Potent rifamycin-sparing regimen cures guinea pig tuberculosis as rapidly as the standard regimen

Antimicrobial Agents and Chemotherapy

Volumn 57, Issue 8, 2013, Pages 3910-3916

  Dutta, Noton K ^a   Alsultan, Abdullah ^b   Gniadek, Thomas J ^a   Belchis, Deborah A ^a   Pinn, Michael L ^a   Mdluli, Khisimuzi E ^c   Nuermberger, Eric L ^a,d   Peloquin, Charles A ^b   Karakousis, Petros C ^a,d  

^a JOHNS HOPKINS UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF FLORIDA HEALTH   (United States)

^c Global Alliance for TB Drug Development   (United States)

^d JOHNS HOPKINS BLOOMBERG SCHOOL OF PUBLIC HEALTH   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

6,7 DIHYDRO 2 NITRO 6 (4 TRIFLUOROMETHOXYBENZYLOXY) 5H IMIDAZO[2,1 B][1,3]OXAZINE; ISONIAZID; MOXIFLOXACIN; PYRAZINAMIDE; RIFAMPICIN; RIFAMYCIN;

AEROSOL; ANIMAL EXPERIMENT; ANIMAL MODEL; ANTIBIOTIC THERAPY; AREA UNDER THE CURVE; ARTICLE; BACTERICIDAL ACTIVITY; COMPARATIVE STUDY; DRUG POTENCY; EXPERIMENTAL GUINEA PIG; GRANULOMA; LUNG WEIGHT; MAXIMUM PLASMA CONCENTRATION; MINIMUM INHIBITORY CONCENTRATION; MORBIDITY; MORTALITY; MYCOBACTERIUM TUBERCULOSIS; NONHUMAN; PRIORITY JOURNAL; RECURRENCE RISK; RELAPSE; SPLEEN WEIGHT; STEADY STATE; TUBERCULOSIS;

ANIMALS; ANTITUBERCULAR AGENTS; AREA UNDER CURVE; DISEASE MODELS, ANIMAL; DRUG EVALUATION, PRECLINICAL; DRUG THERAPY, COMBINATION; FEMALE; GUINEA PIGS; LUNG; MYCOBACTERIUM TUBERCULOSIS; NITROIMIDAZOLES; ORGAN SIZE; PYRAZINAMIDE; RECURRENCE; RIFAMYCINS; TUBERCULOSIS, MULTIDRUG-RESISTANT; TUBERCULOSIS, PULMONARY;

EID: 84880292737     PISSN: 00664804     EISSN: 10986596     Source Type: Journal    
DOI: 10.1128/AAC.00761-13     Document Type: Article

References (52)

