al. Simultaneous detection of Mycobacterium leprae and its susceptibility to dapsone using DNA heteroduplex analysis. J. Clin. Microbiol.39:2083-2088. (2001).

[121]       George J and Balakrishnan S. Blood dapsone levels in leprosy patients treated with acedapsone. Indian J Lepr. 58:401-406. (1986).

[122]       Wilkinson, R. G., R. G., Shepherd, J. P., Thomas and Baughn C. Stereospecificity in a new type of synthetic antituberculous agent. J. Am. Chem. Soc. 83: 2212-2213. (1961).

[123]       Schmidt, L. H. Studies of the antituberculosis activity of ethambutol in monkeys. Ann. N.Y. Acad. Sci. 135:747-758. (1966).

[124]       Kemper CA, Havlir D, Haghighat D, et al. The individual microbiologic effect of three antimycobacterial agents, clofazimine, ethambutol, and rifampin, on Mycobacterium avium complex bacteremia in patients with AIDS. J Infect Dis .170:157–64. (1994).

[125]       Wallace RJ, Glassroth, J, Griffith, DE et al. American Thoracic Society. Diagnosis and treatment of disease caused by nontuberculous mycobacteria. Am. J. Respir. Crit. Care Med. 156: S1–S25. (1997).

[126]       Riska PF, Jacobs WR Jr and Alland D. Molecular determinant of drug resistance in tuberculosis. Int J Tuberc Lung Dis. 4: S4-S10. (2000).

[127]       Cheepsattayakorn A and Cheepsattayakorn R. Prospects for new drugs and regimens in the treatment of tuberculosis. J R Coll Physicians Edinb. 38:207–311. (2008).

[128]       Liss RH. Bactericidal activity of ethambutol against. extracellular Mycobacterium tuberculosisand bacilli phagocytized by humanulveolal' macrophages. SA Medical Journal. LXII:15-19. (1982).

[129]       Hershfield E. Tuberculosis: 9. Treatment. CMAJ.161:405-411. (1999).

[130]       Kaur D and Khuller G. In vitro, ex-vivo and in vivo activities of ethambutol and sparfloxacin alone and in combination against mycobacteria. Int J Antimicrob Agents. 17: 51- 55. (2001).

[131]       Place V.A., Peets E.A., Buyske D. A. and Little R.R. Metabolic and special studies of ethambutol in normal volunteers and tuberculous patients. Ann. N.Y. Acad. Sci. 135:775-795. (1966).

[132]       Plinke C, Walter K, Aly S, Ehlers S and Niemann S. Mycobacterium tuberculosis embB Codon 306 Mutations Confer Moderately Increased Resistance to Ethambutol In Vitro and In Vivo. Antimicrob. Agents Chemother. 55: 2891-2896. (2011).

[133]       Slayden RA and Barry CE, III. The genetics and biochemistry of isoniazid resistance in Mycobacterium tuberculosis. Microbes infect. 2:659-669. (2000).

[134]       Meyer H and Mally J. Über Hydrazinderivate der Pyridincarbonsäuren. Monatshefte für Chemie und verwandte Teile anderer Wissenschaften. 23: 393-414. (1912).

[135]       Fox, H. H. The chemical approach to the control of tuberculosis. Science.116:129–134. (1952).

[136]       Selikoff, I. J. and Robitzek, E. H. Tııberculosis Chemotherapy with Hydrazine Derivatives of Isonicotinic Acid: DiS. of Chest, 21: 385-438. (1952).

[137]       International Union Against Tuberculosis Committee on Prophylaxis. Efficacy of various durations of isoniazid preventive therapy for tuberculosis: five years of follow-up in the IUAT trial. Bull World Health Organ. 60: 555-564. (1982).

[138]       Smieja MJ, Marchetti CA, Cook DJ and Smaill FM. Isoniazid for preventing tuberculosis in non-HIV infected persons. Cochrane Database Syst Rev: CD001363. (2000)

[139]       Woldehanna S and Volmink J. Treatment of latent tuberculosis infection in HIV infected persons. Cochrane Database Syst Rev.1: CD000171. (2004).

[140]       Zhang Y, Heym B, Allen B, Young D and Cole ST. The catalase peroxidase gene and isoniazid resistance of Mycobacterium tuberculosis. Nature. 358:591–593. (1992).

[141]       Kergueris MF, Bourin M and Larousse C. Pharmacokinetics of isoniazid: influence of age. Eur J Clin Pharmacol. 30: 335-40. (1986).

[142]       Peloquin CA, Namdar R, Dodge AA and Nix DE. Pharmacokinetics of isoniazid under fasting conditions, with food, and with antacids. Int J Tuberc Lung Dis.3: 703-10. (1999).

[143]       Selikoff I. J., Robitzek E.H., and Ornstein G.G. Treatment of Pulmonary Tuberculosis with Hydrazide Derivatives of Isonicotinic Acid. J. A. M. A. 150:973-980. (1952).

[144]       Mitchison, D. A. Basic mechanisms of chemotherapy. Chest .76:771-781. (1979).

