Journal List > Tuberc Respir Dis > v.66(3) > 1001347

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Jeon, Kim, Kang, Min, Sung, Hwang, and Park: Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis
Original Article
Tuberculosis and Respiratory Diseases

Tuberculosis and Respiratory Diseases 2009; 66(3): 198-204.

Published online: 31 March 2009

DOI: https://doi.org/10.4046/trd.2009.66.3.198

Acquired Drug Resistance during Standardized Treatment with First-line Drugs in Patients with Multidrug-Resistant Tuberculosis

Doosoo Jeon, M.D.1, 2, Dohyung Kim, M.D.1, Hyungseok Kang, M.D.1, Jinhong Min, M.D.1, Nackmoon Sung, Ph.D.1, Soohee Hwang, M.D.1, Seungkew Park, M.D., Ph.D.1, 2

1National Masan Tuberculosis Hospital, Masan, Korea.

2International Tuberculosis Research Center, Masan, Korea.

Address for correspondence: Doosoo Jeon, M.D. National Masan Tuberculosis Hospital, 486, Gapo-dong, Masan 631-710, Korea. Phone: 82-55-249-3786, Fax: 82-55-246-1162, sooli10kr@yahoo.co.kr

Received 2 February 2009       Accepted 9 March 2009

Copyright©2009. The Korean Academy of Tuberculosis and Respiratory Diseases. All rights reserved.

Abstract

Background

First-line drugs, if sensitive, are the most potent drugs in the treatment of multidrug-resistant tuberculosis (MDR-TB). This study examined the frequency and risk factors associated with acquired drug resistance to first-line drugs during a standardized treatment using first-line drugs in patients with MDR-TB.

Methods

This study included patients who were diagnosed with MDR-TB at the National Masan Tuberculosis Hospital between January 2004 and May 2008, treated with standardized first-line drugs, and for whom the preand post-treatment results of the drug susceptibility test were available. Their medical records were reviewed retrospectively.

Results

Of 41 MDR-TB patients, 14 (34.1%) acquired additional resistance to ethambutol (EMB) or pyrazinamide (PZA). Of 11 patients initially resistant to isoniazid (INH) and rifampicin (RFP), 3 (27.3%) acquired additional resistance to both EMB and PZA, and 3 (27.3%) to PZA. Of 18 patients initially resistant to INH, RFP and EMB, 6 (33.3%) acquired additional resistance to PZA. Of 6 patients initially resistant to INH, RFP and PZA, 2 (33.3%) acquired additional resistance to EMB. Ten of the 41 MDR-TB patients (24.4%) changed from resistant to susceptible. No statistically significant risk factors associated with acquired resistance could be found.

Conclusion

First-line drugs should be used cautiously in the treatment of MDR-TB in Korea considering the potential acquisition of drug resistance.

Keywords: Tuberculosis, Multidrug resistance, Drug resistance

Figures and Tables

Table 1
Laboratory institutes of drug susceptibility test
trd-66-198-i001

NMTH: national masan tuberculosis hospital; KIT: Korean institute of tuberculosis; GCRL: green cross reference laboratory; SCL: seoul clinical laboratory; H: isoniazid; R: rifampicin; E: ethambutol; Z: pyrazinamide; PZAse: pyrazinamidase.

Table 2
Baseline characteristics of 41 patients with multidrug-resistant tuberculosis
trd-66-198-i002

H: isoniazid; R: rifampicin; E: ethambutol; Z: pyrazinamide.

Table 3
Frequency of acquired drug resistance during treatment with first-line drugs
trd-66-198-i003

DST: drug susceptibility test; Re: resistance; H: isoniazid; R: rifampicin; E: ethambutol; Z: pyrazinamide.

*Duration of treatment until the date of sputum collection for post-treatment drug susceptibility test.

Table 4
Univariate analysis of risk factors associated with acquired drug resistance during treatment with first-line drugs
trd-66-198-i004

H: isoniazid; R: rifampicin; E: ethambutol; Z: pyrazinamide.

