Resistance patterns and trends of extensively drug-resistant tuberculosis: 5-year experience

Abstract

Objective: Extensively drug-resistant tuberculosis (XDR-TB) strains were emerged when multidrug-resistant TB (MDR-TB) was inadequately treated. Inadequate treatment of MDR-TB cases may result in additional resistance especially non-XDR-TB and then XDR-TB. The aim of this study was to know the prevalence, resistance patterns and trends of the XDR-TB strains among the MDR-TB at a tertiary care hospital in Lucknow, India Methods: A total of 430 Mycobacterium isolates were underwent NAP test and TB MPT64 Ag test for the identification of Mycobacterium tuberculosis complex (MTBC). Drug-susceptibility test (DST) was performed over MTBC for the first line drugs by 1% proportion method (Bactec) and for the second-line drugs by 1% proportion method (Lowenstein-Jensen media). The XDR-TB status was further confirmed by line probe assay (GenoType® MTBDRsl assay). Results: Among the 430 isolates of mycobacterium, 365 (84.9%) were MTBC and 139 (38.1%) were MDR-TB respectively. Further 97 MDR-TB from "highly suspected drug resistant-TB (DR-TB)" cases among MDR-TB were tested with second line drugs in which 15 (15.5%) XDR-TB and 82 (84.5%) were non-XDR-TB. Regarding XDR-TB status, using the 1% proportion method a 100% agreement was seen with the GenoType® MTBDRsl assay. Resistance patterns of XDR-TB were as; 10/15 (66.7%) as isoniazid + rifampicin + ciprofloxacin + amikacin resistance and 5/15 (33.3%) as isoniazid + rifampicin + ciprofloxacin + amikacin + kanamycin resistance. Conclusion: The prevalence of XDR-TB was 15.5% among MDR-TB. Hence laboratory testing of "highly suspected drug resistant-TB" isolates should be done for both first and second line drugs simultaneously especially in developing countries.

Keywords

• Mycobacterium tuberculosis, extensively drug-resistant tuberculosis, multi drug-resistance tuberculosis, India

Resistance patterns and trends of extensively drug-resistant tuberculosis: 5-year experience

Öz

Amaç: Genişlemiş drug-rezistan tüberküloz (XDR-TB) suşları multi-drug rezistan tüberküloz (MDR-TB) suşlarının uygunsuz tedavisiyle önem kazandı. Multi-drug rezistan tüberküloz (MDR-TB) suşları ile infekte olguların uygunsuz tedavisi özellikle XDR-TB dışı ve XDR-TB’a yol açabilir. Bu çalışmada Hindistan’ın Luckdown şehrindeki bir üçüncü basamak hastanesinde multidrug-rezistan tüberküloz suşları arasında genişlemiş drug-rezistans paterni ve trendinin araştırılması amaçlandı. Yöntemler: Çalışmada Mycobacteruim tuberculosis complex (MTBC) identifikasyonu için 430 mikobakteri suşu NAP testi ve TB MPT64 Ag testine tabi tutuldu. İlaç duyarlılıklarının belirlenmesinde ilk sıra ilaçlar için % 1 proporsiyon metodu (Bactec) XDR-TB durumu GenoType® MTBDRslassay ile doğrulandı.Bulgular: Toplam 430 mikobakteriden 365’i (% 84,9) MTBC ve 139’u (% 38,1) MDR-TB olarak tanımlandı. Yüksek oranda drug-rezistan-TB (DR-TB) olarak düşünülen 97 MDR-TB suşu ikinci sıra antitüberküloz ilaçlara duyarlılık açısındn test edildiğinde suşlardan 15’i (% 15,5) XDR-TB ve 82’si (% 84,5) ise XDR-TB dışı suşlar idi. XDR-TB suşlarının tamamı %1 proporsiyon testi kullanılarak GenoType® MTBDRsl assay ile doğrulandı. Toplam 15 XDR-TB suşundan 10’u (% 66,7) izoniazid + rifampisin + siprofloksazin + amikasin ve 5’i (% 33,3%) izoniazid + rifampisin + siprofloksazin + amikasin + kanamisin’e dirençli olarak değerlendirildi.Sonuç: Bu çalışmada MDR-TB suşları arasında XDR-TB prevalansı % 15,5 olarak bulunmuştur. Bu yüzden özellikle gelişmekte olan ülkelerde yüksek şüpheli drug-rezistan TB durumunda suşların ilk ve ikinci sıra antitüberküloz ilaçlara duyarlılığının birlikte araştırılması gerektiğini düşünüyoruz

Anahtar Kelimeler

• Mycobacterium tuberculosis, genişlemiş drug-rezistan tüberküloz, multidrug-rezistan tüberküloz, Hindistan