1. Ma Z, Lienhardt C, McIlleron H, Nunn AJ, Wang X. 2010. Global tuberculosis drug development pipeline: the need and the reality. Lancet 375:2100-2109.
2. Dutta NK, Karakousis PC. 2012. Tuberculosis chemotherapy: present situation, possible solutions, and progress towards a TB-free world. Indian J. Med. Microbiol. 30:261-263.
3. Nuermberger E, Tyagi S, Tasneen R, Williams KN, Almeida D, Rosenthal I, Grosset JH. 2008. Powerful bactericidal and sterilizing activity of a regimen containing PA-824, moxifloxacin, and pyrazinamide in a murine model of tuberculosis. Antimicrob. Agents Chemother. 52: 1522-1524.
4. Nuermberger EL, Yoshimatsu T, Tyagi S, Williams K, Rosenthal I, O'Brien RJ, Vernon AA, Chaisson RE, Bishai WR, Grosset JH. 2004. Moxifloxacin-containing regimens of reduced duration produce a stable cure in murine tuberculosis. Am. J. Respir. Crit. Care Med. 170:1131-1134.
5. Tasneen R, Li SY, Peloquin CA, Taylor D, Williams KN, Andries K, Mdluli KE, Nuermberger EL. 2011. Sterilizing activity of novel TMC207-and PA-824-containing regimens in a murine model of tuberculosis. Antimicrob. Agents Chemother. 55:5485-5492.
6. Williams K, Minkowski A, Amoabeng O, Peloquin CA, Taylor D, Andries K, Wallis RS, Mdluli KE, Nuermberger EL. 2012. Sterilizing activities of novel combinations lacking first-and second-line drugs in a murine model of tuberculosis. Antimicrob. Agents Chemother. 56:3114-3120.
7. Tasneen R, Tyagi S, Williams K, Grosset J, Nuermberger E. 2008. Enhanced bactericidal activity of rifampin and/or pyrazinamide when combined with PA-824 in a murine model of tuberculosis. Antimicrob. Agents Chemother. 52:3664-3668.
8. Diacon AH, Dawson R, von Groote-Bidlingmaier F, Symons G, Venter A, Donald PR, van Niekerk C, Everitt D, Winter H, Becker P, Mendel CM, Spigelman MK. 2012. 14-day bactericidal activity of PA-824, bedaquiline, pyrazinamide, and moxifloxacin combinations: a randomised trial. Lancet 380:986-993.
9. Ahmad Z, Nuermberger EL, Tasneen R, Pinn ML, Williams KN, Peloquin CA, Grosset JH, Karakousis PC. 2010. Comparison of the 'Denver regimen' against acute tuberculosis in the mouse and guinea pig. J. Antimicrob. Chemother. 65:729-734.
10. Dutta NK, Illei PB, Peloquin CA, Pinn ML, Mdluli KE, Nuermberger EL, Grosset JH, Karakousis PC. 2012. Rifapentine is not more active than rifampin against chronic tuberculosis in guinea pigs. Antimicrob. Agents Chemother. 56:3726-3731.
11. Ahmad Z, Fraig MM, Pinn ML, Tyagi S, Nuermberger EL, Grosset JH, Karakousis PC. 2011. Effectiveness of tuberculosis chemotherapy correlates with resistance to Mycobacterium tuberculosis infection in animal models. J. Antimicrob. Chemother. 66:1560-1566.
12. Ahmad Z, Fraig MM, Bisson GP, Nuermberger EL, Grosset JH, Karakousis PC. 2011. Dose-dependent activity of pyrazinamide in animal models of intracellular and extracellular tuberculosis infections. Antimicrob. Agents Chemother. 55:1527-1532.
13. Ahmad Z, Pinn ML, Nuermberger EL, Peloquin CA, Grosset JH, Karakousis PC. 2010. The potent bactericidal activity of streptomycin in the guinea pig model of tuberculosis ceases due to the presence of persisters. J. Antimicrob. Chemother. 65:2172-2175.
14. Ahmad Z, Klinkenberg LG, Pinn ML, Fraig MM, Peloquin CA, Bishai WR, Nuermberger EL, Grosset JH, Karakousis PC. 2009. Biphasic kill curve of isoniazid reveals the presence of drug-tolerant, not drugresistant, Mycobacterium tuberculosis in the guinea pig. J. Infect. Dis. 200:1136-1143.
15. Sanchez F, Lopez Colomes JL, Villarino E, Grosset J. 2011. New drugs for tuberculosis treatment. Enferm. Infecc. Microbiol. Clin. 29(Suppl 1): 47-56.
16. Srivastava S, Gumbo T. 2011. In vitro and in vivo modeling of tuberculosis drugs and its impact on optimization of doses and regimens. Curr. Pharm. Des. 17:2881-2888.
17. Garcia-Contreras L, Sung JC, Muttil P, Padilla D, Telko M, Verberkmoes JL, Elbert KJ, Hickey AJ, Edwards DA. 2010. Dry powder PA-824 aerosols for treatment of tuberculosis in guinea pigs. Antimicrob. Agents Chemother. 54:1436-1442.
