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Drugs
Published in: Drugs 17/2010

01-12-2010 | Leading Article

Drugs in Development for Tuberculosis

Author: Dr Ann M. Ginsberg, MD, PhD

Published in: Drugs | Issue 17/2010

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Abstract

Tuberculosis (TB) drug research and development efforts have resurged in the past 10 years to meet urgent medical needs, but enormous challenges remain. These urgent needs are largely driven by the current long and arduous multidrug regimens, which have significant safety, tolerability and compliance issues; rising and disturbing rates of multidrug- and extensively drug-resistant TB; the existence of approximately 2 billion individuals already latently infected with Mycobacterium tuberculosis, the causative pathogen of TB; and a global TB-HIV co-epidemic. Stakeholders in TB drug development are moving to enable and streamline development and registration of novel, multidrug treatment regimens, comprised of multiple new chemical entities with novel mechanisms of action that do not demonstrate cross-resistance to current first- and second-line TB drugs. Ideally, these new regimens will ultimately provide a short, simple treatment suitable for essentially all TB patients, whether sensitive or resistant to the current anti-TB agents, whether HIV-positive or -negative, and irrespective of patient age.
This article reviews the challenges faced by those trying to develop these novel regimens and the key agents currently in clinical testing for TB; the latter are organized for discussion into three categories: (i) novel drugs (TMC207, SQ109, sudoterb [LL3858]); (ii) present first-line TB drugs being re-evaluated to optimize their efficacy (rifampicin, rifapentine); and (iii) currently licensed drugs for other indications and ‘next-generation’ compounds of the same chemical class being repurposed for TB (gatifloxacin and moxifloxacin; linezolid, PNU100480 and AZD5847; metronidazole, OPC-67683 and PA-824).
Literature
1.
World Health Organization. Global tuberculosis control: a short update to the 2009 report. Geneva: WHO, 2009. Report no.: WHO/HTM/TB/2009.426
2.
World Health Organization. Global tuberculosis control 2009. Geneva: WHO, 2009. Report no.: WHO/HTM/TB/2009.411
3.
Sterling TR, Pham PA, Chaisson RE. HIV infection-related tuberculosis: clinical manifestations and treatment. Clin Infect Dis 2010 May 15; 50 Suppl. 3: S223–300PubMedCrossRef
4.
World Health Organization. Multidrug and extensively drug-resistant TB (M/XDR-TB): 2010 global report on surveillance and response. Geneva: WHO, 2010. Report no.: WHO/HTM/TB/2010.3
5.
Centers for Disease Control and Prevention. Emergence of Mycobacterium tuberculosis with extensive resistance to second-line drugs worldwide, 2000–2004. MMWR Morb Mortal Wkly Rep 2006; 55: 301–5
6.
Fox W, Ellard GA, Mitchison DA. Studies on the treatment of tuberculosis undertaken by the British Medical Research Council Tuberculosis Units 1946–1986, with relevant subsequent publications. Int J Tuberc Lung Dis 1999; 3: S231–79PubMed
7.
van Niekerk C, Ginsberg A. Assessment of global capacity to conduct tuberculosis drug development trials: do we have what it takes? Int J Tuberc Lung Dis 2009; 13: 1367–72PubMed
8.
9.
Andries K, Verhasselt P, Guillemont J, et al. A diarylquinoline drug active on the ATP synthase of Mycobacterium tuberculosis. Science 2005; 307: 223–7PubMedCrossRef
10.
Koul A, Dendouga N, Vergauwen K, et al. Diarylquinolines target subunit c of mycobacterial ATP synthase. Nat Chem Biol 2007; 3: 323–4PubMedCrossRef
11.
Huitric E, Verhasselt P, Andries K, et al. In vitro antimycobacterial spectrum of a diarylquinoline ATP synthase inhibitor. Antimicrob Agents Chemother 2007; 51: 4202–4PubMedCrossRef
12.
