Skip to main content

Advertisement

SpringerLink
Log in

Peak plasma rifampicin level in tuberculosis patients with slow culture conversion

  • Brief Report
  • Published:
European Journal of Clinical Microbiology & Infectious Diseases Aims and scope Submit manuscript

Abstract

The clinical utility of therapeutic drug monitoring in tuberculosis has not been adequately evaluated by controlled clinical trials. To examine the relationship between slow culture conversion and peak plasma rifampicin level (Cmax-rfm) in a case-control study, patients with persistence of positive sputum smear despite at least 8 weeks of directly observed treatment with standard pyrazinamide-containing regimens were enrolled prospectively in government chest clinics from 16 December 2005 to 15 November 2006. Patients with multidrug-resistant tuberculosis, human immunodeficiency virus infection, or poor treatment adherence were excluded. Cases referred to patients with persistence of positive culture whereas controls had negative culture despite positive smear. Blood was checked at 2 and 4 hours post-dosing to capture Cmax-rfm. A cohort of 88 patients was identified. After excluding 16 patients, there were 36 controls and 36 cases. None had symptoms of malabsorption. Cmax-rfm was below 6 mg/l among 47% of controls and 44% of cases. Univariate and multiple logistic regression analyses showed no significant association between slow culture conversion and Cmax-rfm after logarithmic transformation. Thus, there is probably no association between Cmax-rfm and slow culture conversion.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1

References

  1. Peloquin CA (2002) Therapeutic drug monitoring in the treatment of tuberculosis. Drugs 62:2169–2183

    Article  PubMed  CAS  Google Scholar 

  2. Heifets L (1988) Qualitative and quantitative drug-susceptibility tests in mycobacteriology. Am Rev Respir Dis 137:1217–1222

    PubMed  CAS  Google Scholar 

  3. Kimerling ME, Phillips P, Patterson P, Hall M, Robinson CA, Dunlap NE (1998) Low serum antimycobacterial drug levels in non-HIV-infected tuberculosis patients. Chest 113:1178–1183

    Article  PubMed  CAS  Google Scholar 

  4. Mehta JB, Shantaveerapa H, Byrd Jr. RP, Morton SE, Fountain F, Roy TM (2001) 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 120:1520–1524

    Article  PubMed  CAS  Google Scholar 

  5. Ray J, Gardiner I, Marriott D (2003) Managing antituberculosis drug therapy by therapeutic drug monitoring of rifampicin and isoniazid. Intern Med J 33:229–234

    Article  PubMed  CAS  Google Scholar 

  6. Tappero JW, Bradford WZ, Agerton TB, Hopewell P, Reingold AL, Lockman S, Oyewo A, Talbot EA, Kenyon TA, Moeti TL, Moffat HJ, Peloquin CA (2005) Serum concentrations of antimycobacterial drugs in patients with pulmonary tuberculosis in Botswana. Clin Infect Dis 41:461–469

    Article  PubMed  CAS  Google Scholar 

  7. Nijland HM, Ruslami R, Stalenhoef JE, Nelwan EJ, Alisjahbana B, Nelwan RH, van der Ven AJ, Danusantoso H, Aarnoutse RE, van Crevel R (2006) Exposure to rifampicin is strongly reduced in patients with tuberculosis and type 2 diabetes. Clin Infect Dis 43:848–854

    Article  PubMed  CAS  Google Scholar 

  8. Jayaram R, Gaonkar S, Kaur P, Suresh BL, Mahesh BN, Jayashree R, Nandi V, Bharat S, Shandil RK, Kantharaj E, Balasubramanian V (2003) Pharmacokinetics-pharmacodynamics of rifampin in an aerosol infection model of tuberculosis. Antimicrob Agents Chemother 47:2118–2124

    Article  PubMed  CAS  Google Scholar 

  9. Weiner M, Burman W, Vernon A, Benator D, Peloquin CA, Khan A, Weis S, King B, Shah N, Hodge T; Tuberculosis Trials Consortium (2003) Low isoniazid concentrations and outcome of tuberculosis treatment with once-weekly isoniazid and rifapentine. Am J Respir Crit Care Med 167:1341–1347

    Google Scholar 

  10. Chan C (1988) A systematic approach for the simultaneous assay of some anti-tuberculous drug in CSF and plasma by liquid chromatography. J Liq Chromatogr 11:1051–1073

    Article  CAS  Google Scholar 

  11. Kim TC, Blackman RS, Heatwole KM, Kim T, Rochester DF (1984) Acid fast bacilli in sputum smears of patients with pulmonary tuberculosis: prevalence and significance of negative smears pretreatment and positive smears post-treatment. Am Rev Respir Dis 129:264–268

    PubMed  CAS  Google Scholar 

  12. Benator D, Bhattacharya M, Bozeman L, Burman W, Cantazaro A, Chaisson R, Gordin F, Horsburgh CR, Horton J, Khan A, Lahart C, Metchock B, Pachucki C, Stanton L, Vernon A, Villarino ME, Wang YC, Weiner M, Weis S; Tuberculosis Trials Consortium (2002) Rifapentine and isoniazid once a week versus rifampicin and isoniazid twice a week for treatment of drug-susceptible pulmonary tuberculosis in HIV-negative patients: a randomized clinical trial. Lancet 360:528–534