18. Karakousis PC, Williams EP, Bishai WR. 2008. Altered expression of isoniazid-regulated genes in drug-treated dormant Mycobacterium tuberculosis. J. Antimicrob. Chemother. 61:323-331.
19. Dutta NK, Alsultan A, Peloquin CA, Karakousis PC. 2013. Preliminary pharmacokinetic study of repeated doses of rifampin and rifapentine in guinea pigs. Antimicrob. Agents Chemother. 57:1535-1537.
20. Sung JC, Garcia-Contreras L, Verberkmoes JL, Peloquin CA, Elbert KJ, Hickey AJ, Edwards DA. 2009. Dry powder nitroimidazopyran antibiotic PA-824 aerosol for inhalation. Antimicrob. Agents Chemother. 53:1338-1343.
21. Nuermberger E, Rosenthal I, Tyagi S, Williams KN, Almeida D, Peloquin CA, Bishai WR, Grosset JH. 2006. Combination chemotherapy with the nitroimidazopyran PA-824 and first-line drugs in a murine model of tuberculosis. Antimicrob. Agents Chemother. 50:2621-2625.
22. Johnson JL, Hadad DJ, Boom WH, Daley CL, Peloquin CA, Eisenach KD, Jankus DD, Debanne SM, Charlebois ED, Maciel E, Palaci M, Dietze R. 2006. Early and extended early bactericidal activity of levofloxa-cin, gatifloxacin and moxifloxacin in pulmonary tuberculosis. Int. J. Tuberc. Lung Dis. 10:605-612.
23. Peloquin CA, Hadad DJ, Molino LP, Palaci M, Boom WH, Dietze R, Johnson JL. 2008. Population pharmacokinetics of levofloxacin, gatifloxacin, and moxifloxacin in adults with pulmonary tuberculosis. Antimicrob. Agents Chemother. 52:852-857.
24. Rosenthal IM, Williams K, Tyagi S, Vernon AA, Peloquin CA, Bishai WR, Grosset JH, Nuermberger EL. 2005. Weekly moxifloxacin and rifapentine is more active than the Denver regimen in murine tuberculosis. Am. J. Respir. Crit. Care Med. 172:1457-1462.
25. Klinkenberg LG, Sutherland LA, Bishai WR, Karakousis PC. 2008. Metronidazole lacks activity against Mycobacterium tuberculosis in an in vivo hypoxic granuloma model of latency. J. Infect. Dis. 198:275-283.
26. Grosset J, Truffot-Pernot C, Lacroix C, Ji B. 1992. Antagonism between isoniazid and the combination pyrazinamide-rifampin against tuberculosis infection in mice. Antimicrob. Agents Chemother. 36:548-551.
27. Dhillon J, Dickinson JM, Sole K, Mitchison DA. 1996. Preventive chemotherapy of tuberculosis in Cornell model mice with combinations of rifampin, isoniazid, and pyrazinamide. Antimicrob. Agents Chemother. 40:552-555.
28. Ginsberg AM, Laurenzi MW, Rouse DJ, Whitney KD, Spigelman MK. 2009. Safety, tolerability, and pharmacokinetics of PA-824 in healthy subjects. Antimicrob. Agents Chemother. 53:3720-3725.
29. Diacon AH, Dawson R, du Bois J, Narunsky K, Venter A, Donald PR, van Niekerk C, Erondu N, Ginsberg AM, Becker P, Spigelman MK. 2012. Phase II dose-ranging trial of the early bactericidal activity of PA-824. Antimicrob. Agents Chemother. 56:3027-3031.
30. Ahmad Z, Peloquin CA, Singh RP, Derendorf H, Tyagi S, Ginsberg A, Grosset JH, Nuermberger EL. 2011. PA-824 exhibits time-dependent activity in a murine model of tuberculosis. Antimicrob. Agents Chemother. 55:239-245.
31. Diacon AH, Dawson R, Hanekom M, Narunsky K, Maritz SJ, Venter A, Donald PR, van Niekerk C, Whitney K, Rouse DJ, Laurenzi MW, Ginsberg AM, Spigelman MK. 2010. Early bactericidal activity and pharmacokinetics of PA-824 in smear-positive tuberculosis patients. Antimicrob. Agents Chemother. 54:3402-3407.
32. Singh R, Manjunatha U, Boshoff HI, Ha YH, Niyomrattanakit P, Ledwidge R, Dowd CS, Lee IY, Kim P, Zhang L, Kang S, Keller TH, Jiricek J, Barry CE 3rd. 2008. PA-824 kills nonreplicating Mycobacterium tuberculosis by intracellular NO release. Science 322:1392-1395.
33. Stover CK, Warrener P, VanDevanter DR, Sherman DR, Arain TM, Langhorne MH, Anderson SW, Towell JA, Yuan Y, McMurray DN, Kreiswirth BN, Barry CE, Baker WR. 2000. A small-molecule nitroimidazopyran drug candidate for the treatment of tuberculosis. Nature 405: 962-966.
34. Aly S, Wagner K, Keller C, Malm S, Malzan A, Brandau S, Bange FC, Ehlers S. 2006. Oxygen status of lung granulomas in Mycobacterium tuberculosis-infected mice. J. Pathol. 210:298-305.
35. Tsai MC, Chakravarty S, Zhu G, Xu J, Tanaka K, Koch C, Tufariello J, Flynn J, Chan J. 2006. Characterization of the tuberculous granuloma in murine and human lungs: cellular composition and relative tissue oxygen tension. Cell. Microbiol. 8:218-232.
