High-dose rifampicin kills persisters, shortens treatment duration, and reduces relapse rate in vitro and in vivo

Frontiers in Microbiology

Volumn 6, Issue JUN, 2015, Pages

  Hu, Yanmin ^a   Liu, Alexander ^b   Ortega Muro, Fatima ^c   Alameda Martin, Laura ^c   Mitchison, Denis ^a   Coates, Anthony ^a  

^a ST GEORGE S HOSPITAL   (United Kingdom)

^b UNIVERSITY OF OXFORD   (United Kingdom)

^c GLAXOSMITHKLINE   (Spain)

Author keywords

Mouse model; Mycobacterium tuberculosis; Persistence; Resuscitation promoting factors; Rifampicin

Indexed keywords

ISONIAZID; PYRAZINAMIDE; RIFAMPICIN;

ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC RESISTANCE; ARTICLE; BACTERIAL GROWTH; BACTERIUM CULTURE; BLOOD SAMPLING; CONTROLLED STUDY; DRUG EFFICACY; DRUG MEGADOSE; FEMALE; HYPOXIA; MOUSE; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; STATISTICAL ANALYSIS; TREATMENT DURATION; TREATMENT OUTCOME; TUBERCULOSIS;

MURINAE; MUS; MYCOBACTERIUM TUBERCULOSIS;

EID: 84937157202     PISSN: None     EISSN: 1664302X     Source Type: Journal    
DOI: 10.3389/fmicb.2015.00641     Document Type: Article

References (39)

