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Vol. 12, No. 5
May 2006

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Etymology

Letter

Drug-resistant Mycobacterium tuberculosis, Taiwan

Ruwen Jou,*Comments Pei-Chun Chuang,* Ying-Shun Wu,† Jing-Jou Yan,‡ and Kwen-Tay Luh§
Center for Disease Control, Taipei, Taiwan, Republic of China; †Chest Hospital, Tainan, Taiwan, Republic of China; ‡National Cheng Kung University Hospital, Tainan, Taiwan, Republic of China; and §National Association of Tuberculosis, Taipei, Taiwan, Republic of China

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To the Editor: Global surveillance of drug resistance has shown that a substantial proportion of tuberculosis (TB) patients are infected with drug-resistant Mycobacterium tuberculosis strains (1). Earlier hospital-based surveys have been undertaken in Taiwan, but these lacked systematic sampling and testing methods, which made interpreting results difficult. The combined treatment efficiency and the actual prevalence of drug resistance were unknown. Thus the Taiwan Center for Disease Control initiated the Taiwan Surveillance of Drug Resistance in Tuberculosis program in 2002.

A laboratory surveillance system was established and supervised by the national reference laboratory. The system includes 6 medical centers, 2 TB referral centers, and 1 regional hospital, distributed in 4 regions of Taiwan. The 9 laboratories provide services for healthcare facilities in their own and surrounding areas. Both the national reference laboratory and contract laboratories participated in an external quality proficiency test provided by the College of American Pathologists and the national reference laboratory. Performance was also assessed by the supranational reference laboratory in Antwerp, Belgium.

The population in the first year (2003) of the survey was 22,562,663, the number of confirmed TB cases was 15,042, the estimated incidence was 66.7 per 100,000 population, and the rate of notification of new positive sputum samples was 34.6% (2). A total of 3,699 isolates, ≈50% of M. tuberculosis strains isolated, underwent antimicrobial drug susceptibility testing in the system. Since clinical data were not available, only combined (primary plus acquired) drug resistance rates were analyzed. The survey showed that the combined drug resistance rates were 9.5% to isoniazid, 5.8% to ethambutol, 6.4% to rifampin, 9.6% to streptomycin, 20.0% to any drug, and 4.0% to multiple drugs. Resistance to any single drug was 12.3%, to any 2 drugs was 4.8%, to any 3 drugs was 2.2%, and to any 4 drugs was 0.7%. In the third global drug resistance surveillance report, the median prevalence of combined drug resistance was 6.6% to isoniazid, 1.3% to ethambutol, 2.2% to rifampin, 6.1% to streptomycin, 10.4% to any drug, and 1.7% to multiple drugs (1).

Available historical data from Taiwan are not directly comparable because of different sampling methods and because susceptibility testing methods have been applied in various hospital settings over time (Table), which limits our ability to monitor trends. The latest drug resistance rates obtained from Chest Hospital, a specialized TB referral hospital, showed that the combined drug resistance of any and multiple drugs were 27.6% and 15.8%, respectively, from January 2002 to June 2004 (unpub. data).

In Taiwan, isoniazid and rifampin were introduced in 1957 and 1978, respectively. Rifampin resistance was first seen in Taiwan in 1982. In recent decades, however, the rates of primary rifampin resistance have increased (Table), and primary resistance to multiple drugs has increased to 2.4% over time.

Based on patient data collected from Chest Hospital, multidrug resistance occurred in 42.2% of retreated TB patients, and 1.8% of multidrug-resistant isolates were found in new TB patients from January 2002 to June 2004 (unpub. data). In the third global drug resistance surveillance report, the median prevalence of multidrug resistance was 7.0% (highest 58.3%) among retreated cases and 1.1% (highest 14.2%) among new cases.

Significant declining trends were observed for any acquired resistance (67.0% to 42.6%, p<0.0001) and acquired multidrug resistance (46.0% to 24.6%, p<0.0001) at the Taiwan Provincial Chronic Disease Control Bureau from 1996 to 2001 (3,4). In addition, a decline in combined isoniazid resistance (43.1% to 16.4%, p < 0.0001), rifampin resistance (23.4% to 9.5%, p<0.0049), and multidrug resistance (18.2% to 7.8%, p<0.0113) was also reported from Kaohsiung Medical University Hospital from 1996 to 2000 (5). Taken together, data obtained from the Taiwan Surveillance of Drug Resistance in Tuberculosis and those reported previously show that rates of combined resistance to any drugs and multiple drugs has declined in Taiwan.