Haagsma AC, Abdillahi-Ibrahim R, Wagner MJ, et al. Selectivity of TMC207 towards mycobacterial ATP synthase compared with that towards the eukaryotic homologue. Antimicrob Agents Chemother 2009 Mar; 53(3): 1290–2PubMedCrossRef
13.
Koul A, Vranckx L, Dendouga N, et al. Diarylquinolines are bactericidal for dormant mycobacteria as a result of disturbed ATP homeostasis. J Biol Chem 2008; 283: 25273–80PubMedCrossRef
14.
Ibrahim M, Andries K, Lounis N, et al. Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. Antimicrob Agents Chemother 2007; 51: 1011–5PubMedCrossRef
15.
Lounis N, Veziris N, Chauffour A, et al. Combinations of R207910 with drugs used to treat multidrug-resistant tuberculosis have the potential to shorten treatment duration. Antimicrob Agents Chemother 2006; 50: 3543–7PubMedCrossRef
16.
Rustomjee R, Diacon AH, Allen J, et al. Early bactericidal activity and pharmacokinetics of the diarylquinoline TMC207 in treatment of pulmonary tuberculosis. Antimicrob Agents Chemother 2008; 52: 2831–5PubMedCrossRef
17.
Diacon AH, Pym A, Grobusch M, et al. The diarylquinoline TMC207 for multidrug resistant tuberculosis. N Engl J Med 2009; 360: 2397–405PubMedCrossRef
18.
Diacon AH, Pym A, Grobusch MP, et al. Final results from stage 1 of a double-blind, placebo-controlled trial with TMC207 in patients with multi-drug resistant (MDR) tuberculosis (TB) [abstract no. L1-521a]. Inter-science Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA)
19.
20.
Reddy VM, Einck L, Andries K, et al. In vitro interactions between new antitubercular drug candidates SQ109 and TMC 207. Antimicrob Agents Chemother 2010 Jul; 54(7): 2840–6PubMedCrossRef
21.
22.
Deidda D, Lampis G, Fioravanti R, et al. Bactericidal activities of the pyrrole derivative BM212 against multidrug-resistant and intramacrophagic Mycobacterium tuberculosis strains. Antimicrob Agents Chemother 1998; 2: 3035–7
23.
Arora SK, Sinha N, Sinha RK, et al. Synthesis and in vitro anti-mycobacterial activity of a novel anti-TB composition LL4858 [abstract no. F-1115]. American Society for Microbiology: program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 2004: 212
24.
Sinha RK, Arora SK, Sinha N, et al. In vivo activity of LL4858 against Mycobacterium tuberculosis [abstract no. F-1116]. American Society for Microbiology: program and abstracts of the 44th Interscience Conference on Antimicrobial Agents and Chemotherapy. Washington, DC: American Society for Microbiology, 2004: 212
25.
Protopopova M, Hanrahan C, Nikonenko B, et al. Identification of a new antitubercular drug candidate, SQ109, from a combinatorial library of 1,2-ethylenediamines. J Antimicrob Chemother 2005; 56: 968–74PubMedCrossRef
26.
Boshoff HI, Myers TG, Copp BR, et al. The transcriptional responses of Mycobacterium tuberculosis to inhibitors of metabolism: novel insights into drug mechanisms of action. J Biol Chem 2004; 279: 40174–84PubMedCrossRef
27.
Horwith G, Einck L, Protopopova M, et al. Phase 1 safety and pharmacokinetics of SQ109, a new diamine antituberculosis drug [abstract]. 45th IDSA Annual Meeting; 2007 Oct 4–7; San Diego (CA)
28.
National Institute of Allergy and Infectious Diseases (NIAID). Dose escalation study of SQ109 in healthy adult Volunteers [ClinicalTrials.gov identifier NCT00866190]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
29.