References

1. Kim HJ, Hong YP, Kim SJ, Lew WJ, Lee EG. Ambulatory treatment of multidrug-resistant pulmonary tuberculosis patients at a chest clinic. Int J Tuberc Lung Dis. 2001. 5:1129–1136.
2. Park SK, Lee WC, Lee DH, Mitnick CD, Han L, Seung KJ. Self-administered, standardized regimens for multidrug-resistant tuberculosis in South Korea. Int J Tuberc Lung Dis. 2004. 8:361–368.
3. Kim HR, Hwang SS, Kim HJ, Lee SM, Yoo CG, Kim YW, et al. Impact of extensive drug resistance on treatment outcomes in non-HIV-infected patients with multidrug-resistant tuberculosis. Clin Infect Dis. 2007. 45:1290–1295.
4. Kwon YS, Kim YH, Suh GY, Chung MP, Kim H, Kwon OJ, et al. Treatment outcomes for HIV-uninfected patients with multidrug-resistant and extensively drug-resistant tuberculosis. Clin Infect Dis. 2008. 47:496–502.
5. Kim DH, Kim HJ, Park SK, Kong SJ, Kim YS, Kim TH, et al. Treatment outcomes and long-term survival in patients with extensively drug-resistant tuberculosis. Am J Respir Crit Care Med. 2008. 178:1075–1082.
6. Mukherjee JS, Rich ML, Socci AR, Joseph JK, Virú FA, Shin SS, et al. Programmes and principles in treatment of multidrug-resistant tuberculosis. Lancet. 2004. 363:474–481.
7. World Health Organization. Guidelines for the programmatic management of drug-resistant tuberculosis: emergency update 2008. 2008. Geneva: World Health Organization.
8. Migliori GB, Besozzi G, Girardi E, Kliiman K, Lange C, Toungoussova OS, et al. Clinical and operational value of the extensively drug-resistant tuberculosis definition. Eur Respir J. 2007. 30:623–626.
9. Joh JS, Lee CH, Lee JE, Park YK, Bai GH, Kim EC, et al. The interval between initiation of anti-tuberculosis treatment in patients with culture-positive pulmonary tuberculosis and receipt of drug-susceptibility test results. J Korean Med Sci. 2007. 22:26–29.
10. Kim MN, Lee SH, Yang SE, Pai CH. Mycobacterial testing in hospital laboratories in Korea: results of a survey of 40 university or tertiary-care hospitals. Korean J Clin Pathol. 1999. 19:86–91.
11. National Tuberculosis Association. Diagnostic standards and classification of tuberculosis. 1961. 11th ed. New York: National Tuberculosis Assoication.
12. American Thoracic Society. Centers for Disease Control and Prevention. Infectious Diseases Society of America. American Thoracic Society/Centers for Disease Control and Prevention/Infectious Diseases Society of America: controlling tuberculosis in the United States. Am J Respir Crit Care Med. 2005. 172:1169–1227.
13. Mitchison DA. How drug resistance emerges as a result of poor compliance during short course chemotherapy for tuberculosis. Int J Tuberc Lung Dis. 1998. 2:10–15.
14. Farmer P, Bayona J, Becerra M, Furin J, Henry C, Hiatt H, et al. The dilemma of MDR-TB in the global era. Int J Tuberc Lung Dis. 1998. 2:869–876.
15. Umubyeyi A, Shamputa IC, Rigouts L, Dediste A, Struelens M, Portaels F. Evidence of 'amplifier effect' in pulmonary multidrug-resistant tuberculosis: report of three cases. Int J Infect Dis. 2007. 11:508–512.
16. Quy HT, Lan NT, Borgdorff MW, Grosset J, Linh PD, Tung LB, et al. Drug resistance among failure and relapse cases of tuberculosis: is the standard re-treatment regimen adequate? Int J Tuberc Lung Dis. 2003. 7:631–636.
17. Yoshiyama T, Yanai H, Rhiengtong D, Palittapongarnpim P, Nampaisan O, Supawitkul S, et al. Development of acquired drug resistance in recurrent tuberculosis patients with various previous treatment outcomes. Int J Tuberc Lung Dis. 2004. 8:31–38.
18. Temple B, Ayakaka I, Ogwang S, Nabanjja H, Kayes S, Nakubulwa S, et al. Rate and amplification of drug resistance among previously-treated patients with tuberculosis in Kampala, Uganda. Clin Infect Dis. 2008. 47:1126–1134.
19. Seung KJ, Gelmanova IE, Peremitin GG, Golubchikova VT, Pavlova VE, Sirotkina OB, et al. The effect of initial drug resistance on treatment response and acquired drug resistance during standardized short-course chemotherapy for tuberculosis. Clin Infect Dis. 2004. 39:1321–1328.
20. Han LL, Sloutsky A, Canales R, Naroditskaya V, Shin SS, Seung KJ, et al. Acquisition of drug resistance in multidrug-resistant Mycobacterium tuberculosis during directly observed empiric retreatment with standardized regimens. Int J Tuberc Lung Dis. 2005. 9:818–821.
21. Cox HS, Niemann S, Ismailov G, Doshetov D, Orozco JD, Blok L, et al. Risk of acquired drug resistance during short-course directly observed treatment of tuberculosis in an area with high levels of drug resistance. Clin Infect Dis. 2007. 44:1421–1427.
22. Tenover FC, Crawford JT, Huebner RE, Geiter LJ, Horsburgh CR Jr, Good RC. The resurgence of tuberculosis: is your laboratory ready? J Clin Microbiol. 1993. 31:767–770.
23. Oh SH, Kim YJ, Park SK, Hwang SH, Kim HH, Lee EY, et al. Comparison of anti-mycobacterial drug susceptibility test results by institutes and methods. Korean J Clin Microbiol. 2008. 11:43–48.
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