1. Abdool Karim, S. S., Naidoo, K., Grobler, A., Padayatchi, N., Baxter, C., Gray, A., et al. (2010). Timing of initiation of antiretroviral drugs during tuberculosis therapy. N. Engl. J. Med. 362, 697-706. doi: 10.1056/NEJMoa0905848
2. Boeree, M. J., Diacon, A., Dawson, R., Van Balen, G. P., Venter, A., Du Bois, J., et al. (2013). What is the Right Dose of Rifampin? A Dose Escalating Study. Available at: http://www.atsjournals.org/doi/abs/10.1164/ajrccm-conference.2013.187.1_MeetingAbstracts.A3181
3. Calver, A. D., Falmer, A. A., Murray, M., Strauss, O. J., Streicher, E. M., Hanekom, M., et al. (2010). Emergence of increased resistance and extensively drug-resistant tuberculosis despite treatment adherence, South Africa. Emerg. Infect. Dis. 16, 264-271. doi: 10.3201/eid1602.090968
4. Coates, A. R., Hu, Y., Jindani, A., and Mitchison, D. A. (2013). Contradictory results with high-dosage rifamycin in mice and humans. Antimicrob. Agents Chemother. 57, 1103. doi: 10.1128/AAC.01705-12
5. de Steenwinkel, J. E., Aarnoutse, R. E., de Knegt, G. J., Ten Kate, M. T., Teulen, M., Verbrugh, H. A., et al. (2013). Optimization of the rifampin dosage to improve the therapeutic efficacy in tuberculosis treatment, using a murine model. Am. J. Respir. Crit. Care Med. 187, 1127-1134. doi: 10.1164/rccm.201207-1210OC
6. de Steenwinkel, J. E., de Knegt, G. J., ten Kate, M. T., van Belkum, A., Verbrugh, H. A., Kremer, K., et al. (2010). Time-kill kinetics of anti-tuberculosis drugs, and emergence of resistance, in relation to metabolic activity of Mycobacterium tuberculosis. J. Antimicrob. Chemother. 65, 2582-2589. doi: 10.1093/jac/dkq374
7. Diacon, A. H., Patientia, R. F., Venter, A., van Helden, P. D., Smith, P. J., McIlleron, H., et al. (2007). Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob. Agents Chemother. 51, 2994-2996. doi: 10.1128/AAC.01474-06
8. Doble, N., Shaw, R., Rowland-Hill, C., Lush, M., Warnock, D. W., and Keal, E. E. (1988). Pharmacokinetic study of the interaction between rifampicin and ketoconazole. J. Antimicrob. Chemother. 21, 633-635. doi: 10.1093/jac/21.5.633
9. Gill, W. P., Harik, N. S., Whiddon, M. R., Liao, R. P., Mittler, J. E., and Sherman, D. R. (2009). A replication clock for Mycobacterium tuberculosis. Nat. Med. 15, 211-214. doi: 10.1038/nm.1915
10. Girling, D. J. (1978). The hepatic toxicity of antituberculosis regimens containing isoniazid, rifampicin and pyrazinamide. Tubercle 59, 13-32. doi: 10.1016/0041-3879(77)90022-8
11. Gumbo, T., Louie, A., Deziel, M. R., Liu, W., Parsons, L. M., Salfinger, M., et al. (2007). Concentration-dependent Mycobacterium tuberculosis killing and prevention of resistance by rifampin. Antimicrob. Agents Chemother. 51, 3781-3788. doi: 10.1128/AAC.01533-06
12. Hu, Y., Butcher, P. D., Mangan, J. A., Rajandream, M. A., and Coates, A. R. (1999). Regulation of hmp gene transcription in Mycobacterium tuberculosis: effects of oxygen limitation and nitrosative and oxidative stress. J. Bacteriol. 181, 3486-3493.
13. Hu, Y. M., Butcher, P. D., Sole, K., Mitchison, D. A., and Coates, A. R. (1998). Protein synthesis is shutdown in dormant Mycobacterium tuberculosis and is reversed by oxygen or heat shock. FEMS Microbiol. Lett. 158, 139-145. doi: 10.1111/j.1574-6968.1998.tb12813.x
14. Hu, Y., and Coates, A. R. (2009). Acute and persistent Mycobacterium tuberculosis infections depend on the thiol peroxidase TPX. PLoS ONE 4:e5150. doi: 10.1371/journal.pone.0005150
15. Hu, Y., Mangan, J. A., Dhillon, J., Sole, K. M., Mitchison, D. A., Butcher, P. D., et al. (2000). Detection of mRNA transcripts and active transcription in persistent Mycobacterium tuberculosis induced by exposure to rifampin or pyrazinamide. J. Bacteriol. 182, 6358-6365. doi: 10.1128/JB.182.22.6358-6365.2000
16. Hu, Y., Movahedzadeh, F., Stoker, N. G., and Coates, A. R. (2006). Deletion of the Mycobacterium tuberculosis alpha-crystallin-like hspX gene causes increased bacterial growth in vivo. Infect. Immun. 74, 861-868. doi: 10.1128/IAI.74.2.861-868.2006
17. Jayaram, R., Gaonkar, S., Kaur, P., Suresh, B. L., Mahesh, B. N., Jayashree, R., et al. (2003). Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob. Agents Chemother. 47, 2118-2124. doi: 10.1128/AAC.47.7.2118-2124.2003