Chen P, Gearhart J, Protopopova M, et al. Synergistic interactions of SQ109, a new ethylene diamine, with frontline antitubercular drugs in vitro. J Antimicrob Chemother 2006; 58: 332–7PubMedCrossRef
30.
Nikonenko BV, Protopopova M, Samala R, et al. Drug therapy of experimental tuberculosis (TB): improved outcome by combining SQ109, a new diamine antibiotic, with existing TB drugs. Antimicrob Agents Chemother 2007; 51: 1563–5PubMedCrossRef
31.
East African/British Medical Research Council. Controlled clinical trial of shortcourse (6-month) regimens of chemotherapy for treatment of pulmonary tuberculosis. Lancet 1972; 1: 1079–85
32.
Jayaram R, Gaonkar S, Kaur P, et al. Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother 2003; 47: 2118–24PubMedCrossRef
33.
Rosenthal IM, Zhang M, Williams KN, et al. Daily dosing of rifapentine cures tuberculosis in three months or less in the murine model. PLoS Med 2007; 4: e344PubMedCrossRef
34.
Diacon AH, Patientia RF, Venter A, et al. Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother 2007; 51: 2994–6PubMedCrossRef
35.
Jindani A, Aber VR, Edwards EA, et al. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis 1980; 121: 939–49PubMed
36.
African Poverty Related Infection Oriented Research Initiative, Kilimanjaro Christian Medical Centre, Tanzania, et al. Pharmacokinetics and pharmacodynamics of high versus standard dose rifampicin in patients with pulmonary tuberculosis (high RIF) [ClinicalTrials.gov identifier NCT00760149]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
37.
Johns Hopkins University, Federal University of Rio de Janeiro. Study of daily rifapentine for pulmonary tuberculosis [ClinicalTrials.gov identifier NCT00814671]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
38.
Centers for Disease Control and Prevention. TBTC study 29: rifapentine during intensive phase tuberculosis (TB) treatment [ClinicalTrials.gov identifier NCT00694629]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
39.
40.
Johns Hopkins University, Federal University of Rio de Janeiro. Rifapentine plus moxifloxacin for treatment of pulmonary tuberculosis (phase 2 study) [ClinicalTrials. gov identifier NCT00728507]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
41.
Centers for Disease Control and Prevention. High dose rifapentine pharmacokinetics, tolerability and safety dosage rifapentine for treatment of tuberculosis (TBTC29PK) [ClinicalTrials.gov identifier NCT01043575]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
42.
Martinez E, Collazos J, Mayo J. Hypersensitivity reactions to rifampin. Pathogenetic mechanisms, clinical manifestations, management strategies, and review of the anaphylactic-like reactions. Medicine (Baltimore) 1999; 78: 361–9
43.
Dooley K, Flexner C, Hackman J, et al. Repeated administration of high-dose intermittent rifapentine reduces rifapentine and moxifloxacin plasma concentrations. Antimicrob Agents Chemother 2008; 52: 4037–42PubMedCrossRef
44.
Rustomjee R, Lienhardt C, Kanyok T, et al., Gatifloxacin for TB (OFLOTUB) study team. A phase II study of the sterilising activities of ofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis 2008 Feb; 12(2): 128–38PubMed
45.
Institut de Recherche pour le Developpement, World Health Organization European Commission. A controlled trial of a 4-month quinolone-containing regimen for the treatment of pulmonary tuberculosis [ClinicalTrials. gov identifier NCT00216385]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
46.
University College, London, Medical Research Council, et al. Controlled comparison of two moxifloxacin containing treatment shortening regimens in pulmonary tuberculosis (REMoxTB) [ClinicalTrials.gov identifier NCT00864383]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
47.
Burman WJ, Goldberg S, Johnson JL, et al. Moxifloxacin versus ethambutol in the first 2 months of treatment for pulmonary tuberculosis. Am J Respir Crit Care Med 2006 Aug 1; 174(3): 331–8PubMedCrossRef
48.
