OJMM  Vol.5 No.2 , June 2015
Low Doses of Rifampicin Used in New Tuberculosis Patients Correlated to Increased Frequency of Rifampicin-Resistance and Poorer Treatment Outcomes
ABSTRACT
The prognosis of patients with previously treated tuberculosis (TB) was suggested to be dependent on whether the initial treatment was in compliance with the established guidelines. The aim of this retrospective multicenter study was to determine the proportion of new TB patients who received standard doses of rifampicin in multiple provinces of China, and the relationship between low doses of rifampicin and frequency of rifampicin-resistance as well as treatment outcomes. A total of 713 new TB patients were treated with either once-daily dose of bulk anti-TB drugs (group I) or every other day combination blister packs of anti-TB drugs containing rifampicin (group II) at more than 30 TB treatment centers/hospitals in China. Treatment history, therapeutic doses of rifampicin, and information about patients were extracted from their medical records and analyzed, and rifampicin-resistance of isolates collected from patients following the treatment as well as treatment outcomes were compared between two treatment groups. Among 522 patients in treatment group I, 154 (29.5%) received standard and 363 (69.5%) received low doses of rifampicin; 238 (45.6%) isolates were rifampicin-resistant, and 243 (46.6%) were successfully treated. Among 191 patients in treatment group II, 175 (91.6%) received standard and 15 (7.9%) received low doses of rifampicin; 72 (37.7%) isolates were rifampicin-resistant, and 105 (55%) were successfully treated. When patients who received low doses of rifampicin were compared to others within the same treatment group, increased rates for rifampicin-resistance and treatment failure were observed. Results from this study showed that most new TB patients in treatment group I (69.5%) received low doses of rifampicin, and their treatment outcomes were worse than those in treatment group II, indicating that low doses of rifampicin used for the initial treatment of new TB patients were correlated to increased frequency of rifampicin-resistance and poorer treatment outcomes.

Cite this paper
Chen, L. , Du, J. , Li, L. , Li, Q. , Zhong, Q. , Fu, Y. , Li, B. , Lin, M. , Ma, L. , Li, Y. , Wang, X. , Ma, Y. , Jiang, X. , Chen, X. , Ge, Q. , Xie, L. , Han, X. , Sun, Z. , Jiang, G. , Zhang, H. and Gao, W. (2015) Low Doses of Rifampicin Used in New Tuberculosis Patients Correlated to Increased Frequency of Rifampicin-Resistance and Poorer Treatment Outcomes. Open Journal of Medical Microbiology, 5, 76-84. doi: 10.4236/ojmm.2015.52009.
References
[1]   World Health Organization. (2014) Global Tuberculosis Report 2014.
http://www.who.int/tb/publications/global_report/en/

[2]   World Health Organization. (2010) Guidelines for Treatment of Tuberculosis. 4th Edition.
http://www.who.int/tb/publications/2010/9789241547833/en/

[3]   Centers for Disease Control and Prevention. Tuberculosis (TB) Treatment.
http://www.cdc.gov/tb/topic/treatment/default.htm

[4]   Xiao, D.L., Zhao, M.G. and Wang, Y. (2008) Implementation Guidelines for Chinese Tuberculosis Control Programs. Peking Union Medical College Press, Beijing.

[5]   Chinese Medical Association. (2005) Guidelines for Clinical Diagnosis and Treatment of Tuberculosis. People’s Health Press, Beijing.

[6]   Norval, P.Y. (2010) Review of Prescribing Practices: An Essential Tool for Measuring the Quality of Tuberculosis Services. International Journal of Tuberculosis and Lung Diseases, 14, 795.

[7]   Curry International TB Center and California Department of Public Health. (2011) Drug-Resistant Tuberculosis: A Survival Guide for Clinicians. 2nd Edition.
http://www.currytbcenter.ucsf.edu/drtb/docs/MDRTB_book_2011.pdf

[8]   Nijland, H.M., Ruslami, R., Stalenhoef, J.E., Nelwan, E.J., Alisjahbana, B., Nelwan, R.H., van der Ven, A.J., Danusantoso, H., Aarnoutse, R.E. and van Crevel, R. (2006) Exposure to Rifampicin Is Strongly Reduced in Patients with Tuberculosis and Type 2 Diabetes. Clinical Infectious Diseases, 43, 848-854.
http://dx.doi.org/10.1086/507543

[9]   Ruslami, R., Nijland, H.M., Adhiarta, I.G., Kariadi, S.H., Alisjahbana, B., Aarnoutse, R.E. and van Crevel, R. (2010) Pharmacokinetics of Antituberculosis Drugs in Pulmonary Tuberculosis Patients with Type 2 Diabetes. Antimicrobial Agents and Chemotherapy, 54, 1068-1074.
http://dx.doi.org/10.1128/AAC.00447-09