    Google Scholar 

  13. Mitchison DA (1993) Assessment of new sterilizing drugs for treating pulmonary tuberculosis by culture at 2 months. Am Rev Respir Dis 147:1062–1063

    PubMed  CAS  Google Scholar 

  14. Al-Moamary MS, Black W, Bessuille E, Elwood RK, Vedal S (1999) The significance of the persistent presence of acid-fast bacilli in sputum smears in pulmonary tuberculosis. Chest 116:726–731

    Article  PubMed  CAS  Google Scholar 

  15. Chang KC, Leung CC, Yew WW, Ho SC, Tam CM (2004) A nested case-control study on treatment-related risk factors for early relapse of tuberculosis. Am J Respir Crit Care Med 170:1124–1130

    Article  PubMed  Google Scholar 

  16. Chang KC, Leung CC, Yew WW, Chan SL, Tam CM (2006) Dosing schedules of 6-month regimens and relapse for pulmonary tuberculosis. Am J Respir Crit Care Med 174:1153–1158

    Article  PubMed  Google Scholar 

  17. Acocella G (1978) Clinical pharmaocokinetics of rifampicin. Clin Pharmacokinet 3:108–127

    Article  PubMed  CAS  Google Scholar 

  18. Long MW, Snider Jr. DE, Farer LS (1979) US Public Health Service Cooperative trial of three rifampin-isoniazid regimens in treatment of pulmonary tuberculosis. Am Rev Respir Dis 119:879–894

    PubMed  CAS  Google Scholar 

  19. Donald PR, Sirgel FA, Botha FJ, Seifart HI, Parkin DP, Vandenplas ML, Van de Wal BW, Maritz JS, Mitchison DA (1997) The early bactericidal activity of isoniazid related to its dose size in pulmonary tuberculosis. Am J Respir Crit Care Med 156:895–900

    PubMed  CAS  Google Scholar 

  20. Burman WJ (2003) The hunt for the elusive surrogate marker of sterilizing activity in tuberculosis treatment. Am J Respir Crit Care Med 167:1299–1301

    Article  PubMed  Google Scholar 

  21. Kradolfer F (1968) Relationships between chemotherapeutic activity and blood concentration of rifampin in murine tuberculosis. Am Rev Respir Dis 98:104–106

    PubMed  CAS  Google Scholar 

Download references

Acknowledgements

The authors would like to thank all colleagues in the Hong Kong Tuberculosis and Chest Service for their invaluable assistance in enrolling the study cohort.

Author information

Authors and Affiliations

  1. Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Wanchai Chest Clinic, 1/F, Wanchai Polyclinic, 99, Kennedy Road, Wanchai, Hong Kong, China

    K.-C. Chang & C.-M. Tam

  2. Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Pneumoconiosis Clinic, 4/F, Shaukeiwan Polyclinic, 8, Chai Wan Road, Hong Kong, China

    C.-C. Leung & W.-S. Law

  3. Tuberculosis and Chest Unit, Hospital Authority, Grantham Hospital, 125, Wong Chuk Hang Road, Aberdeen, Hong Kong, China

    W.-W. Yew

  4. Public Health Laboratory Centre, Centre for Health Protection, Department of Health, Tuberculosis Referance Laboratory, 382, Nam Cheong Street, Shek Kip Mei, Kowloon, Hong Kong, China

    K.-M. Kam, C.-W. Yip & C.-H. Ma

  5. Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Yan Oi Chest Clinic, 2/F, Yan Oi Polyclinic, 6 Tuen Lee Street, Tuen Mun, New Territories, Hong Kong, China

    E. C.-C. Leung

  6. Tuberculosis and Chest Service, Centre for Health Protection, Department of Health, Yaumatei Chest Clinic, 2/F, Yaumatei Jockey Club Polyclinic, 145, Battery Street, Kowloon, Hong Kong, China

    W.-M. Leung

Authors
  1. K.-C. Chang
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. C.-C. Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  3. W.-W. Yew
    View author publications

    You can also search for this author in PubMed Google Scholar

  4. K.-M. Kam
    View author publications

    You can also search for this author in PubMed Google Scholar

  5. C.-W. Yip
    View author publications

    You can also search for this author in PubMed Google Scholar

  6. C.-H. Ma
    View author publications

    You can also search for this author in PubMed Google Scholar

  7. C.-M. Tam
    View author publications

    You can also search for this author in PubMed Google Scholar

  8. E. C.-C. Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

  9. W.-S. Law
    View author publications

    You can also search for this author in PubMed Google Scholar

  10. W.-M. Leung
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to K.-C. Chang.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Chang, KC., Leung, CC., Yew, WW. et al. Peak plasma rifampicin level in tuberculosis patients with slow culture conversion. Eur J Clin Microbiol Infect Dis 27, 467–472 (2008). https://doi.org/10.1007/s10096-007-0454-6

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s10096-007-0454-6

Keywords

Search

Navigation