Giriş/Amaç: Tüberküloz, yüksek morbidite ve mortalite oranı ile önemli bir küresel sağlık sorunu olmaya devam etmektedir ve nüfusun yaklaşık dörtte biri tüberküloz ile enfektedir. İlaç duyarlılık testleri, ilaca dirençli tüberkülozu tanımlamak ve yönetmek için önemlidir. Bu çalışmada, bir üniversite hastanesinden izole edilen Mycobacterium tuberculosis compleks suşlarının ilaca duyarlılık paterninin değerlendirilmesi amaçlanmıştır.
Yöntemler: Ocak 2018-Ocak 2022 tarihleri arasında tüberküloz şüphesi ile mikrobiyoloji laboratuvarına gönderilen toplam 10900 örnek retrospektif olarak incelenmiştir. Örneklerin kültürü ve duyarlılık testleri için BACTEC MGIT 960 (Becton Dickinson, ABD) otomatize sistem kullanılmıştır. Elde edilen veriler Statistical Package for Social Sciences (SPSS version 20) ile istatistiksel olarak analiz edilmiştir.
Bulgular: Pozitif olarak bulunan 154 hastada erkek ve kadın oranı eşit olarak bulunmuştur. Tüberküloz olgularının çoğunluğu 56-75 yaş grubunda (%42,2) olup, hastaların %90,3'ünde akciğer tüberkülozu saptanırken, %9,7 oranında akciğer dışı tüberküloz tespit edilmiştir. Pozitif örnkelerde yapılan duyarlılık çalışmaları sonucunda izoniazid direnci %5,2; streptomisin direnci %1,3; etambutol direnci %0,6 oranında tespit edilirken, rifampisin dirençli örnek bulunmamıştır. Örneklerin %1,3’ünde hem streptomisin hem de izoniazid direnci birlikte görülmüştür.
Sonuç: Türkiye'de farklı illerde yapılan diğer çalışmalarda birinci basamak antitüberküloz ilaçlarda benzer direnç paterni gözlenmiştir. Çalışmamızda çok ilaca dirençli tüberküloz ve yaygın ilaca dirençli tüberküloz suşlarının bulunmaması, bölgemizde uygulanan tüberküloz sürveyans programınının başarılı olduğunu göstermektedir.
Diriba G, Alemu A, Tola HH, Eshetu K, Yenew B, Amare M, et al. Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis patients in Addis Ababa, Ethiopia from 2014 to 2021. IJID Regions. 2022; 5: 97–103.
Sah SK, Bhattarai PR, Shrestha A, Dhami D, Guruwacharya D, Shrestha R. Rifampicin-resistant Mycobacterium tuberculosis by Gene-Xpert MTB/RIF and Associated Factors among Presumptive Pulmonary Tuberculosis Patients in Nepal. Infect Drug Resist. 2020;13:2911–9.
Lavania M, Kunja Mohanty K, Sha W, Ameni G. Drug sensitivity of clinical isolates of Mycobacterium tuberculosis and its association with bacterial genotype in the Somali region, Eastern Ethiopia. Front Public Health. 2022;10:1–10.
Global Tuberculosis Report 2022 [Internet]. 2022. Available from: http://apps.who.int/bookorders.
Tuberculosis surveillance and monitoring in Europe 2022 – 2020 data. [Internet]. 2022. Available from: http://apps.who.int/bookorders.
Silas G, Ollor OA, Agi VN, Nwokah EG, Wokem GN, Enoch AS. Resistance Profile of Mycobacterial Strains Causing Cluster Pulmonary Infection in Bayelsa State, Nigeria. South Asian Journal of Research in Microbiology. 2022;13(1):1–7.
Terzi A, Aydemir Ö, Karakeçe E, Köroğlu M, Altındiş M. Changes in antituberculosis drug resistance rates of M. tuberculosis complex isolates by years; Sakarya. Online Türk Sağlık Bilimleri Dergisi. 2019;4(1):47–56.