For retreated cases, the high acquired resistance rates indicated suboptimal initial treatment and insufficient case management of new patients, which raises a challenge to the National TB Control Programme in Taiwan. The direct observed treatment, short-course (DOTS) strategy has consequently been suggested to expand to all patients with newly diagnosed cases. The Taiwan Surveillance of Drug Resistance in Tuberculosis program will be extended to collect each patient's clinical and epidemiologic data, according to principles suggested in the guidelines prepared by the World Health Organization.

This work was in part supported by grant DOH94-DC-2028 from the Center for Disease Control, Department of Health, Taiwan, Republic of China.

References

  1. Anti-tuberculosis drug resistance in the world report no. 3 [monograph on the Internet]. [cited 2006 Mar 3]. Available from http://www.who.int/tb/publications/who_htm_tb_2004_343/en/index.html
  2. Center for Disease Control, Department of Health, Executive Yuan, Taiwan. Statistics of communicable diseases and surveillance report in Taiwan area, 2003 [monograph on the Internet]. [cited 2006 Mar 3]. Available from http://www.cdc.gov.tw/en/index.asp
  3. Chiang IH, Yu MC, Bai KJ, Wu MP, Hsu CJ, Lin TP, et al. Drug resistance patterns of tuberculosis in Taiwan. J Formos Med Assoc. 1998;97:581–3.
  4. Chiang CY, Hsu CJ, Huang RM, Lin TP, Luh KT. Antituberculosis drug resistance among retreatment tuberculosis patients in a referral center in Taipei. J Formos Med Assoc. 2004;103:411–5.
  5. Lu PL, Lee YW, Peng CF, Tsai JJ, Chen YH, Hwang KP, et al. The decline of high drug resistance rate of pulmonary Mycobacterium tuberculosis isolates from a southern Taiwan medical centre, 1996–2000. Int J Antimicrob Agents. 2003;21:239–43.

 

Table. Drug resistance patterns in Taiwan, 1960–2004

Hospital*

No. strains

Study period

Drug resistance (%)†

Methods

Reference‡


INH

EMB

RMP

SM

Any

MDR


Primary drug resistance

   A

162

1960–1962

13.4

11.7

22.2

Absolute concentration

(1)

   B

154

1962

8.4

7.8

14.3

(1)

   B

557

1971–1972

22.6

15.4

30.8

Resistance ratio on SM; absolute concentration on INH and EMB

(1)

   B

1,914

1979–1982

8.4

0.1

0

9.2

17.9

Absolute concentration

(1)

   B

1,924

1984–1988

6.8

0.4

0.2

5.0

9.9

Resistance ratio (1984–1986); absolute concentration (1986–1988)

(1)

   B

1,935

1990–1995

9.2

0.7

1.5

5.7

12.3

1.2

Absolute concentration

(1)

   B

249

1996

12.0

0.8

2.0

4.8

16.1

1.6

Absolute concentration

(2)

   C

254

1996–1999

4.7

5.9

5.9

11.0

22.0

1.6

Proportion

(3)

   D

456

2001–2002

14.9

2.6

3.3

11.4

20.6

2.4

BACTEC 960

(4)

   E

190

2001–2002

11.1

5.8

2.1

5.3

16.8

2.1

Proportion

(1)

   F

611

2002–2004

6.8

0.8

1.8

6.2

12.8

1.8

Proportion

NA

Acquired drug resistance

   B

200

1996

63.0

28.5

46.5

21.5

67.0

46.0

Absolute concentration

(2)

   C

199

1996–1999

25.6

11.1

32.2

17.1

49.2

15.1

Proportion

(3)

   B

183

2000–2001

37.7

10.9

25.1

17.5

42.6

24.6

Absolute concentration

(5)

   D

57

2001–2002

31.6

15.8

17.5

19.3

36.8

15.8

BACTEC 960

(4)

   E

62

2001–2002

54.8

33.9

45.2

17.7

64.5

45.2

Proportion

(1)

   F

324

2002–2004

50.9

12.6

44.4

17.9

55.8

42.2

Proportion

NA

Combined drug resistance

   G

942

1982–1986

20.4

15.3

8.8

9.8

27.8

8.1

Proportion

(6)