[145]       Nora de Souza, M.V., Bispo, M.F, Gonçalves R.S.B. and Kaiser C.R. Thiourea Derivatives: A Promising Class Against HIV/TB Co-Infection. In Venketaraman V. (ed), Global View of HIV Infection. InTech, Published.127-162. (2011).

[146]       Lambelin, G. Pharmacology and Toxicology of Isoxyl. Antibiot. Chemother. 16: 84–95. (1970).

[147]       Phetsuksiri B.  Baulard ARCooper AM. et al. Antimycobacterial activities of isoxyl and new derivatives through the inhibition of mycolic acid synthesis. Antimicrob Agents Chemother.43:1042-1051. (1999).

[148]       König, A. Discussion on Isoxyl. Antibiotica et Chemotherapia. 16:187-202. (1970).

[149]       Urbancik, B. Clinical experiences with thiocarlide (isoxyl). Antibiot. Chemother. 16:117-123. (1970).

[150]       Schmid, P. C. H. Clinical experiences in cases of primary tuberculosis with tuberculostaticum isoxyl. Antibiot. Chemother. 16:108–116. (1970).

[151]       Winder, F. G., Collins, P. B. and Whelan, D. Effects of ethionamide and isoxyl on mycolic acid synthesis in Mycobacterium tuberculosis BCG. J. Gen. Microbiol. 66:379–380. (1971).

[152]       Bhowruth, V., Brown, A. K., Reynolds, R. C. et al. Symmetrical and unsymmetrical analogues of isoxyl; active agents against Mycobacterium tuberculosis. Bioorg. Med. Chem. Lett.16: 4743-4747. (2006).

[153]       Lehmann J. p-aminosalicylic acid in the treatment of tuberculosis. Lancet 1:15-16. (1946).

[154]       Bernheim F. The effect of salicylate on the oxygen uptake of the tubercle bacillus. Science.92:204. (1940).

[155]       Erdei, A and Snell W.E. Pulmonary tuberculosis treated with p- aminosalicylic acid. Lancet.1:791. (1948).

[156]       Youmans, G. P.; Raleigh, G. W., and Youmans, A. S. The Tuberculostatic Action of Para-Aminosalicylic Acid. J. Bact. 54:409. (1947).

[157]       Cordice, W. V., Hill, L. M. and Wright, L. T. “Use of pyrazinamide (Aldinamide) in the treatment of tuberculous lymphadenopathy and draining sinuses,” J. Nat. M.A. 45:87-98. (1953)

[158]       Zhang, Y., Wade, M. M., Scorpio, A., Zhang, H. and Sun, Z. Mode of action of pyrazinamide: disruption of Mycobacterium tuberculosis membrane transport and energetics by pyrazinoic acid. J. Antimicrob. Chemother. 52:790–795. (2003).

[159]       Fuursted K. Comparison of growth and susceptibility testing of pyrazinamide in different Bactec media using strains of the M. tuberculosis complex. APMIS. 101:154-159. (1993).

[160]       Yew, W. W., Lange, C. and Leung C. C. Treatment of tuberculosis: update 2010. Eur. Respir. J. 37:441–462. (2011).

[161]       Blomberg B. Spinaci S. Fourie B and Laing R. The rationale for recommending fixed-dose combination tablets for treatment of tuberculosis. Bull World Health Organ.79:61–68. (2001).

[162]       McCune, R. M., R. Tompsett, and W. McDermott. The fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. II. The conversion of tuberculosis infection to the latent state by the administration of pyrazinamide and a companion drug. J. Exp. Med. 104:763-802. (1956).

[163]       McCune, R M., and R Tompsett. Fate of Mycobacterium tuberculosis in mouse tissues as determined by the microbial enumeration technique. I. The persistence of drug-susceptible tubercle bacilli in the tissues despite prolonged antimicrobial therapy. J. Exp. Med. 104:737-762. (1956).

[164]       Ahn C., Oh K.H., Kim K., et al. . Effect of peritoneal dialysis on plasma and peritoneal fluid concentrations of isoniazid, pyrazinamide, and rifampin. Perit Dial Int. 23:362-367. (2003)

[165]       Domagk G, Behnisch R, Mietzsch F and SChmidt H. Ueber eine neue, gegen Tuberkelbazillen in vitro wirksame Verbindungsklasse. Naturwissenschaften.33: 315. (1946).

[166]       Barry, C. E. III, Slayden R. A., Sampson A. E and Lee, R. E. Use of genomics and combinatorial chemistry in the development of new antimycobacterial drugs. Biochem. Pharmacol.59: 221–231. (2000).

[167]       Cavanagh, P and McPherson, K. The Thiacetazone sensitivity of Mycobacterium tuberculosis. J. Med. Microbiol.2:237-242. (1969).

[168]       Heifets, L. B., Lindholm-Levy, P. J and Flory, M. Thiacetazone: in vitro activity against Mycobacterium avium and M. tuberculosis. Tubercle. 71:287–291. (1990).

