Investigation of the Sensitivity of Mycobacterium Tuberculosis Strains Isolated from Various Clinical Samples in Eastern Turkey to Major Anti-tuberculosis Drugs

Abstract

Objective: In the study, 419 Mycobacterium tuberculosis complex strains (MTC), which were isolated from samples sent to the Regional Tuberculosis Laboratory in our city between 2015 and 2019 with suspected tuberculosis from Erzurum and surrounding cities were investigated. Methods: Our research is a retrospective cross-sectional study and clinical samples sent to the Regional Public Health Laboratory with suspicion of Tuberculosis within a five-year period from January 2015 to December 2019 were first evaluated by using Ehrlich-Ziehl-Neelsen staining technique. The samples were then simultaneously inoculated into the automated culture system (BACTEC MGIT 960) with Löwenstein-Jensen medium. Sensitivity research was conducted for isoniazide, rifampicin, streptomycin and ethambutol antibiotics with BACTEC MGIT 960 system to samples defined by MTC identification test (TBc ID) from reproduction positive tubes. Results: In our study, 337 (80.4%) of the 419 MTC strains investigated in our study were susceptible to all major anti-TB drugs, while 82 (19.6%) were found to be resistant to at least one major anti-TB drug. The distribution of resistance ratios was isoniazid (11.9%), streptomycin (11.7%), rifampicin (4.1%), ethambutol (3.6%). Multi-drug resistant (MDR)–TB ratio (isoniazid+ rifampicin) was found to be (3.6%). Conclusions: In our study, in the strains in which resistance to anti-TB drugs was investigated, the highest drug resistance was determined for isoniazid. The lowest drug resistance was determined for ethambutol.

Keywords

• Mycobacterium tuberculosis
• drug resistance,
• çoklu ilaç dirençli(ÇİD) tüberküloz
• anti-tuberküloz ilaçlar

Türkiyenin Doğusunda Çeşitli Klinik Örneklerden İzole Edilen Mycobacterium tuberculosis Suşlarinin Major Anti-Tüberküloz İlaçlara Duyarlılıklarının Araştırılması

Abstract

Amaç: Çalışmada ilimizde bulunan Bölge Tüberküloz Laboratuvarı’na 2015-2019 yılları arasında Erzurum ve çevre illerden tüberküloz şüphesi ile gönderilen örneklerden izole edilmiş olan 419 Mycobacterium tuberculosis kompleks suşun(MTK), major anti-tuberküloz ilaçlara karşı direnç durumu araştırıldı. Gereç ve Yöntem: Araştırmamız retrospektif kesitsel bir çalışma olup, Ocak 2015-Aralık 2019 tarihleri arası beş yıllık sürede Bölge Halk Sağlığı Laboratuvarına Tüberküloz şüphesiyle gönderilen klinik örnekler, ilk önce Ehrlich-Ziehl-Neelsen boyama yöntemi kullanılarak değerlendirildi. Daha sonra örnekler eş zamanlı olarak Löwenstein-Jensen besiyeri ile otomatize kültür sistemine (BACTEC MGIT 960) ekimleri yapıldı. Üremesi pozitif tüplerden identifikasyon testi (TBc ID) ile MTK tanımlaması yapılan örneklere BACTEC MGIT 960 sistemi ile izoniazid, rifampisin, streptomisin ve etambutol antibiyotikleri için duyarlılık araştırması yapıldı. Bulgular: Çalışmamızda ilaç duyarlılığı araştırılan 419 MTK suş’un 337’si (%80,4) majör anti-TB ilaçların tümüne duyarlı iken 82’si (%19,6) en az bir majör anti-TB ilaca dirençli bulundu. Direnç oranlarının dağılımı izoniazid (%11,9), streptomisin (%11,7), rifampisin (%4,1), etambutol (%3,6) idi. Çoklu ilaca dirençli(ÇİD)–TB oranı (izoniazid+ rifampisin) (%3.6) olarak bulundu. Sonuç: Çalışmamızda majör anti-TB ilaçlara karşı direnç araştırılan suşlarda en yüksek ilaç direnci izoniazid için belirlendi. En düşük ilaç direnci etambutol için saptandı.