Conde MB, Efron A, Loredo C, et al. Moxifloxacin versus ethambutol in the initial treatment of tuberculosis: a double-blind, randomised, controlled phase II trial. Lancet 2009; 373(9670): 1183–9PubMedCrossRef
49.
Dorman SE, Johnson JL, Goldberg S, et al., Tuberculosis Trials Consortium. Substitution of moxifloxacin for isoniazid during intensive phase treatment of pulmonary tuberculosis. Am J Respir Crit Care Med 2009 Aug 1; 180(3): 273–80PubMedCrossRef
50.
Crumplin GC, Kenwright M, Hirst T. Investigations into the mechanism of action of the antibacterial agent norfloxacin. J Antimicrob Chemother 1984; 13 Suppl. B: 9–23PubMedCrossRef
51.
Drlica K. Biology of bacterial deoxyribonucleic acid topoisomerases. Microbiol Rev 1984; 48: 273–89PubMed
52.
Rodríguez JC, Ruiz M, López M, et al. In vitro activity of moxifloxacin, levofloxacin, gatifloxacin and linezolid against mycobacterium tuberculosis. Int J Antimicrob Agents 2002 Dec; 20(6): 464–7PubMedCrossRef
53.
Alvirez-Freites EJ, Carter JL, Cynamon MH. In vitro and in vivo activities of gatifloxacin against mycobacterium tuberculosis. Antimicrob Agents Chemother 2002; 46: 1022–5PubMedCrossRef
54.
Cynamon M, Sklaney MR. Gatifloxacin and ethionamide as the foundation for therapy of tuberculosis. Antimicrob Agents Chemother 2003; 47: 2442–4PubMedCrossRef
55.
Gillespie SH, Billington O. Activity of moxifloxacin against mycobacteria. J Antimicrob Chemother 1999; 44: 393–5PubMedCrossRef
56.
Hu Y, Coates AR, Mitchison DA. Sterilizing activities of fluoroquinolones against rifampin-tolerant populations of Mycobacterium tuberculosis. Antimicrob Agents Chemother 2003; 47: 653–7PubMedCrossRef
57.
Ji B, Lounis N, Maslo C, et al. In vitro and in vivo activities of moxifloxacin and clinafloxacin against mycobacterium tuberculosis. Antimicrob Agents Chemother 1998; 42: 2066–9PubMed
58.
Johnson JL, Hadad DJ, Boom WH, et al. Early and extended early bactericidal activity of levofloxacin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int J Tuberc Lung Dis 2006 Jun; 10(6): 605–12PubMed
59.
Shandil RK, Jayaram R, Kaur P, et al. Moxifloxacin, ofloxacin, sparfloxacin, and ciprofloxacin against Mycobacterium tuberculosis: evaluation of in vitro and pharmacodynamic indices that best predict in vivo efficacy. Antimicrob Agents Chemother 2007 Feb; 51(2): 576–82PubMedCrossRef
60.
Gatifloxacin and moxifloxacin: two new fluoroquinolones. Med Lett Drugs Ther 2000; 42: 15–7
61.
Lipsky BA, Baker CA. Fluoroquinolone toxicity profiles: a review focusing on newer agents. Clin Infect Dis 1999; 28: 352–64PubMedCrossRef
62.
Park-Wyllie LY, Juurlink DN, Kopp A, et al. Outpatient gatifloxacin therapy and dysglycemia in older adults. N Engl J Med 2006; 354: 1352–61PubMedCrossRef
63.
Gavin III JR, Kubin R, Choudhri S, et al. Moxifloxacin and glucose homeostasis: a pooled-analysis of the evidence from clinical and postmarketing studies. Drug Saf 2004; 27: 671–86PubMedCrossRef
64.
Ball P. Quinolone-induced QT interval prolongation: a not-so-unexpected class effect. J Antimicrob Chemother 2000; 45: 557–9PubMedCrossRef
65.