[169]       Barnett M and Dickinson J M. The response to treatment with thiacetazone of guinea-pigs and mice infected with tubercle bacilli obtained from untreated African patients. Tubercle. 44: 417–30. (1963).

[170]       Barry, V. C., Conalty, M. L and Gaffney, E. E. Amithiozone as an adjuvant to isoniazid therapy. Irish J. med. Sci. 343: 299-303. (1954).

[171]       Elliott A M and Foster S D. Thiacetazone: time to call a halt? Considerations on the use of thiacetazone in African populations with a high prevalence of human immunodeficiency virus infection. Tubercle Lung Dis .77: 27–29. (1996).

[172]       Herr JB, Jr, Haney ME, Pittenger GE and Higgins CE. Isolation and characterization of a new peptide antibiotic. Proc Ind Acad Sci. 69: 134. (1960).

[173]       Heifets L and Lindholm-Levy P.  Comparison of bactericidal activities of streptomycin, amikacin, kanamycin, and capreomycin against Mycobacterium avium and M. tuberculosis. Antimicrob Agents Chemother. 33: 1298-301. (1989).

[174]       Heifets L MIC as a quantitative measurement of susceptibility of M. avium to seven antituberculosis drugs. Antimicrob Agents Chemother. 32:1131-1136. (1988).

[175]       Black H. R., Griffith R. S and Peabody A. M. Absorption, excretion and metabolism of capreomycin in normal and diseased states. Ann N Y Acad Sci 135:974-82. (1966).

[176]       Popplewell AG, Miller JD, Greene ME and Landwehr A. Capreomycin in original treatment cases of pulmonary tuberculosis. Ann N Y Acad Sci .135:989-1005. (1996). 

[177]       Klemens S P,Destefano MS and Cynamon MH. Therapy of multidrug-resistant tuberculosis: lessons from studies with mice. Antimicrob Agents Chemother .37: 2344-2347. (1993).

[178]       McClatchy J. K., Kanes W., Davidson P. T and Moulding T. S. Cross-resistance in M. tuberculosis to kanamycin, capreomycin, and viomycin. Tubercle 58:29–34. (1977).

[179]       Morse W. C., Sproat E. F., Arrington C. W and Hawkins J. A. M. tuberculosis in vitro susceptibility and serum level experiences with capreomycin. Ann. N. Y. Acad. Sci. 135:983–988. (1966).

[180]       Zhang, Y and Mitchison, D. The curious characteristics of pyrazinamide: a review. Int J Tuberc Lung Dis.7(1):6-21. (2003).

[181]       Alahari, A., Alibaud, L., Trivelli, X., et al. Mycolic acid methyltransferase, MmaA4, is necessary for thiacetazone susceptibility in Mycobacterium tuberculosis. Mol. Microbiol. 71, 1263–1277. (2009).

[182]       Arbiser JL and Moschella SL. Clofazimine: a review of its medical uses and mechanisms of action. J Am Acad Dermatol.32:241-247. (1995)

[183]       Scior T, Raddatz G, Figueroa R, Roth HJ, and Bisswanger HA. Molecular modeling study on dapsone and sulfonamides comparing structures and properties with respect to anti-leprosy activity. J Mol Model. 3:332-337. (1997).

[184]       Lowary, TL. d-ARABINOFURANOSIDES FROM MYCOBACTERIA: SYNTHESIS AND CONFORMATION. J. Carbohydr. Chem. 21: 691-722. (2002).

[185]       Chain, E.  B. Chemistry and biochemistry of antibiotics. Ann. Rev. of Biochem.27:167-222. (1958).

[186]       Simplício AL., Clancy JM and Gilmer JF. Prodrugs for Amines. Molecules.13: 519-547. (2008).

[187]       Phetsuksiri, B., Jackson, M., Scherman, H. et al. Unique Mechanism of Action of the Thiourea Drug Isoxyl on Mycobacterium tuberculosis. J. Biol. Chem. 278: 53123–53130. (2003).

[188]       Nomoto S, Teshima T, Wakamiya T and Shiba T. The revised structure of capreomycin. J. Antibiot.30:955-959. (1977).

[189]       Zhang, Y., and Yew, W. W. Mechanisms of drug resistance in Mycobacterium tuberculosis. Int. J. Tuber. Lung Dis. 13:1320–1330. (2009).

[190]       Buriankova, K., Doucet-Populaire, F., Dorson, O. et al. Molecular Basis of Intrinsic Macrolide Resistance in the Mycobacterium tuberculosis Complex. Antimicrob. Agents Chemother. 48: 143–150. (2004).

 

[191]       Korduláková, J., Janin, Y.L., Liav, A. et al. Isoxyl Activation is Required for Bacteriostatic Activity against Mycobacterium tuberculosisAntimicrob. Agents Chemother.51: 3824-3829. (2007).

[192]       Maus CE, Plikaytis BB and Shinnick TM. Molecular analysis of crossresistance to capreomycin, kanamycin, amikacin, and viomycin in Mycobacterium tuberculosis. Antimicrob Agents Chemother. 49:3192–3197. (2005).