[10]   Ruslami, R., Nijland, H., Aarnoutse, R., Alisjahbana, B., Soeroto, A.Y., Ewalds, S. and van Crevel, R. (2006) Evaluation of High-Versus Standard-Dose Rifampin in Indonesian Patients with Pulmonary Tuberculosis. Antimicrobial Agents and Chemotherapy, 50, 822-823.
http://dx.doi.org/10.1128/AAC.50.2.822-823.2006

[11]   Hao, L.H., Guo, S.C., Liu, C.C., Zhu, H., Wang, B., Fu, L., Chen, M.T., Zhou, L., Chi, J.Y., Yang, W., Nie, W.J. and Lu, Y. (2014) Comparative Bioavailability of Rifampicin and Isoniazid in Fixed-Dose Combinations and Single-Drug Formulations. International Journal of Tuberculosis and Lung Diseases, 18, 1505-1512.
http://dx.doi.org/10.5588/ijtld.13.0647

[12]   Zhu, H., Guo, S.C., Hao, L.H., Liu, C.C., Wang, B., Fu, L., Chen, M.T., Zhou, L., Chi, J.Y., Yang, W., Nie, W.J. and Lu, Y. (2015) Relative Bioavailability of Rifampicin in Four Chinese Fixed-Dose Combinations Compared with Rifampicin in Free Combinations. Chinese Medical Journal (English), 128,433-437.

[13]   Zhang, Z., Dai, F., Luo, F., Zhong, M., Huang, Z., Hou, T. and Xu, J. (2014) Could High-Concentration Rifampicin Kill Rifampicin-Resistant M. Tuberculosis? Rifampicin MIC Test in Rifampicin-Resistant Isolates from Patients with Osteoarticular Tuberculosis. Journal of Orthopaedic Surgery and Research, 9, 124.
http://dx.doi.org/10.1186/s13018-014-0124-1

[14]   Technical Guidance Group of the Fifth National TB Epidemiological Survey, Office of the Fifth National TB Epidemiological Survey (2012) 2010 National Tuberculosis Epidemiological Survey in China. Chinese Journal of Antituberculosis, 34, 485-508.

[15]   Phanouvong, S., Vrakking, H., Blanc, L., Wondemagegnehu, E., Moore, T., Rägo, L., Mboussa, J., Norval, P. and Matji, R. (2002) Operational Guide for National Tuberculosis Control Programmes on the Introduction and Use of Fixed-Dose Combination Drugs.
http://whqlibdoc.who.int/hq/2002/WHO_CDS_TB_2002.308.pdf

[16]   Xie, L., Gao, W.W., Bu, J.L. and Ma, Y. (2008) Analysis of 702 Cases of Adverse Drug Reactions Due to Anti-Tuberculosis Drugs. Chinese Journal of Antituberculosis, 30, 275-278.

[17]   Xia, Y.Y. and Zhan, S.Y. (2007) Systematic Review of Anti-Tuberculosis Drug Induced Adverse Reactions in China. Chinese Journal of Tuberculosis and Respiratory Diseases, 30, 419-423.

[18]   Chiang, C.Y., Bai, K.J., Lee, C.N., Enarson, D.A., Suo, J. and Luh, K.T. (2010) Inconsistent Dosing of Anti-Tuberculosis Drugs in Taipei, Taiwan. International Journal of Tuberculosis and Lung Diseases, 14, 878-883.

[19]   Zhang, D.R. (1995) New Concepts of Tuberculosis. Chinese Agricultural Science and Technology Press, Beijing.

[20]   Tu, D.H. and Wan, L.Y. (2009) Modern Theories and Practices for Tuberculosis Control. Modern Education Press, Beijing.

[21]   Shang, P., Xia, Y., Liu, F., Wang, X., Yuan, Y., Hu, D., Tu, D., Chen, Y., Deng, P., Cheng, S., Zhou, L., Ma, Y., Zhu, L., Gao, W., Wang, H., Chen, D., Yang, L., He, P., Wu, S., Tang, S., Lv, X., Shu, Z., Zhang, Y., Yang, Z., Chen, Y., Li, N., Sun, F., Li, X., He, Y., Garner, P. and Zhan, S. (2011) Incidence, Clinical Features and Impact on Anti-Tuberculosis Treatment of Anti-Tuberculosis Drug Induced Liver Injury (ATLI) in China. PLoS ONE, 6, e21836.
http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0021836
http://dx.doi.org/10.1371/journal.pone.0021836


[22]   de Steenwinkel, J.E., Aarnoutse, R.E., de Knegt, G.J., ten Kate, M.T., Teulen, M., Verbrugh, H.A., Boeree, M.J., van Soolingen, D. and Bakker-Woudenberg, I.A. (2013) Optimization of the Rifampin Dosage to Improve the Therapeutic Efficacy in Tuberculosis Treatment Using a Murine Model. American Journal of Respiratory and Critical Care Medicine, 187, 1127-1134.
http://dx.doi.org/10.1164/rccm.201207-1210OC

 
 
Top