Rubinstein E, Camm J. Cardiotoxicity of fluoroquinolones. J Antimicrob Chemother 2002 Apr 1; 49(4): 593–6PubMedCrossRef
66.
Hooper DC, Rubinstein 3rd E, editors. Quinolone antimicrobial agents. 3rd ed. Washington, DC: ASM Press, 2003
67.
Weiner M, Burman W, Luo CC, et al. Effects of rifampin and multidrug resistance gene polymorphism on concentrations of moxifloxacin. Antimicrob Agents Chemother 2007; 51(8): 2861–1PubMedCrossRef
68.
Nijland HM, Ruslami R, Suroto AJ, et al. Rifampicin reduces plasma concentrations of moxifloxacin in patients with tuberculosis. Clin Infect Dis 2007 Oct 15; 45(8): 1001–7PubMedCrossRef
69.
Desai CR, Heera S, Patel A, et al. Role of metronidazole in improving response and specific drug sensitivity in advanced pulmonary tuberculosis. J Assoc Physicians India 1989 Nov; 37(11): 694–7PubMed
70.
National Institute of Allergy and Infectious Diseases. Metronidazole for pulmonary tuberculosis (South Korea) [ClinicalTrials.gov identifier: NCT00425113]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Sep 15]
71.
Matsumoto M, Hashizume H, Tomishige T, et al. OPC-67683, a nitro-dihydro-imidazooxazole derivative with promising action against tuberculosis in vitro and in mice. PLoS Med 2006 Nov; 3(11): e466PubMedCrossRef
72.
Manjunatha UH, Boshoff H, Dowd CS, et al. Identification of a nitroimidazo-oxazine-specific protein involved in PA-824 resistance in mycobacterium tuberculosis. Proc Natl Acad Sci U S A 2006 Jan 10; 103(2): 431–6PubMedCrossRef
73.
Singh R, Manjunatha U, Boshoff HI, et al. PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science 2008; 322: 1392–5PubMedCrossRef
74.
Lenaerts AJ, Gruppo V, Marietta KS, et al. Preclinical testing of the nitroimidazopyran PA-824 for activity against mycobacterium tuberculosis in a series of in vitro and in vivo models. Antimicrob Agents Chemother 2005; 49: 2294–301PubMedCrossRef
75.
Stover CK, Warrener P, VanDevanter DR, et al. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 2000; 405: 962–6PubMedCrossRef
76.
Tyagi SE, Nuermberger T, Yoshimatsu K, et al. Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 2005; 49: 2289–93PubMedCrossRef
77.
Nuermberger E, Tyagi S, Tasneen R, et al. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob Agents Chemother 2008 Apr; 52(4): 1522–4PubMedCrossRef
78.
Nuermberger E, Rosenthal I, Tyagi S, et al. Combination chemotherapy with the nitroimidazopyran PA-824 and first-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 2006 Aug; 50(8): 2621–5PubMedCrossRef
79.
Tasneen R, Tyagi S, Williams K, et al. Enhanced bactericidal activity of rifampin and/or pyrazinamide when combined with PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 2008 Oct; 52(10): 3664–8PubMedCrossRef
80.
Ginsberg AM, Laurenzi MW, Rouse DJ, et al. Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects. Antimicrob Agents Chemother 2009; 53: 3720–5PubMedCrossRef
81.
Ginsberg AM, Laurenzi MW, Rouse DJ, et al. Assessment of the effects of the nitroimidazo-oxazine PA-824 on renal function in healthy subjects. Antimicrob Agents Chemother 2009 Sep; 53(9): 3726–33PubMedCrossRef
82.
Diacon AH, Dawson R, Hanekom M, et al. The safety, tolerability and early bactericidal activity and pharmacokinetics of PA824 in previously untreated, uncomplicated, sputum smear-positive pulmonary tuberculosis patients. Antimicrob Agents Chemother 2010 Aug; 54(8): 3402–7PubMedCrossRef
83.
