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Volume 16, Number 10—October 2010
Research

Therapeutic Drug Monitoring for Slow Response to Tuberculosis Treatment in a State Control Program, Virginia, USA

Scott K. HeysellComments to Author , Jane L. Moore, Suzanne J. Keller, and Eric R. Houpt
Author affiliations: Author affiliations: University of Virginia, Charlottesville, Virginia, USA (S.K. Heysell, E.R. Houpt); Virginia Department of Health, Richmond, Virginia, USA (J.L. Moore, S.J. Keller)

Main Article

Table 1

Baseline characteristics of adults treated for drug-susceptible pulmonary TB in a state control program, Virginia, USA, March 1, 2007–May 1, 2009*

Characteristic All patients, N = 311, no. (%) Slow response,
n = 42, no. (%) Normal response,
n = 269, no. (%) Bivariate OR (95% CI);
p value
Age, y
18–39 151 (49) 16 (38) 135 (50) Referent
40–64 90 (29) 13 (31) 77 (29) 1.4 (0.65–3.10); p = 0.38
>65
 70 (22)
 13 (31)
 57 (21)
 1.9 (0.87–4.30); p = 0.11
Sex
M 204 (65) 29 (69) 175 (65) Referent
F
 107 (35)
 13 (31)
 94 (35)
 0.84 (0.42–1.70); p = 0.61
Race/ethnicity
Asian 102 (33) 19 (45) 83 (31) Referent
Hispanic 82 (26) 11 (26) 71 (26) 0.67 (0.30–1.50); p = 0.34
Black 86 (28) 8 (19) 78 (29) 0.45 (0.19–1.10); p = 0.07
White 41 (13) 4 (10) 37 (14) 0.47 (0.15–1.50); p = 0.20
Native American
 0
 0
 0
Foreign born
No 83 (27) 9 (21) 74 (28) Referent
Yes
 228 (73)
 33 (79)
 195 (72)
 1.4 (0.64–3.00); p = 0.41
Homeless
No 301 (97) 41 (98) 260 (97) Referent
Yes
 10 (3)
 1 (2)
 9 (3)
 0.71 (0.09–5.70); p = 0.74
Illicit drug use
No 298 (96) 42 (100) 256 (95) Referent
Non-injection use 7 (2) 0 7 (3) p>0.99
Injection use
 6 (2)
 0
 6 (2)
 p>0.99
Alcohol abuse
No 276 (89) 38 (91) 238 (89) Referent
Yes
 35 (11)
 4 (9)
 31 (11)
 0.81 (0.27–2.40); p = 0.70
HIV status
Negative 266 (86) 37 (88) 229 (85) Referent
Positive 11 (3) 0 11 (4) p>0.99
Unknown
 34 (11)
 5 (12)
 29 (11)
 1.1 (0.39–2.90); p = 0.90
Diabetes
No 270 (87) 25 (60) 245 (91) Referent
Yes
 41 (13)
 17 (40)
 24 (9)
 6.9 (3.3–14.6); p<0.001†
Prior TB history
No 291 (93) 38 (91) 253 (94) Referent
Yes 18 (6) 3 (7) 15 (5) 1.3 (0.37–4.80); p = 0.66
Unknown
 2 (1)
 1 (2)
 1 (1)
 6.6 (0.41–108.70); p = 0.18
Tuberculin skin test result
Negative 47 (15) 5 (12) 42 (16) Referent
Positive 179 (58) 23 (55) 156 (58) 1.2 (0.44–3.50); p = 0.68
Unavailable
 85 (27)
 14 (33)
 71 (26)
 1.7 (0.56–4.90); p = 0.36
Sputum smear
Negative 94 (30) 9 (21) 85 (31) Referent
Positive 193 (62) 30 (72) 163 (61) 1.7 (0.79–3.80); p = 0.17
Not done
 24 (8)
 3 (7)
 21 (8)
 1.3 (0.34–5.40); p = 0.67
Chest radiograph
No TB findings 16 (5) 2 (5) 14 (5) Referent
Noncavitary 173 (56) 19 (45) 154 (57) 0.86 (0.18–4.10); p = 0.85
Cavitary
 122 (39)
 21 (50)
 101 (38)
 1.5 (0.31–6.80); p = 0.64
Disease site
Pulmonary 212 (68) 32 (76) 180 (67) Referent
Pulmonary/extrapulmonary 99 (32) 10 (24) 89 (33) 0.63 (0.30–1.30); p = 0.23

*Tuberculin skin test values recorded in surveillance database as positive based on guidelines from the American Thoracic Society and Centers for Disease Control and Prevention (15). TB, tuberculosis; OR, odds ratio; CI, confidence interval.
†Adjusted odds ratio 6.3 (95% CI 2.8–14.0); p<0.001.