Farra A, Manirakiza A, Yambiyo BM, Zandanga G, Lokoti B, Berlioz-Arthaud A, et al. Surveillance of rifampicin resistance with GeneXpert MTB/RIF in the National Reference Laboratory for tuberculosis at the Institut Pasteur in Bangui, 2015-2017. In Open forum infectious diseases (Vol. 6, No. 3, p. ofz075). US: Oxford University Press, 2019.
Iem V, Dean A, Zignol M, Vongvichit P, Inthavong D, Siphanthong S, et al. Low prevalence of MDR-TB in Lao PDR: results from the first national anti-tuberculosis drug resistance survey. Tropical Medicine and International Health. 2019; 24(4):421–31.
Yılmaz A, Afşin D. Investigation of the Sensitivity of Mycobacterium Tuberculosis Strains Isolated from Various Clinical Samples in Eastern Turkey to Major Anti-tuberculosis Drugs. Journal of Contemporary Medicine. 2021;11(1):92–6.
Faksri K, Kaewprasert O, Ong RTH, Suriyaphol P, Prammananan T, Teo YY, et al. Comparisons of whole-genome sequencing and phenotypic drug susceptibility testing for Mycobacterium tuberculosis causing MDR-TB and XDR-TB in Thailand. Int J Antimicrob Agents. 2019;54(2):109–16.
Behcet M, Karabork S, Avcioglu F, Karaibrahim A, Kurtoglu MG. Evaluation of the resistance patterns of Mycobacterium tuberculosis complex strains to antituberculous drugs. Experimental Biomedical Research. 2019;2(4):143–8.
Khursheed N, Asif S, Bano S, Ali MM, Adnan F. Susceptibility pattern of Mycobacterium tuberculosis over a period of five years at Indus Hospital and Health Network, Karachi, Pakistan. Pak J Med Sci. 2022;38:399–404.
Addo SO, Mensah GI, Mosi L, Abrahams AOD, Addo KK. Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses. IJID Regions. 2022;4:75–84.
Arrigoni R, Ballini A, Topi S, Bottalico L, Jirillo E, Santacroce L. Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents. Vol. 11, Antibiotics. MDPI; 2022.
Xu G, Liu H, Jia X, Wang X, Xu P. Mechanisms and detection methods of Mycobacterium tuberculosis rifampicin resistance: The phenomenon of drug resistance is complex. Vol. 128, Tuberculosis. Churchill Livingstone; 2021.
Mesfin EA, Merker M, Beyene D, Tesfaye A, Shuaib YA, Addise D, et al. Prediction of drug resistance by Sanger sequencing of Mycobacterium tuberculosis complex strains isolated from multidrug resistant tuberculosis suspect patients in Ethiopia. PLoS One. 2022;17(8): e0271508
Liu CF, Song YM, He P, Liu DX, He WC, Li YM, et al. Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of Mycobacterium tuberculosis. Biomedical and Environmental Sciences. 2021;34(8):616–22.
Mansoori N, Pahlavanzadeh B, Atarjalali M. A Report on Drug Resistance Patterns of Mycobacterium tuberculosis Isolates in Northern Iran. Arch Iran Med. 2022;25(3):161–5.
Tilahun M, Ameni G, Desta K, Zewude A, Yamuah L, Abebe M, et al. Molecular Epidemiology and Drug Sensitivity Pattern of MycobacteriumTuberculosis Strains Isolated from Pulmonary Tuberculosis Patients in and around Ambo Town, Central Ethiopia. PLoS One. 2018; 13(2): e0193083.
Quezel-Guerraz N, Sánchez-Porto A, Torres M, Santos Ma Jesús P, Federico A, Guzman A, et al. Antituberculosis Drug Resistance in Isolates of Mycobacterium tuberculosis complex in Southeast Spain. J Glob Antimicrob Resist. 2020;20:183–6.
Al-Shahrani MS, Hakami MI, Younis MA, Fan HA, Jeraiby MA, Alraey Y. Prevalence of Primary Anti-tuberculosis Drug Resistance at the Tertiary Center in Saudi Arabia and Associated Risk Factors. Saudi Med J. 2021;42(7):728–34.