Keywords

• Mycobacterium tuberculosis
• ilaç direnci
• çoklu ilaç dirençli(ÇİD) tüberküloz
• anti-tuberküloz ilaçlar

References

1. 1. Murray CJ, Ortblad KF, Guinovart C, Lim SS, Wolock TM, Roberts DA, Dansereau EA, Graetz N, Barber RM, Brown JC, et al. Global, regional, and national incidence and mortality for HIV, tuberculosis, and malaria during 1990–2013: a systematic analysis for the Global Burden of Disease Study 2013. Lancet. 2014; 384 (9947): 1005-1070. https://doi.org/10.1016/S0140-6736(14)60844-8
2. 2. Kyu HH, Maddison ER, Henry NJ, Mumford JE, Barber R, Shields C, Brown JC, Nguyen J, Carter A, Wolock TM, et al. The global burden of tuberculosis: results from the Global Burden of Disease Study 2015. Lancet Infect Dis. 2018; 18(3): 261-84. https://doi.org/10.1016/S1473-3099(17)30703-X
3. 3. Global tuberculosis report 2019. Geneva: World Health Organization; 2019. Licence: CC BY-NC-SA 3.0 IGO. https://www.who.int/tb/publications/global_report/en/
4. 4. Republic of Turkey Ministry of Health, General Directorate of Public Health, Tuberculosis Diagnosis and Treatment Guidelines. Ministry of Health Publication No: 1129, Ankara 2019.
5. 5. Ozkara S. 2007. Extensive drug resistant tuberculosis (XDR-TB). Solunum Hastalıkları 2007; 18(2): 88-92
6. 6. Baylan O. Treatment of drug-resistant tuberculosis. Turkiye Klinikleri J Med Sci. 2012; 32(3): 788-804. doi: 10.5336/medsci.2011-24602
7. 7. Colijn C, Cohen T, Ganesh A, Murray M. Spontaneous emergence of multiple drug resistance in tuberculosis before and during therapy. PLoS ONE. 2011; 6(3): e18327. https://doi.org/10.1371/journal.pone.0018327
8. 8. Sharma A, Hill A, Kurbatova E, van der Walt M, Kvasnovsky C, Tupasi TE, Caoili JC, Gler MT, Volchenkov GV, Kazennyy BY, et al. Estimating the future burden of multidrug-resistant and extensively drug-resistant tuberculosis in India, the Philippines, Russia, and South Africa: a mathematical modelling study. Lancet Infect Dis. 2017; 17(7): 707-715. doi: 10.1016/S1473-3099(17)30247-5