Main Article

References
  1. World Health Organization. Global tuberculosis control: a short update to the 2009 report. 2009 [cited 2010 July 21]. http://www.who.int/tb/publications/global_report/2009/update/en/index.html
  2. American Thoracic Society, Centers for Disease Control and Prevention, and Infectious Disease Society of America. Treatment of tuberculosis. MMWR Recomm Rep. 2003;52:1203.
  3. Peloquin  CA. Pharmacological issues in the treatment of tuberculosis. Ann N Y Acad Sci. 2001;953:157–64. DOIPubMedGoogle Scholar
  4. Peloquin  CA. Therapeutic drug monitoring in the treatment of tuberculosis. Drugs. 2002;62:2169–83. DOIPubMedGoogle Scholar
  5. Blumberg  HM, Burman  WJ, Chaisson  RE, Daley  CL, Etkind  SC, Friedman  LN, American Thoracic Society/Centers for Disease Control and Prevention/ Infectious Diseases Society of America: treatment of tuberculosis. Am J Respir Crit Care Med. 2003;167:603–62. DOIPubMedGoogle Scholar
  6. Kimerling  ME, Phillips  P, Patterson  P, Hall  M, Robinson  A, Dunlop  NE. Low serum antimycobacterial drug levels in non-HIV–infected tuberculosis patients. Chest. 1998;113:1178–83. DOIPubMedGoogle Scholar
  7. Mehta  JB, Shantaveerapa  H, Byrd  RP, Morton  SE, Fountain  F, Roy  TM. Utility of rifampin blood levels in the treatment and follow-up of active pulmonary tuberculosis in patients who were slow to respond to routine directly observed therapy. Chest. 2001;120:1520–4. DOIPubMedGoogle Scholar
  8. Narita  M, Hisada  M, Thimmappa  B, Stambaugh  JJ, Ibrahim  E, Hollender  ES, Tuberculosis recurrence: multivariate analysis of serum levels of tuberculosis drugs, HIV status, and other risk factors. Clin Infect Dis. 2001;32:515–7. DOIPubMedGoogle Scholar
  9. McIlleron  H, Wash  P, Burger  A, Norman  J, Folb  PI, Smith  P. Determinants of rifampin, isoniazid, pyrazinamide and ethambutol pharmacokinetics in a cohort of tuberculosis patients. Antimicrob Agents Chemother. 2006;50:1170–7. DOIPubMedGoogle Scholar
  10. Holland  DP, Hamilton  CD, Weintrob  AC, Engemann  JJ, Fortenberry  ER, Peloquin  CA, Therapeutic drug monitoring of antimycobacterial drugs in patients with both tuberculosis and advanced human immunodeficiency virus infection. Pharmacotherapy. 2009;29:503–10. DOIPubMedGoogle Scholar
  11. Patel  KB, Belmonte  R, Crowe  HM. Drug malabsorption and resistant tuberculosis in HIV-infected patients. N Engl J Med. 1995;332:336–7. DOIPubMedGoogle Scholar
  12. Peloquin  CA, Nitta  AT, Burman  WJ, Brudney  KF, Miranda-Massari  JR, McGuinness  ME, Low antituberculosis drug concentrations in patients with AIDS. Ann Pharmacother. 1996;30:919–25.PubMedGoogle Scholar
  13. Chideya  S, Winston  CA, Peloquin  CA, Bradford  WZ, Hopewell  PC, Wells  CD, Isoniazid, rifampin, ethambutol and pyrazinamide pharmacokinetics and treatment outcomes among predominately HIV-infected cohort of adults with tuberculosis from Botswana. Clin Infect Dis. 2009;48:1685–94. DOIPubMedGoogle Scholar
  14. Chang  KC, Leung  CC, Yew  WW, Kam  KM, Yip  CW, Ma  CH, Peak plasma rifampicin level in tuberculosis patients with slow culture conversion. Eur J Clin Microbiol Infect Dis. 2008;27:467–72. DOIPubMedGoogle Scholar