Global Alliance for TB Drug Development. Evaluation of early bactericidal activity in pulmonary tuberculosis [ClinicalTrials.gov identifier NCT00944021]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
84.
Erondu N, Diacon A, Dawson R, et al. PA-824 exhibits dose-dependent bactericidal activity in a 14-day early bactericidal activity (EBA) study, consistent with time over MIC (T>MIC) as the PD driver [abstract no. B-1156a]. Interscience Conference on Antimicrobial Agents and Chemotherapy; 2010 Sep 12–15; Boston (MA)
85.
Otsuka Pharmaceutical Development & Commercialization, Inc. A placebo-controlled, phase 2 trial to evaluate OPC 67683 in patients with pulmonary sputum culture-positive, multidrug-resistant tuberculosis (TB) [ClinicalTrials.gov identifier NCT00685360]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
86.
Otsuka Pharmaceutical Development & Commercialization, Inc. Safety and pharmacokinetics (PK) in multidrug-resistant (MDR) refractive tuberculosis [ClinicalTrials. gov identifier NCT01131351]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
87.
Alcala L, Ruiz-Serrano MJ, Perez-Fernandez Turegano C, et al. In vitro activities of linezolid against clinical isolates of Mycobacterium tuberculosis that are susceptible or resistant to first-line antituberculous drugs. Antimicrob Agents Chemother 2003; 47: 416–7PubMedCrossRef
88.
Cynamon MH, Klemens SP, Sharpe CA, et al. Activities of several novel oxazolidinones against Mycobacterium tuberculosis in a murine model. Antimicrob Agents Chemother 1999; 43: 1189–91PubMed
89.
Vinh DC, Rubinstein E. Linezolid: a review of safety and tolerability. J Infect 2009; 59 Suppl. 1: S59–74PubMedCrossRef
90.
Schecter GF, Scott C, True L, et al. Linezolid in the treatment of multidrug-resistant tuberculosis. Clin Infect Dis 2010; 50: 49–55PubMedCrossRef
91.
Migliori GB, Eker B, Richardson MD, et al., TBNET Study Group. A retrospective TBNET assessment of linezolid safety, tolerability and efficacy in multidrug-resistant tuberculosis. Eur Respir J 2009; 34: 387–93PubMedCrossRef
92.
Dietze R, Hadad DJ, McGee B, et al. Early and extended early bactericidal activity of linezolid in pulmonary tuberculosis. Am J Respir Crit Care Med 2008 Dec 1; 178(11): 1180–5PubMedCrossRef
93.
U.S. National Institutes of Health. A phase 2a, randomized, 2-arm, open-label, clinical trial of the efficacy of linezolid combined with antituberculous therapy in subjects with extensively drug-resistant (XDR) pulmonary tuberculosis [ClinicalTirals.gov identifier NCT00727844]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
94.
Centers for Disease Control and Prevention, University of KwaZulu, et al. TBTC S30: Safety and tolerability of low dose linezolid in MDR TB (LiMiT) [ClinicalTrials.gov identifier NCT00664313]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
95.
Park IN, Hong SB, Oh YM, et al. Efficacy and tolerability of daily half dose linezolid in patients with intractable multidrug-resistant tuberculosis. J Antimicrob Chemother 2006; 58: 701–4PubMedCrossRef
96.
Koh WJ, Kwon OJ, Gwak H, et al. Daily 300 mg dose of linezolid for the treatment of intractable multidrug-resistant and extensively drug-resistant tuberculosis. J Antimicrob Chemother 2009; 64: 388–91PubMedCrossRef
97.
Williams KN, Brickner SJ, Stover CK, et al. Addition of PNU-100480 to first-line drugs shortens the time needed to cure murine tuberculosis. Am J Respir Crit Care Med 2009 Aug 15; 180(4): 371–6PubMedCrossRef
98.