36. Lenaerts AJ, Gruppo V, Marietta KS, Johnson CM, Driscoll DK, Tompkins NM, Rose JD, Reynolds RC, Orme IM. 2005. 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. 49:2294-2301.
37. Tyagi S, Nuermberger E, Yoshimatsu T, Williams K, Rosenthal I, Lounis N, Bishai W, Grosset J. 2005. Bactericidal activity of the nitroimidazopyran PA-824 in a murine model of tuberculosis. Antimicrob. Agents Chemother. 49:2289-2293.
38. Via LE, Lin PL, Ray SM, Carrillo J, Allen SS, Eum SY, Taylor K, Klein E, Manjunatha U, Gonzales J, Lee EG, Park SK, Raleigh JA, Cho SN, McMurray DN, Flynn JL, Barry CE 3rd. 2008. Tuberculous granulomas are hypoxic in guinea pigs, rabbits, and nonhuman primates. Infect. Immun. 76:2333-2340.
39. Roy CJ, Sivasubramani SK, Dutta NK, Mehra S, Golden NA, Killeen S, Talton JD, Hammoud BE, Didier PJ, Kaushal D. 2012. Aerosolized gentamicin reduces the burden of tuberculosis in a murine model. Antimicrob. Agents Chemother. 56:883-886.
40. Vandiviere HM, Loring WE, Melvin I, Willis S. 1956. The treated pulmonary lesion and its tubercle bacillus. II. The death and resurrection. Am. J. Med. Sci. 232:30-37.
41. Lenaerts AJ, Hoff D, Aly S, Ehlers S, Andries K, Cantarero L, Orme IM, Basaraba RJ. 2007. Location of persisting mycobacteria in a guinea pig model of tuberculosis revealed by r207910. Antimicrob. Agents Chemother. 51:3338-3345.
42. Dutta NK, Pinn ML, Zhao M, Rudek MA, Karakousis PC. 2013. Thioridazine lacks bactericidal activity in an animal model of extracellular tuberculosis. J. Antimicrob. Chemother. 68:1327-1330.
43. Dorman SE, Goldberg S, Stout JE, Muzanyi G, Johnson JL, Weiner M, Bozeman L, Heilig CM, Feng PJ, Moro R, Narita M, Nahid P, Ray S, Bates E, Haile B, Nuermberger EL, Vernon A, Schluger NW. 2012. Substitution of rifapentine for rifampin during intensive phase treatment of pulmonary tuberculosis: study 29 of the Tuberculosis Trials Consortium. J. Infect. Dis. 206:1030-1040.
44. Rosenthal IM, Tasneen R, Peloquin CA, Zhang M, Almeida D, Mdluli KE, Karakousis PC, Grosset JH, Nuermberger EL. 2012. Dose-ranging comparison of rifampin and rifapentine in two pathologically distinct murine models of tuberculosis. Antimicrob. Agents Chemother. 56:4331-4340.
45. Harper J, Skerry C, Davis SL, Tasneen R, Weir M, Kramnik I, Bishai WR, Pomper MG, Nuermberger EL, Jain SK. 2012. Mouse model of necrotic tuberculosis granulomas develops hypoxic lesions. J. Infect. Dis. 205:595-602.
46. El Sahly HM, Teeter LD, Jost KC Jr, Dunbar D, Lew J, Graviss EA. 2011. Incidence of moxifloxacin resistance in clinical Mycobacterium tuberculosis isolates in Houston, Texas. J. Clin. Microbiol. 49:2942-2945.
47. Yeager RL, Munroe WG, Dessau FI. 1952. Pyrazinamide (aldinamide) in the treatment of pulmonary tuberculosis. Am. Rev. Tuberc. 65:523-546.
48. Canetti G. 1965. Present aspects of bacterial resistance in tuberculosis. Am. Rev. Respir. Dis. 92:687-703.
49. Grimaldo ER, Tupasi TE, Rivera AB, Quelapio MI, Cardano RC, Derilo JO, Belen VA. 2001. Increased resistance to ciprofloxacin and ofloxacin in multidrug-resistant Mycobacterium tuberculosis isolates from patients seen at a tertiary hospital in the Philippines. Int. J. Tuberc. Lung Dis. 5:546-550.
50. Agrawal D, Udwadia ZF, Rodriguez C, Mehta A. 2009. Increasing incidence of fluoroquinolone-resistant Mycobacterium tuberculosis in Mumbai, India. Int. J. Tuberc. Lung Dis. 13:79-83.
51. Diacon AH, Pym A, Grobusch M, Patientia R, Rustomjee R, Page-Shipp L, Pistorius C, Krause R, Bogoshi M, Churchyard G, Venter A, Allen J, Palomino JC, De Marez T, van Heeswijk RP, Lounis N, Meyvisch P, Verbeeck J, Parys W, de Beule K, Andries K, McNeeley DF. 2009. The diarylquinoline TMC207 for multidrug-resistant tuberculosis. N. Engl. J. Med. 360:2397-2405.
52. Mphahlele M, Syre H, Valvatne H, Stavrum R, Mannsaker T, Muthivhi T, Weyer K, Fourie PB, Grewal HM. 2008. Pyrazinamide resistance among South African multidrug-resistant Mycobacterium tuberculosis isolates. J. Clin. Microbiol. 46:3459-3464.