Mohammed KAS, Khudhair GS, Al-Rabeai DB. Prevalence and Drug Resistance Pattern of Mycobacterium tuberculosis Isolated from Tuberculosis Patients in Basra, Iraq. Pol J Microbiol. 2022;71(2):205–15.
Mutayoba BK, Ershova J, Lyamuya E, Hoelscher M, Heinrich N, Kilale AM, et al. The second national anti-tuberculosis drug resistance survey in Tanzania, 2017–2018. Tropical Medicine and International Health. 2022;27(10):891–901.
Song WM, Li YF, Ma X Bin, Liu JY, Tao NN, Liu Y, et al. Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018. Respir Res. 2019;20(1):1-12
Balcı A, Günay E, Demir C, Çilekar Ş, Coşğun İG, Aydın S. Sensitivity Status of Mycobacterium tuberculosis Complex Strains Isolated in our Clinic to Antituberculosis Drugs. Kocatepe Medical Journal 2021;22:488-93
Aydın E, Tarhan G, Şahin F, Eren S. Molecular Epidemiological Typing of M. Tuberculosis Isolates Isolated From Turkey’s Eastern Anatolia With In-House PCR Method. Cukurova Medical Journal. 2022;47(1):191–8.
Aktaş A, Nakipoğlu Y, Şatana D. An Up-To-Date Overview of Our Country’s Data on Tuberculosis. Sakarya Medical Journal. 2022;12(3):586–95.
Öztürk T, Arıdoğan B, Çetin ES. Investigation of the Effectiveness of ‘Reverse Blot Hybridization Assay Mycobacterium tuberculosis Drug Resistance’ Method for the Rapid Diagnosis of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis Complex Clinical Isolates. SDÜ Tıp Fakültesi Dergisi . 2019;26(4):444–51.
Esenkaya Taşbent F, Doğan M. Resistance Rates of Mycobacterium tuberculosis Complex Strains to the Primary Anti-tuberculosis Drugs in Konya Province, Turkey. Turk Mikrobiyol Cem Derg. 2016;46(4):165–71. Available from: https://dx.doi.org/10.5222/TMCD.2016.165
Resistance Rates of Mycobacterium tuberculosis Complex Isolates to Primary Anti-tuberculosis Drugs: A 5-Year Retrospective Study
Background/Aim: Tuberculosis remains a major global health problem with a high morbidity and mortality rate, approximately a quarter of the population is infected with tuberculosis. Drug susceptibility testing is an essential tool for identifying and managing drug-resistant tuberculosis. This study was conducted to evaluate the drug susceptibility pattern of Mycobacterium tuberculosis complex strains isolated from a university hospital.
Methods: A total of 10900 samples sent to the microbiology laboratory with the suspicion of tuberculosis clinically between January 2018 and January 2022 were analyzed retrospectively. The automated BACTEC MGIT 960 (Becton Dickinson, USA) was used for sample culture and susceptibility testing. The obtained data were statistically analyzed with the Statistical Package for Social Sciences (SPSS version 20).
Results: Out of the 154 isolated positive samples, males and females constituted equal parts of the study population (50%). The majority of tuberculosis cases were in the age group 56–75 years (42.2%), Pulmonary TB was detected in (90.3%) of the patients, while extrapulmonary TB cases were observed in (9.7%). As a result of susceptibility studies on positive samples, isoniazid resistance was 5.2%; streptomycin resistance 1.3%; ethambutol resistance was detected at a rate of 0.6%, while no rifampicin resistant sample was found. Both streptomycin and isoniazid resistance were seen together in 1.3% of the samples.
Conclusion: A similar resistance pattern of the first-line antituberculosis drugs was observed in other studies conducted in different provinces of Turkey. The absence of multi-drug resistant and extensively drug-resistant tuberculosis in our study indicates that the tuberculosis surveillance program implemented in our region was successful.
Diriba G, Alemu A, Tola HH, Eshetu K, Yenew B, Amare M, et al. Detection of Mycobacterium tuberculosis and rifampicin resistance by Xpert® MTB/RIF assay among presumptive tuberculosis patients in Addis Ababa, Ethiopia from 2014 to 2021. IJID Regions. 2022; 5: 97–103.