18. Kreis, B., Pretet, S., Birenbaum, J., Guibout, P., Hazeman, J. J., Orin, E., et al. (1976). Two three-month treatment regimens for pulmonary tuberculosis. Bull. Int. Union Tuberc. 51, 71-75.
19. McCune, R. M., Feldmann, F. M., Lambert, H. P., and McDermott, W. (1966). Microbial persistence. I. The capacity of tubercle bacilli to survive sterilization in mouse tissues. J. Exp. Med. 123, 445-468. doi: 10.1084/jem.123.3.445
20. McCune, R. M. Jr., and Tompsett, R. (1956). 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. doi: 10.1084/jem.104.5.737
21. Mitchison, D. A. (1985). The action of antituberculosis drugs in short-course chemotherapy. Tubercle 66, 219-225. doi: 10.1016/0041-3879(85)90040-6
22. Mitchison, D. A. (1998). Development of rifapentine: the way ahead. Int. J. Tuberc. Lung Dis. 2, 612-615.
23. Mitchison, D. A. (2000). Role of individual drugs in the chemotherapy of tuberculosis. Int. J. Tuberc. Lung Dis. 4, 796-806.
24. Mitchison, D. A. (2005). Shortening the treatment of tuberculosis. Nat. Biotechnol. 23, 187-188. doi: 10.1038/nbt0205-187
25. Mitchison, D. A. (2012). Pharmacokinetic/pharmacodynamic parameters and the choice of high-dosage rifamycins. Int. J. Tuberc. Lung Dis. 16, 1186-1189. doi: 10.5588/ijtld.11.0818
26. Mitchison, D. A., and Fourie, P. B. (2010). The near future: improving the activity of rifamycins and pyrazinamide. Tuberculosis (Edinb.) 90, 177-181. doi: 10.1016/j.tube.2010.03.005
27. Mukamolova, G. V., Kaprelyants, A. S., Young, D. I., Young, M., and Kell, D. B. (1998). A bacterial cytokine. Proc. Natl. Acad. Sci. U.S.A. 95, 8916-8921. doi: 10.1073/pnas.95.15.8916
28. Mukamolova, G. V., Turapov, O., Malkin, J., Woltmann, G., and Barer, M. R. (2010). Resuscitation-promoting factors reveal an occult population of tubercle Bacilli in Sputum. Am. J. Respir. Crit. Care Med. 181, 174-180. doi: 10.1164/rccm.200905-0661OC
29. Nunn, A. J., Phillips, P. P., and Gillespie, S. H. (2008). Design issues in pivotal drug trials for drug sensitive tuberculosis (TB). Tuberculosis (Edinb.) 88(Suppl. 1), S85-S92. doi: 10.1016/S1472-9792(08)70039-8
30. Pasipanodya, J. G., McIlleron, H., Burger, A., Wash, P. A., Smith, P., and Gumbo, T. (2013). Serum drug concentrations predictive of pulmonary tuberculosis outcomes. J. Infect. Dis. 208, 1464-1473. doi: 10.1093/infdis/jit352
31. Rosenthal, I. M., Tasneen, R., Peloquin, C. A., Zhang, M., Almeida, D., Mdluli, K. E., et al. (2012). Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob. Agents Chemother. 56, 4331-4340. doi: 10.1128/AAC.00912-12
32. Shleeva, M. O., Bagramyan, K., Telkov, M. V., Mukamolova, G. V., Young, M., Kell, D. B., et al. (2002). Formation and resuscitation of "non-culturable" cells of Rhodococcus rhodochrous and Mycobacterium tuberculosis in prolonged stationary phase. Microbiology (Read. Engl.) 148, 1581-1591.
33. Sirgel, F. A., Fourie, P. B., Donald, P. R., Padayatchi, N., Rustomjee, R., Levin, J., et al. (2005). The early bactericidal activities of rifampin and rifapentine in pulmonary tuberculosis. Am. J. Respir. Crit. Care Med. 172, 128-135. doi: 10.1164/rccm.200411-1557OC
34. van Niekerk, C., and Ginsberg, A. (2009). Assessment of global capacity to conduct tuberculosis drug development trials: do we have what it takes? Int. J. Tuberc. Lung Dis. 13, 1367-1372.
35. Wayne, L. G. (1976). Dynamics of submerged growth of Mycobacterium tuberculosis under aerobic and microaerophilic conditions. Am. Rev. Respir. Dis. 114, 807-811.
36. Wayne, L. G. (1977). Synchronized replication of Mycobacterium tuberculosis. Infect. Immun. 17, 528-530.
37. Wayne, L. G. (1994). Dormancy of Mycobacterium tuberculosis and latency of disease. Eur. J. Clin. Microbiol. Infect. Dis. 13, 908-914. doi: 10.1007/BF02111491
38. World Health Organization [WHO]. (2010). WHO global tuberculosis control report 2010. Summary. Cent. Eur. J. Public Health 18, 237.
39. Yew, W. W., and Leung, C. C. (2006). Antituberculosis drugs and hepatotoxicity. Respirology 11, 699-707. doi: 10.1111/j.1440-1843.2006.00941.x