9. 9. Artan C, Deniz E, Biraderoglu H, Atan A, Artan M. Evaluation of primer antituberculosis drug susceptibilities of Mycobacterium tuberculosis complex strains isolated from respiratory tract samples. ANKEM Derg. 2013; 27(4): 179-183. doi: 10.26453/otjhs.441168
10. 10. Bektore B, Haznedaroglu T, Baylan O, Ozyurt M, Ozkutuk N, Satana D, Cavusoglu C, Seber E. Investigation of extensive drug resistance in multidrug resistance tuberculosis isolates. Mikrobiyol Bul. 2013; 47(1): 59-70. doi: 10.5578/mb.4229
11. 11. Esenkaya Tasbent F, Dogan M. Resistance rates of Mycobacterium tuberculosis complex strains to the primary anti-tuberculosis drugs in Konya province, Turkey. Türk Mikrobiyol Cem Derg. 2016; 46(4); 165-171. doi: 10.5222/TMCD.2016.165
12. 12. Burak Selek M, Baylan O, Gorenek L. Investigation of first-line antituberculosis drug susceptibility testing of Mycobacterium tuberculosis complex isolates in a Training and Research Hospital among the 2010-2016 Years. Nobel Medicus Journal. 2019, 15(2), 40-46
13. 13. Adane K, Ameni G, Bekele S, Abebe M, Aseffa A. Prevalence and drug resistance profile of Mycobacterium tuberculosis isolated from pulmonary tuberculosis patients attending two public hospitals in East Gojjam zone, northwest Ethiopia. BMC Public Health. 2015, 15(1), 572. doi:10.1186/s12889-015-1933-9
14. 14. Lee HY, Lee J, Lee YS, Kim MY, Lee HK, Lee YM, Shin JH, Ko Y. Drug-resistance pattern of Mycobacterium tuberculosis strains from patients with pulmonary and extrapulmonary tuberculosis during 2006 to 2013 in a Korean tertiary medical center. Korean J Intern Med. 2015, 30(3), 325-34. doi: 10.3904/kjim.2015.30.3.325
15. 15. He XC, Zhang XX, Zhao JN, Liu Y, Yu CB, Yang GR, Li HC. Epidemiological trends of drug-resistant tuberculosis in China from 2007 to 2014: A retrospective study. Medicine (Baltimore). 2016; 95(15): e3336. doi: 10.1097/MD.0000000000003336 16. Türkiye'de Verem Savaşı 2018 Raporu. Republic of Turkey Ministry of Health, General Directorate of Public Health: Ankara, 2018. https://hsgm.saglik.gov.tr/depo/birimler/tuberkuloz_db/dosya/raporlar/Turkiye_de_Verem_Savas_2018_Raporu_kapakl_.pdf
16. 17 Maurya AK, Kant S, Nag VL, Kushwaha RA, Dhole TN. Trends of anti-tuberculosis drug resistance pattern in new cases and previously treated cases of extrapulmonary tuberculosis cases in referral hospitals in northern India. J Postgrad Med. 2012; 58(3): 185- 189. doi: 10.4103/0022-3859.101379
17. 18 Yu CC, Chang CY, Liu CE, Shih LF, Hsiao JH, Chen CH. Drug resistance pattern of Mycobacterium tuberculosis complex at a medical center in central Taiwan, 2003–2007. J Microbiol Immunol Infect. 2010; 43(4): 285-290. doi: 10.1016/S1684-1182(10)60045-X
18. 19. Aktas AE, Yigit N, Ayyildiz A, Bastopcu A. Comparison of the mycobacterium growth indicator tube method and the method of proportion for drug susceptibility testing of mycobacterium tuberculosis. Eurasian J Med. 2014; 46(2): 96-101. doi: 10.5152/eajm.2014.23
19. 20. Hattori T, Kobayashi N, Nagai H, Chagan-Yasutan H, Telan E, Solante MB. Nationwide HIV-MDR-TB survey in Japan and collaborative study in the Philippines. Int J Mycobacteriol. 2016; 5 Suppl 1(5): 18-19. doi: 10.1016/j.ijmyco.2016.09.009
20. 21. Lisdawati V, Puspandari N, Rif'ati L, Soekarno T, Melatiwati M, Siyamsidar K, Ratnasari L, Izzatun N, Parwati I. Molecular epidemiology study of Mycobacterium tuberculosis and its susceptibility to anti-tuberculosis drugs in Indonesia. BMC Infect Dis. 2015; 15(1): 366. doi: 10.1186/s12879-015-1101-y
21. 22. Solomon A, Beckert P, Haileamlak A, Wieser A, Pritsch M, Heinrich N, Löscher T, Hoelcscher M, Nierman S, Rachow A. Drug resistance and population structure of M. tuberculosis isolates from prisons and communities in Ethiopia. BMC Infect Dis. 2016; 16(1): 687. doi: 10.1186/s12879-016-2041-x
22. 23. Akhtar AM, Arif MA, Kanwal S, Majeed S. Prevalence and drug resistance pattern of MDR TB in retreatment cases of Punjab, Pakistan. J Pak Med Assoc. 2016; 66(8): 989-993.
23. 24. Ozmen E, Aslan A, Ucar M, Aydin H, Yilmaz A. Resistance Ratios of Mycobacterium tuberculosis complex strains isolated in Erzurum Regional Tuberculosis Laboratory against Major Antituberculosis Drugs. ANKEM Derg. 2017; 31(2): 53-58. doi: 10.5222/ankem.2017.053