Bactericidal activity of pyrazinamide and clofazimine alone and in combinations with pretomanid and bedaquiline

American Journal of Respiratory and Critical Care Medicine

Volumn 191, Issue 8, 2015, Pages 943-953

  Diacon, Andreas H ^a,b,e   Dawson, Rodney ^c   Von Groote Bidlingmaier, Florian ^b   Symons, Gregory ^c   Venter, Amour ^d   Donald, Peter R ^e   Van Niekerk, Christo ^f   Everitt, Daniel ^g   Hutchings, Jane ^f   Burger, Divan A ^h,i   Schall, Robert ^h,i   Mendel, Carl M ^g  

^a SOUTH AFRICAN MEDICAL RESEARCH COUNCIL   (South Africa)

^b TASK APPLIED SCIENCE   (South Africa)

^c UNIVERSITY OF CAPE TOWN   (South Africa)

^d STELLENBOSCH UNIVERSITY   (South Africa)

^e UNIVERSITY OF STELLENBOSCH   (South Africa)

^f Global Alliance for TB Drug Development   (South Africa)

^g GLOBAL ALLIANCE FOR TB DRUG DEVELOPMENT   (United States)

^h UNIVERSITY OF THE FREE STATE   (South Africa)

ⁱ IQVIA   (United States)

Author keywords

Antitubercular agents; Drug evaluation; Tuberculosis

Indexed keywords

BEDAQUILINE; CLOFAZIMINE; PRETOMANID; PYRAZINAMIDE; 2-NITRO-6-(4-(TRIFLUOROMETHOXY)BENZYLOXY)-6,7-DIHYDRO-5H-IMIDAZO(2,1-B)(1,3)OXAZINE; NITROIMIDAZOLE DERIVATIVE; QUINOLINE DERIVATIVE; TUBERCULOSTATIC AGENT;

ADULT; AREA UNDER THE CURVE; ARTICLE; BACTERICIDAL ACTIVITY; COLONY FORMING UNIT; CONTROLLED STUDY; DRUG BLOOD LEVEL; DRUG HALF LIFE; DRUG METABOLISM; DRUG POTENCY; DRUG RESISTANT TUBERCULOSIS; DRUG SAFETY; DRUG TOLERABILITY; FEMALE; HUMAN; HUMAN IMMUNODEFICIENCY VIRUS; LUNG TUBERCULOSIS; MAJOR CLINICAL STUDY; MALE; MAXIMUM PLASMA CONCENTRATION; MINIMUM INHIBITORY CONCENTRATION; MINIMUM PLASMA CONCENTRATION; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; OPEN STUDY; PHASE 2 CLINICAL TRIAL; PLASMA CONCENTRATION-TIME CURVE; PRIORITY JOURNAL; RANDOMIZED CONTROLLED TRIAL; SOUTH AFRICA; SPUTUM CYTODIAGNOSIS; TIME TO MAXIMUM PLASMA CONCENTRATION; TREATMENT DURATION; CLINICAL TRIAL; COMPLICATION; DRUG COMBINATION; HUMAN IMMUNODEFICIENCY VIRUS INFECTION; MULTICENTER STUDY; PROCEDURES; TREATMENT OUTCOME; TUBERCULOSIS; TUBERCULOSIS, MULTIDRUG-RESISTANT;

ADULT; ANTITUBERCULAR AGENTS; CLOFAZIMINE; DIARYLQUINOLINES; DRUG THERAPY, COMBINATION; FEMALE; HIV INFECTIONS; HUMANS; MALE; NITROIMIDAZOLES; PYRAZINAMIDE; TREATMENT OUTCOME; TUBERCULOSIS; TUBERCULOSIS, MULTIDRUG-RESISTANT;

EID: 84924312173     PISSN: 1073449X     EISSN: 15354970     Source Type: Journal    
DOI: 10.1164/rccm.201410-1801OC     Document Type: Article

References (33)