Sah SK, Bhattarai PR, Shrestha A, Dhami D, Guruwacharya D, Shrestha R. Rifampicin-resistant Mycobacterium tuberculosis by Gene-Xpert MTB/RIF and Associated Factors among Presumptive Pulmonary Tuberculosis Patients in Nepal. Infect Drug Resist. 2020;13:2911–9.
Lavania M, Kunja Mohanty K, Sha W, Ameni G. Drug sensitivity of clinical isolates of Mycobacterium tuberculosis and its association with bacterial genotype in the Somali region, Eastern Ethiopia. Front Public Health. 2022;10:1–10.
Global Tuberculosis Report 2022 [Internet]. 2022. Available from: http://apps.who.int/bookorders.
Tuberculosis surveillance and monitoring in Europe 2022 – 2020 data. [Internet]. 2022. Available from: http://apps.who.int/bookorders.
Silas G, Ollor OA, Agi VN, Nwokah EG, Wokem GN, Enoch AS. Resistance Profile of Mycobacterial Strains Causing Cluster Pulmonary Infection in Bayelsa State, Nigeria. South Asian Journal of Research in Microbiology. 2022;13(1):1–7.
Terzi A, Aydemir Ö, Karakeçe E, Köroğlu M, Altındiş M. Changes in antituberculosis drug resistance rates of M. tuberculosis complex isolates by years; Sakarya. Online Türk Sağlık Bilimleri Dergisi. 2019;4(1):47–56.
Farra A, Manirakiza A, Yambiyo BM, Zandanga G, Lokoti B, Berlioz-Arthaud A, et al. Surveillance of rifampicin resistance with GeneXpert MTB/RIF in the National Reference Laboratory for tuberculosis at the Institut Pasteur in Bangui, 2015-2017. In Open forum infectious diseases (Vol. 6, No. 3, p. ofz075). US: Oxford University Press, 2019.
Iem V, Dean A, Zignol M, Vongvichit P, Inthavong D, Siphanthong S, et al. Low prevalence of MDR-TB in Lao PDR: results from the first national anti-tuberculosis drug resistance survey. Tropical Medicine and International Health. 2019; 24(4):421–31.
Yılmaz A, Afşin D. Investigation of the Sensitivity of Mycobacterium Tuberculosis Strains Isolated from Various Clinical Samples in Eastern Turkey to Major Anti-tuberculosis Drugs. Journal of Contemporary Medicine. 2021;11(1):92–6.
Faksri K, Kaewprasert O, Ong RTH, Suriyaphol P, Prammananan T, Teo YY, et al. Comparisons of whole-genome sequencing and phenotypic drug susceptibility testing for Mycobacterium tuberculosis causing MDR-TB and XDR-TB in Thailand. Int J Antimicrob Agents. 2019;54(2):109–16.
Behcet M, Karabork S, Avcioglu F, Karaibrahim A, Kurtoglu MG. Evaluation of the resistance patterns of Mycobacterium tuberculosis complex strains to antituberculous drugs. Experimental Biomedical Research. 2019;2(4):143–8.
Khursheed N, Asif S, Bano S, Ali MM, Adnan F. Susceptibility pattern of Mycobacterium tuberculosis over a period of five years at Indus Hospital and Health Network, Karachi, Pakistan. Pak J Med Sci. 2022;38:399–404.
Addo SO, Mensah GI, Mosi L, Abrahams AOD, Addo KK. Genetic diversity and drug resistance profiles of Mycobacterium tuberculosis complex isolates from patients with extrapulmonary tuberculosis in Ghana and their associated host immune responses. IJID Regions. 2022;4:75–84.
Arrigoni R, Ballini A, Topi S, Bottalico L, Jirillo E, Santacroce L. Antibiotic Resistance to Mycobacterium tuberculosis and Potential Use of Natural and Biological Products as Alternative Anti-Mycobacterial Agents. Vol. 11, Antibiotics. MDPI; 2022.