References

1. 1. World Health Organization. Global Tuberculosis Control-Surveillance, Planning, Financing. World Health Organization Report, Geneva, Switzerland: WHO, 2008. http:// www.who. int/ tb/ publications/ global report/ 2008/en/index.html [Last Accessed on 5 August 2012].
2. 2. A Directorate of Health Services, Ministry of Health & family welfare, www.tbcindia.org, 2009. [Last Accessed on 2 April 2012].
3. 3. Steinbrook R. Tuberculosis and HIV in India. N Engl J Med 2007; 356:1198-1199.
4. 4. Nathanson E, Nunn P, Uplekar M et al. MDR tuberculosiscritical steps for prevention and control. N Engl J Med 2010;363:1050-1058.
5. 5. Zignol M, Hosseini MS, Wright A, et al. Global incidence of multidrug-resistant tuberculosis. J Infect Dis 2006; 194:479- 485.
6. 6. Maurya AK, Kant S, Kushwaha RAS, Nag VL. Extensively drug resistance Tuberculosis - New generation of drug resistance. J Bioscience and Technology 2011;2:312-317.
7. 7. Kant S, Maurya AK, Kushwaha RA, Nag VL, Prasad R. Multidrug resistant tuberculosis: an iatrogenic problem. Biosci Trends 2010;4:48-55.
8. 8. Kubica GP, Gontijo-Filho PP, Kim T. Preservation of mycobacteria st -70 degrees C: persistence of key differential features. J Clin Microbiol 1977;6:149-153.

9. 9. Siddiqui SH. BACTEC 460 TB system. Product and procedure manual. Becton Dickinson Microbiology System. Sparks, MD. 1996.
10. 10. Maurya AK, Nag VL, Kant S, et al. Evaluation of an immunochromatographic test for discrimination between Mycobacterium tuberculosis complex & non tuberculous mycobacteria in clinical isolates from extra-pulmonary tuberculosis. Indian J Med Res 2012; 135:901-906.
11. 11. Ismail NA, Baba K, Pombo D, Hoosen AA. Use of an immunochromatographic kit for the rapid detection of Mycobacterium tuberculosis from broth cultures. Int J Tuberc Lung Dis 2009;13:1045-1047.
12. 12. Canetti G, Froman S, Grosset J, et al. Mycobacteria: Laboratory Methods for Testing Drug Sensitivity and Resistance. Bull World Health Organ 1963; 29:565-578.
13. 13. World Health Organization. Guidelines for drug susceptibility testing for second line anti-tuberculosis drugs for DOTSPlus: WHO/CDS/TB/2001.288, Geneva, Switzerland (accessed August 28 2012).
14. 14. Mondal R, Jain A. Extensively drug-resistant Mycobacterium tuberculosis, India. Emerg Infect Dis 2007;13:1429-1431.
15. 15. Hillemann D, Rusch-Gerdes S, Richter E. Feasibility of the GenoType® MTBDRsl assay for fluoroquinolone, amikacincapreomycin, and ethambutol resistance testing of Mycobacterium tuberculosis strains and clinical specimens. J Clin Microbiol 2009; 47:1767-1772.
16. 16. World Health Organization. Joint United Nations Programme on HIV/AIDS (UNAIDS)-WHO. Revised recommendations for the selection and use of HIV antibody tests. Wkly Epidemiol Rec 1997; 72: 81–87.
17. 17. Sharma SK, George N, Kadhiravan T et al. Prevalence of extensively drug-resistant tuberculosis among patients with multidrug-resistant tuberculosis: a retrospective hospitalbased study. Indian J Med Res 2009;130:392-395.
18. 18. Datta BS, Hassan G, Kadri SM, et al. Multidrug-resistant and extensively drug-resistant tuberculosis in Kashmir, India. J Infect Dev Ctries 2010; 4:19-23.
19. 19. World Health Organization. Towards universal access to diagnosis and treatment of multidrug-resistant and extensively drug-resistant tuberculosis by 2015. WHO progress report 201.WHO/HTM/TB/2011.3. Geneva: World Health Organization. 2011.
20. 20. Shah NS, Richardson J, Moodley P, et al. Increasing drug resistance in extensively drug-resistant tuberculosis, South Africa. Emerg Infect Dis 2011; 17:510-513.
21. 21. Deivanayagam CN, Rajasekaran S, Venkatesan R et al. Prevalence of acquired MDR-TB and HIV co-infection. Indian J Chest Dis Allied Sci 2002; 44:237-242.
22. 22. Singh S, Sankar MM, Gopinath K. High rate of extensively drug-resistant tuberculosis in Indian AIDS patients. AIDS 2007;21:2345-2347.
23. 23. Gandhi NR, Shah NS, Andrews JR, et al. HIV coinfection in multidrug- and extensively drug-resistant tuberculosis results in high early mortality. Am J Respir Crit Care Med 2010;181:80-86.
24. 24. Sun Z, Zhang J, Song H, et al. Concomitant increases in spectrum and level of drug resistance in Mycobacterium tuberculosis isolates. Int J Tuberc Lung Dis 2010;14:1436- 1441.
25. 25. Crofton J, Chaulet P, Maher D. Guidelines for the management of drug-resistant tuberculosis. Geneva, Switzerland: World Health Organization 1997;1-40.