Comparison of Anti-mycobacterial Drug Susceptibility Test Results by Institutes and Methods

Seung Hwan Oh; Young Jin Kim; Seung Kyu Park; Sang Hyun Hwang; Hyung Hoi Kim; Eun Yup Lee; Chulhun L. Chang

doi:10.5145/kjcm.2008.11.1.43

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Oh, Kim, Park, Hwang, Kim, Lee, and Chang: Comparison of Anti-mycobacterial Drug Susceptibility Test Results by Institutes and Methods

Original Article

Korean J Clin Microbiol 2008;11(1):43-48.

Published online: 20 April 2008

DOI: https://doi.org/10.5145/kjcm.2008.11.1.43

Comparison of Anti-mycobacterial Drug Susceptibility Test Results by Institutes and Methods

Seung Hwan Oh^1,², Young Jin Kim¹, Seung Kyu Park², Sang Hyun Hwang¹, Hyung Hoi Kim¹, Eun Yup Lee¹, Chulhun L. Chang^1,^3,

¹Department of Laboratory Medicine, Pusan National University School of Medicine, Busan, Korea

²National Masan Hospital, Masan, Korea

³Korean Institute of Tuberculosis, Seoul, Korea

Chulhun L. Chang, Department of Laboratory Medicine, School of Medicine, Pusan National University, 10, Ami-dong 1-ga, Seo-gu, Busan 602-739, Korea. (Tel) 82-51-240-7417, (Fax) 82-51-247-6560, (E-mail) CCHL@pusan.ac.kr

Received 14 January 2008 Accepted 26 February 2008

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

Abstract

Background

The purposes of the current study were to evaluate the concordant rates of anti-mycobacterial drug susceptibility test (DST) results in different solid media performed in different institutes, and to determine reliable susceptible testing methods.

Methods

One hundred and twenty two Mycobacterium tuberculosis strains were isolated from patients in A Hospital in 2005. DSTs were performed by the absolute concentration method using Löwenstein Jensen medium in both A Hospital (method A-1) and B Institute (method B-1) and by the proportion method using Middlebrook 7H10 agar in B Institute (method B-2). Nine drugs were used including isoniazid and rifampin. Sensitivity and specificity of each method were estimated by using the acceptable standard of 90% for isoniazid and rifampin and 80% for other drugs. The therapeutic outcomes of quinolone-administered patients were evaluated according to ofloxacin susceptibility results.

Results

Method B-1 showed sensitivity and specific-ity levels over the acceptable standard levels for all drugs. Method B-2 showed specificity lower than the acceptable levels for rifampin and cycloserine. Method A-1 showed specificity lower than the acceptable levels for isoniazid, streptomycin, p-aminosalicylic acid, and ofloxacin and sensitivity lower than the acceptable levels for prothionamide and cycloserine. The concordance rates of therapeutic outcomes with method B-1, method B-2, and method A-1 were 77%, 74%, and 65%, respectively.

Conclusion

The drug susceptibility results for some drugs were discordant between the testing laboratories and media, requiring an urgent application of quality control programs to raise the reliability of an-ti-mycobacterial DST.

Keywords: Mycobacterium tuberculosis, Drug susceptibility tests, Culture Media

References

1. Kim BJ, Lee IH, Lee DH, Bai GH, Kong SJ, Lee SH, et al. The current status of multidrug-resistant tuberculosis in Korea. Tuberc Respir Dis. 2006; 60:404–11.

2. Vareldzis BP, Grosset J, de Kantor I, Crofton J, Laszlo A, Felten M, et al. Drug-resistant tuberculosis: laboratory issues. World Health Organization recommendations. Tuber Lung Dis. 1994; 75:1–7.

3. Canetti G, Fox W, Khomenko A, Mahler HT, Menon NK, Mitchison DA, et al. Advances in techniques of testing mycobacterial drug sensitivity, and the use of sensitivity tests in tuberculosis control programmes. Bull World Health Organ. 1969; 41:21–43.

4. Clinical and Laboratory Standards Institute. Susceptibility Testing of Mycobacteria, Nocardiae, and Other Aerobic Actinomycetes; Approved Standard. NCCLS document M24-A. Wayne, PA; NCCLS. 2003.

5. Mitchison DA. Drug resistance in tuberculosis. Eur Respir J. 2005; 25:376–9.

6. Kim SJ. Drug-susceptibility testing in tuberculosis: methods and reliability of results. Eur Respir J. 2005; 25:564–9.

7. Laszlo A, Rahman M, Espinal M, Raviglione M. WHO/IUATLD Network of Supranational Reference Laboratories. Quality assurance programme for drug susceptibility testing of Mycobacterium tuberculosis in the WHO/IUATLD Supranational Reference Laboratory Network: five rounds of proficiency testing, 1994–1998. Int J Tuberc Lung Dis. 2002; 6:748–56.

8. Mitarai S. The external quality assessment for Mycobacterium tuberculosis drug susceptibility testing by proficiency testing panel to the commercial laboratories. Kekkaku. 2005; 80:349–58.