  15. American Thoracic Society and the Centers for Disease Control and Prevention. Diagnostic standards and classification of tuberculosis in adults and children. Am J Respir Crit Care Med. 2000;161:1376–95.PubMedGoogle Scholar
  16. Sirgel  FA, Fourie  PB, Donald  PR, Padayatchi  N, Rostomjee  R, Levin  J, The early bactericidal activities of rifampin and rifapentine in pulmonary tuberculosis. Am J Respir Crit Care Med. 2005;172:128–35. DOIPubMedGoogle Scholar
  17. Diacon  AH, Patientia  R, Venter  A, van Helden  PD, Smith  PJ, McIlleron  H, Early bactericidal activity of high-dose rifampin in patients with pulmonary tuberculosis evidenced by positive sputum smears. Antimicrob Agents Chemother. 2007;51:2994–6. DOIPubMedGoogle Scholar
  18. Gelband  H. Regimens of less than six months for treating tuberculosis. Cochrane Database Syst Rev. 2000; (2):CD001362.PubMedGoogle Scholar
  19. Davies  GR, Neurmberger  EL. Pharmokinetics and pharmacodynamics in the development of anti-tuberculosis drugs. Tuberculosis (Edinb). 2008;88:S65–74. DOIPubMedGoogle Scholar
  20. Peloquin  C. What is the right dose of rifampin? Int J Tuberc Lung Dis. 2003;7:3–5.PubMedGoogle Scholar
  21. Jeon  CY, Murray  MB. Diabetes mellitus increases the risk of active tuberculosis: a systematic review of 13 observational studies. PLoS Med. 2008;5:e152. DOIPubMedGoogle Scholar
  22. Stevenson  CR, Forouhi  NG, Roglic  G, Williams  BG, Lauer  JA, Dye  C, Diabetes and tuberculosis: the impact of the diabetes epidemic on tuberculosis incidence. BMC Public Health. 2007;7:234. DOIPubMedGoogle Scholar
  23. Alisjahbana  B, Sahiratmadja  E, Nelwan  EJ, Purwa  AM, Ahmad  Y, Ottenhoff  THM, The effect of type 2 diabetes on presentation and treatment response in tuberculosis. Clin Infect Dis. 2007;45:428–35. DOIPubMedGoogle Scholar
  24. Dooley  KE, Tang  T, Golub  JE, Dorman  SE, Cronin  W. Impact of diabetes mellitus on treatment outcomes of patients with active tuberculosis. Am J Trop Med Hyg. 2009;80:634–9.PubMedGoogle Scholar
  25. Gwilt  PR, Nahhas  RR, Tracewell  WG. The effects of diabetes mellitus on pharmacokinetics and pharmacodynamics in humans. Clin Pharmacokinet. 1991;20:477–90. DOIPubMedGoogle Scholar
  26. Nijland  HMJ, Ruslami  R, Stalenhoef  JE, Nelwan  EJ, Alisjahbana  B, Nelwan  RHH, Exposure to rifampin is strongly reduced in patients with tuberculosis and type 2 diabetes. Clin Infect Dis. 2006;43:848–54. DOIPubMedGoogle Scholar
  27. Kenny  MT, Strates  B. Metabolism and pharmacokinetics of the antibiotic rifampin. Drug Metab Rev. 1981;12:159–218. DOIPubMedGoogle Scholar
  28. Panchagnula  R, Agrawal  S, Ashokraj  Y. Fixed dose combinations for tuberculosis: lessons learned from clinical, formulation and regulatory perspective. Methods Find Exp Clin Pharmacol. 2004;26:703–21. DOIPubMedGoogle Scholar
  29. Malone  RS, Fish  DN, Spiegel  DM, Childs  JM, Peloquin  CA. The effect of hemodialysis on isoniazid, rifampin, pyrazinamide, and ethambutol. Am J Respir Crit Care Med. 1999;159:1580–4.PubMedGoogle Scholar
  30. Holdiness  MR. Clinical pharmacokinetics of the antituberculosis drugs. Clin Pharmacokinet. 1984;9:511–44. DOIPubMedGoogle Scholar

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Page updated: September 07, 2011
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