   A

651

1990–1992

14.7

10.3

10.6

11.2

22.6

8.3

Proportion

(4)

   G

884

1992–1996

20.9

12.8

11.8

9.1

28.9

10.1

Proportion

(6)

   B

1,091

1996

31.5

11.4

18.2

11.9

35.5

17.3

Absolute concentration

(2)

   C

453

1996–1999

13.9

8.2

17.4

13.7

34.0

7.5

Proportion

(3)

   H

693

1996–2000

35.9

15.7

13.4

28.6

52.4

11.4

Proportion

(7)

   I

1,411

1998–2002

19.0

15.7

6.1

10.0

30.5

5.1

Proportion

(8)

   D

513

2001–2002

16.8

4.1

4.9

12.3

22.4

3.9

BACTEC 960

(4)

   E

252

2001–2002

21.8

12.7

12.7

8.3

28.6

12.8

Proportion

(1)

   F

935

2002–2004

22.2

5.2

16.5

10.2

27.6

15.8

Proportion

NA


*A, Taipei Veterans General Hospital (medical center); B, Taiwan Provincial Chronic Disease Control Bureau (referral center); C, Taipei Municipal Chronic Disease Hospital (referral center); D, Changhua Christian Hospital (medical center); E, Buddhist Tzu Chi General Hospital (medical center); F, Chest Hospital (referral center); G, Chang–Gung Memorial Hospital (medical center); H, Kaohsiung Medical University Hospital (medical center); I, National Taiwan University Hospital (medical center).

†INH, isoniazid; EMB, ethambutol; RMP, rifampin; SM, streptomycin; Any, resistance to any 1 of INH, EMB, RMP, or SM; MDR, resistance to at least INH and RMP.

‡NA, not available.

Table References

  1. Lee JJ, Lee CN, Suo J, Chiang IH, Lin CB, Lin TY, et al. Drug resistance of Mycobacterium tuberculosis in eastern Taiwan. Tzu Chi Med J. 2003;15:229–34. Available from http://www.tzuchi.com.tw/tcmj/92-4/3.htm
  2. Chiang IH, Yu MC, Bai KJ, Wu MP, Hsu CJ, Lin TP, et al. Drug resistance patterns of tuberculosis in Taiwan. J Formos Med Assoc. 1998;97:581–3.
  3. Wang PD, Lin RS. Drug-resistant tuberculosis in Taipei, 1996–1999. Am J Infect Control. 2001;29:41–7. /li>
  4. Liu CE, Chen CH, Hsiao JH, Young TG, Tsay RW, Fung CP. Drug resistance of Mycobacterium tuberculosis complex in central Taiwan. J Microbiol Immunol Infect. 2004;37:295–300.
  5. Chiang CY, Hsu CJ, Huang RM, Lin TP, Luh KT. Antituberculosis drug resistance among retreatment tuberculosis patients in a referral center in Taipei. J Formos Med Assoc. 2004;103:411–5.
  6. Tsao TCY, Chiou W, Lin H, Wu T, Lin M, Yang P, et al. Change in demographic picture and increase of drug resistance in pulmonary tuberculosis in a 10-year interval in Taiwan. Infection. 2002;30:75–80.
  7. Lu PL, Lee YW, Peng CF, Tsai JJ, Chen YH, Hwang KP, et al. The decline of high drug resistance rate of pulmonary Mycobacterium tuberculosis isolates from a southern Taiwan medical centre, 1996–2000. Int J Antimicrob Agents. 2003;21:239–43.
  8. Liaw YS, Hsueh PR, Yu CJ, Wang SK, Yang PC, Luh KT. Drug resistance pattern of Mycobacterium tuberculosis in a university hospital in Taiwan, 1998–2002. J Formos Med Assoc. 2004;103:671–7.

 

Suggested citation for this article:
Jou R, Chuang P-C, Wu Y-S, Yan J-J, Luh K-T. Drug-resistant Mycobacterium tuberculosis, Taiwan [letter]. Emerg Infect Dis [serial on the Internet]. 2006 May [date cited]. Available from http://www.cdc.gov/ncidod/EID/vol12no05/05-1688.htm

   
     
   
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Ruwen Jou, Reference Laboratory of Mycobacteriology, Center for Research and Diagnostics, Center for Disease Control, Department of Health, 161 Kun-Yang Street, Nan-Kang, Taipei, 115, Taiwan, Republic of China; email: rwj@cdc.gov.tw

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