9. World Health Organization. Guidelines for drug susceptibility testing for second-line anti-tuberculosis drufs for DOTS-PLUS. Publication No. WHO/CDS/TB/2001.288. Geneva; World Health Organization. 2001.

10. Pfyffer GE, Bonato DA, Ebrahimzadeh A, Gross W, Hotaling J, Kornblum J, et al. Multicenter laboratory validation of susceptibility testing of Mycobacterium tuberculosis against classical second-line and newer antimicrobial drugs by using the radiometric BACTEC 460 technique and the proportion method with solid media. J Clin Microbiol. 1999; 37:3179–86.

11. Bai GH, Kim SJ, Chang CL. National and Regional Tuberculosis Reference Laboratories. Proficiency analysis of drug susceptibility testing by national-level tuberculosis reference laboratories from 1995 to 2003. J Clin Microbiol. 2007; 45:3626–30.

12. Tomioka H. Prospects for development of new antimycobacterial drugs. J Infect Chemother. 2000; 6:8–20.

13. Tomioka H. Prospects for development of new antimycobacterial drugs, with special reference to a new benzoxazinorifamycin, KRM-1648. Arch Immunol Ther Exp (Warsz). 2000; 48:183–8.

Table 1.

Critical concentrations (μg/mL) of drugs

Methods∗	Drugs
Methods∗	INH	RIF	SM	EMB	PTH	KM	CS	PAS	OFX
A-1 & B-1	0.2	40	10	2	40	40	30	1	2
B-2	0.2/1	1	2/10	5/10	5	5	30	2	2

^∗ A-1, absolute concentration method in Löwenstein-Jensen medium in A Hospital; B-1 and B-2, absolute concentration method with Lö-wenstein-Jensen medium and proportion method with Middlebrook 7H10 agar in B Institute, respectively. Abbreviations: INH, isoniazid; RIF, rifampin; SM, streptomycin; EMB, ethambutol; PTH, prothionamide; KM, kanamycin; CS, cycloserine; PAS, para-amino salicylic acid; OFX, ofloxacin.

Table 2.

Test performance of each drug tested by three methods in two laboratories

	Method A-1∗			Method B-1∗		Method B-2∗
Drugs	Test results/Performance^†	True results		True results		True results
Drugs	Test results/Performance^†	R	S	R	S	R	S
INH	R	71	6	73	1	73	2
	S	3	42	1	47	1	46
	RD/SD	95.9 /	87.5	98.6 /	97.9	98.6 /	95.8
RIF	R	72	4	68	0	72	8
	S	1	45	5	49	1	41
	RD/SD	98.6 /	91.8	93.2 /	100	98.6 /	83.7
SM	R	25	19	29	0	26	1
	S	6	72	2	91	5	90
	RD/SD	80.6 /	79.1	93.5 /	100	83.9 /	98.9
EMB	R	57	12	57	0	60	11
	S	4	49	4	61	1	50
	RD/SD	93.4 /	80.3	93.4 /	100	98.4 /	82
PTH	R	15	1	34	5	33	6
	S	19	87	0	83	1	82
	RD/SD	44.1 /	98.9	100 /	94.3	97.1 /	93.2
KM	R	25	2	27	0	28	12
	S	3	92	1	94	0	82
	RD/SD	89.3 /	97.9	96.4 /	100	100 /	87.2
CS	R	13	0	15	0	16	64
	S	4	105	2	105	1	41
	RD/SD	76.5 /	100	88.2 /	100	94.1 /	39
PAS	R	37	26	35	0	37	1
	S	2	57	4	83	2	82
	RD/SD	94.9 /	68.7	89.7 /	100	94.9 /	98.8
OFX	R	42	45	42	0	41	0
	S	1	34	1	79	2	79
	RD/SD	97.7 /	43	97.7 /	100	95.3 /	100

^∗ Methods A-1, B-1, and B-2: See footnotes, Table 1.

^† Bold fonts indicate a poor (unacceptable) performance (in sensitivity or specificity) of corresponding tests. Abbreviations: R, resistant; S, susceptible; INH, isoniazid; RIF, rifampin; SM, streptomycin; EMB, ethambutol; PTH, prothionamide; KM, kanamycin; CS, cycloserine; PAS, para-amino salicylic acid; OFX, ofloxacin; RD, detection rates (%) of resistant strains or sensitivity; SD, detection rates (%) of susceptible strains or specificity.

Table 3.

Test efficiencies of each method in 57 patients with ofloxacin or levofloxacin prescription

Testing methods∗	Test results	No. of patients Test
Testing methods∗	Test results	Treatment failure	Treatment success	Sensitivity (%)	Specificity (%)	Test efficiencies (%)^†
A-1	R	24	16	85.7	44.8	64.9
	S	4	13
B-1	R	21	6	75.0	79.3	77.2
	S	7	23
B-2	R	19	6	67.9	79.3	73.7
	S	9	23

^∗ A-1, B-1, and B-2: See footnotes, Table 1.

^† Test efficiency = {(No. of patients with treatment failure whose isolates showed resistant to ofloxacin) + (No. of patients with treatment success whose isolates showed susceptible to ofloxacin)}/total No. of patients. Abbreviations: R, resistant; S, susceptible.

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