1. World Health Organization. Global tuberculosis report. 2014 [accessed 2015 Feb 24]. Available from: http://www.who.int/tb/publications/global-report/en/
2. Ibrahim M, Andries K, Lounis N, Chauffour A, Truffot-Pernot C, Jarlier V, Veziris N. Synergistic activity of R207910 combined with pyrazinamide against murine tuberculosis. Antimicrob Agents Chemother 2007;51: 1011-1015.
3. Tasneen R, Tyagi S, Williams K, Grosset J, Nuermberger E. Enhanced bactericidal activity of rifampin and/or pyrazinamide when combined with PA-824 in a murine model of tuberculosis. Antimicrob Agents Chemother 2008;52:3664-3668.
4. Williams K, Minkowski A, Amoabeng O, Peloquin CA, Taylor D, Andries K, Wallis RS, Mdluli KE, Nuermberger EL. Sterilizing activities of novel combinations lacking first- and second-line drugs in a murine model of tuberculosis. Antimicrob Agents Chemother 2012;56: 3114-3120.
5. Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Winter H, Becker P, et al. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet 2012; 380:986-993.
6. Van Deun A, Maug AK, Salim MA, Das PK, Sarker MR, Daru P, Rieder HL. Short, highly effective, and inexpensive standardized treatment of multidrugresistant tuberculosis. Am J Respir Crit Care Med 2010;182:684-692.
7. Diacon A, Dawson R, Van Niekerk C, Hutchings J, Murray S, Schall R, Burger D, Everitt D, Mendel C. 14 day EBA study of PA-824, bedaquiline, pyrazinamide and clofazimine in smear positive TB patients. Presented at the Conference on Retroviruses and Opportunistic Infections (CROI). March 3-6, 2014, Boston, MA.
8. International Union against Tuberculosis and Lung Disease. Laboratory diagnosis of tuberculosis by sputum microscopy: the handbook. 2013 [accessed 2015 Feb 24]. Available from: http://www.theunion.org/what-we-do/publications/technical/laboratory-diagnosis-oftuberculosis-by-sputum-microscopy-the-handbook
9. Fridericia L. The duration of systole in the electrocardiogram of normal subjects and of patients with heart disease. Acta Med Scand 1920;53: 469-486.
10. Bazett HC. The time relations of the blood-pressure changes after excision of the adrenal glands, with some observations on blood volume changes. J Physiol 1920;53:320-339.
11. Donald PR, Diacon AH. The early bactericidal activity of antituberculosis drugs: a literature review. Tuberculosis (Edinb) 2008;88: S75-S83.
12. Diacon A, Maritz JS, Donald P. Early bactericidal activity of antituberculosis agents. In: Donald PR, Van Helden PD, editors. Antituberculosis chemotherapy. Basel: Karger; 2011. pp. 213-219.
13. Warren RM, Gey van Pittius NC, Barnard M, Hesseling A, Engelke E, de Kock M, Gutierrez MC, Chege GK, Victor TC, Hoal EG, et al. Differentiation of Mycobacterium tuberculosis complex by PCR amplification of genomic regions of difference. Int J Tuberc Lung Dis 2006;10:818-822.
14. Burger DA, Schall R. A Bayesian non-linear mixed effects regression model for the characterization of early bactericidal activity of tuberculosis drugs. J Biopharm Stat [online ahead of print] 16 Oct 2014; DOI: 10.1080/10543406.2014.971170.
15. Davies GR, Brindle R, Khoo SH, Aarons LJ. Use of nonlinear mixedeffects analysis for improved precision of early pharmacodynamic measures in tuberculosis treatment. Antimicrob Agents Chemother 2006;50:3154-3156.
16. Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK. Assessment of the effects of the nitroimidazo-oxazine PA-824 on renal function in healthy subjects. Antimicrob Agents Chemother 2009;53:3726-3733.
17. Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK. Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects. Antimicrob Agents Chemother 2009;53:3720-3725.
18. Diacon AH, Dawson R, du Bois J, Narunsky K, Venter A, Donald PR, van Niekerk C, Erondu N, Ginsberg AM, Becker P, et al. Phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob Agents Chemother 2012;56:3027-3031.