Pfizer. Safety, tolerability, pharmacokinetics and measurement of whole blood activity (WBA) of PNU-100480 after multiple oral doses in healthy adult volunteers [ClinicalTrials.gov identifier: NCT00990990]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
99.
Wallis RS, Jakubiec WM, Kumar V, et al. Pharmacokinetics and whole-blood bactericidal activity against Mycobacterium tuberculosis of single doses of PNU-100480 in healthy volunteers. J Infect Dis 2010; 202(5): 745–51PubMedCrossRef
100.
AstraZeneca. A study in healthy volunteers to assess safety and blood levels of AZD5847 after multiple doses over 14 days [ClinicalTrials.gov identifier NCT01116258]. US National Institutes of Health, ClinicalTrials.gov [online]. Available from URL: http://​www.​clinicaltrials.​gov [Accessed 2010 Jun 28]
101.
Ma Z, Lienhardt C. Drugs in clinical trials and in preclinical development. Clin Chest Med 2009 Dec; 30(4): 755–68PubMedCrossRef
102.
Rivero-Lezcano OM. Cytokines as immunomodulators in tuberculosis therapy. Recent Pat Antiinfect Drug Discov 2008 Nov; 3(3): 168–76PubMedCrossRef
103.
Zaitzeva SI, Matveeva SL, Gerasimova TG, et al. Treatment of cavitary and infiltrating pulmonary tuberculosis with and without the immunomodulator dzherelo. Clin Microbiol Infect 2009 Dec; 15(12): 1154–62PubMedCrossRef
104.
Dlugovitzky D, Fiorenza G, Farroni M, et al. Immunological consequences of three doses of heat-killed mycobacterium vaccae in the immunotherapy of tuberculosis. Respir Med 2006 Jun; 100(6): 1079–87PubMedCrossRef
105.
Stanford J, Stanford C, Grange J. Immunotherapy with mycobacterium vaccae in the treatment of tuberculosis. Front Biosci 2004 May 1; 9: 1701–19PubMedCrossRef
106.
Vilaplana C, Montané E, Pinto S, et al. Double-blind, randomized, placebo-controlled phase I clinical trial of the therapeutical antituberculous vaccine RUTI. Vaccine 2010 Jan 22; 28(4): 1106–16PubMedCrossRef
107.
Kaufmann SH, Hussey G, Lambert P-H. New vaccines for tuberculosis. Lancet 2010 Jun 12; 375(9731): 2110–9PubMedCrossRef
108.
Lambert PH, Hawkridge T, Hanekom WA. New vaccines against tuberculosis. Clin Chest Med 2009 Dec; 30(4): 811–26PubMedCrossRef
109.
Skeiky YA, Dietrich J, Lasco TM, et al. Non-clinical efficacy and safety of HyVac4:IC31 vaccine administered in a BCG prime-boost regimen. Vaccine 2010; 28(4): 1084–93PubMedCrossRef
110.
Parida SK, Kaufmann SH. The quest for biomarkers in tuberculosis. Drug Discov Today 2010 Feb; 15(3–4): 148–57PubMedCrossRef
111.
Wallis RS, Pai M, Menzies D, et al. Biomarkers and diagnostics for tuberculosis: progress, needs, and translation into practice. Lancet 2010 May 29; 375(9729): 1920–37PubMedCrossRef
112.
Lönnroth K, Castro KG, Chakaya JM, et al. Tuberculosis control and elimination 2010–50: cure, care, and social development. Lancet 2010 May 22; 375(9728): 1814–29PubMedCrossRef
Metadata
Title
Drugs in Development for Tuberculosis
Author
Dr Ann M. Ginsberg, MD, PhD
Publication date
01-12-2010
Publisher
Springer International Publishing
Published in
Drugs / Issue 17/2010
Print ISSN: 0012-6667
Electronic ISSN: 1179-1950
DOI
https://doi.org/10.2165/11538170-000000000-00000

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