19. Diacon AH, Dawson R, Hanekom M, Narunsky K, Maritz SJ, Venter A, Donald PR, van Niekerk C, Whitney K, Rouse DJ, et al. Early bactericidal activity and pharmacokinetics of PA-824 in smearpositive tuberculosis patients. Antimicrob Agents Chemother 2010; 54:3402-3407.
20. Diacon AH, Dawson R, Von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, Conradie A, Erondu N, Ginsberg AM, Egizi E, et al. Randomized dose-ranging study of the 14-day early bactericidal activity of bedaquiline (TMC207) in patients with sputum microscopy smear-positive pulmonary tuberculosis. Antimicrob Agents Chemother 2013;57:2199-2203.
21. Donald PR, Maritz JS, Diacon AH. Pyrazinamide pharmacokinetics and efficacy in adults and children. Tuberculosis (Edinb) 2012;92:1-8.
22. Nix DE, Adam RD, Auclair B, Krueger TS, Godo PG, Peloquin CA. Pharmacokinetics and relative bioavailability of clofazimine in relation to food, orange juice and antacid. Tuberculosis (Edinb) 2004;84:365-373.
23. Jindani A, Aber VR, Edwards EA, Mitchison DA. The early bactericidal activity of drugs in patients with pulmonary tuberculosis. Am Rev Respir Dis 1980;121:939-949.
24. Kayigire XA, Friedrich SO, Venter A, Dawson R, Gillespie SH, Boeree MJ, Heinrich N, Hoelscher M, Diacon AH; Pan African Consortium for the Evaluation of Anti-Tuberculosis Antibiotics. Direct comparison of Xpert MTB/RIF assay with liquid and solid mycobacterial culture for quantification of early bactericidal activity. J Clin Microbiol 2013; 51:1894-1898.
25. Reddy VM, Nadadhur G, Daneluzzi D, O'Sullivan JF, Gangadharam PR. Antituberculosis activities of clofazimine and its new analogs B4154 and B4157. Antimicrob Agents Chemother 1996;40:633-636.
26. Grosset JH, Tyagi S, Almeida DV, Converse PJ, Li SY, Ammerman NC, Bishai WR, Enarson D, Trébucq A. Assessment of clofazimine activity in a second-line regimen for tuberculosis in mice. Am J Respir Crit Care Med 2013;188:608-612.
27. Janulionis E, Sofer C, Song HY, Wallis RS. Lack of activity of orally administered clofazimine against intracellular Mycobacterium tuberculosis in whole-blood culture. Antimicrob Agents Chemother 2004;48:3133-3135.
28. Cholo MC, Steel HC, Fourie PB, Germishuizen WA, Anderson R. Clofazimine: current status and future prospects. J Antimicrob Chemother 2012;67:290-298.
29. Hwang TJ, Dotsenko S, Jafarov A, Weyer K, Falzon D, Lunte K, Nunn P, Jaramillo E, Keshavjee S, Wares DF. Safety and availability of clofazimine in the treatment of multidrug and extensively drugresistant tuberculosis: analysis of published guidance and metaanalysis of cohort studies. BMJ Open 2014;4:e004143.
30. Schaad-Lanyi Z, Dieterle W, Dubois JP, Theobald W, Vischer W. Pharmacokinetics of clofazimine in healthy volunteers. Int J Lepr Other Mycobact Dis 1987;55:9-15.
31. Bezerra EL, Vilar MJ, da Trindade Neto PB, Sato EI. Double-blind, randomized, controlled clinical trial of clofazimine compared with chloroquine in patients with systemic lupus erythematosus. Arthritis Rheum 2005;52:3073-3078.
32. Ren YR, Pan F, Parvez S, Fleig A, Chong CR, Xu J, Dang Y, Zhang J, Jiang H, Penner R, et al. Clofazimine inhibits human Kv1.3 potassium channel by perturbing calcium oscillation in T lymphocytes. PLoS One 2008;3:e4009.
33. Dannemann BR, Bakare N, De Marez T, Lounis N, Van Heeswijk R, Meyvisch P, Haxaire M, Andries K, Everitt D, Upton A. Corrected QT interval (QTcF) prolongation in a phase 2 open-label trial of TMC207 plus background regimen as treatment for MDR-TB: effect of coadministration with clofazimine. Presented at the Interscience Conference on Antimicrobial Agents and Chemotherapy (ICAAC). September 9-13, 2013 [accessed 2015 Feb 24], Denver, CO. Abstract A-1259. Available from: http://icaaconline.com/php/icaac2013abstracts/data/papers/2012/A/2012-A-1259.htm