Xu G, Liu H, Jia X, Wang X, Xu P. Mechanisms and detection methods of Mycobacterium tuberculosis rifampicin resistance: The phenomenon of drug resistance is complex. Vol. 128, Tuberculosis. Churchill Livingstone; 2021.
Mesfin EA, Merker M, Beyene D, Tesfaye A, Shuaib YA, Addise D, et al. Prediction of drug resistance by Sanger sequencing of Mycobacterium tuberculosis complex strains isolated from multidrug resistant tuberculosis suspect patients in Ethiopia. PLoS One. 2022;17(8): e0271508
Liu CF, Song YM, He P, Liu DX, He WC, Li YM, et al. Evaluation of Multidrug Resistant Loop-mediated Isothermal Amplification Assay for Detecting the Drug Resistance of Mycobacterium tuberculosis. Biomedical and Environmental Sciences. 2021;34(8):616–22.
Mansoori N, Pahlavanzadeh B, Atarjalali M. A Report on Drug Resistance Patterns of Mycobacterium tuberculosis Isolates in Northern Iran. Arch Iran Med. 2022;25(3):161–5.
Tilahun M, Ameni G, Desta K, Zewude A, Yamuah L, Abebe M, et al. Molecular Epidemiology and Drug Sensitivity Pattern of MycobacteriumTuberculosis Strains Isolated from Pulmonary Tuberculosis Patients in and around Ambo Town, Central Ethiopia. PLoS One. 2018; 13(2): e0193083.
Quezel-Guerraz N, Sánchez-Porto A, Torres M, Santos Ma Jesús P, Federico A, Guzman A, et al. Antituberculosis Drug Resistance in Isolates of Mycobacterium tuberculosis complex in Southeast Spain. J Glob Antimicrob Resist. 2020;20:183–6.
Al-Shahrani MS, Hakami MI, Younis MA, Fan HA, Jeraiby MA, Alraey Y. Prevalence of Primary Anti-tuberculosis Drug Resistance at the Tertiary Center in Saudi Arabia and Associated Risk Factors. Saudi Med J. 2021;42(7):728–34.
Mohammed KAS, Khudhair GS, Al-Rabeai DB. Prevalence and Drug Resistance Pattern of Mycobacterium tuberculosis Isolated from Tuberculosis Patients in Basra, Iraq. Pol J Microbiol. 2022;71(2):205–15.
Mutayoba BK, Ershova J, Lyamuya E, Hoelscher M, Heinrich N, Kilale AM, et al. The second national anti-tuberculosis drug resistance survey in Tanzania, 2017–2018. Tropical Medicine and International Health. 2022;27(10):891–901.
Song WM, Li YF, Ma X Bin, Liu JY, Tao NN, Liu Y, et al. Primary drug resistance of mycobacterium tuberculosis in Shandong, China, 2004-2018. Respir Res. 2019;20(1):1-12
Balcı A, Günay E, Demir C, Çilekar Ş, Coşğun İG, Aydın S. Sensitivity Status of Mycobacterium tuberculosis Complex Strains Isolated in our Clinic to Antituberculosis Drugs. Kocatepe Medical Journal 2021;22:488-93
Aydın E, Tarhan G, Şahin F, Eren S. Molecular Epidemiological Typing of M. Tuberculosis Isolates Isolated From Turkey’s Eastern Anatolia With In-House PCR Method. Cukurova Medical Journal. 2022;47(1):191–8.
Aktaş A, Nakipoğlu Y, Şatana D. An Up-To-Date Overview of Our Country’s Data on Tuberculosis. Sakarya Medical Journal. 2022;12(3):586–95.
Öztürk T, Arıdoğan B, Çetin ES. Investigation of the Effectiveness of ‘Reverse Blot Hybridization Assay Mycobacterium tuberculosis Drug Resistance’ Method for the Rapid Diagnosis of Isoniazid and Rifampicin Resistance in Mycobacterium tuberculosis Complex Clinical Isolates. SDÜ Tıp Fakültesi Dergisi . 2019;26(4):444–51.
Esenkaya Taşbent F, Doğan M. Resistance Rates of Mycobacterium tuberculosis Complex Strains to the Primary Anti-tuberculosis Drugs in Konya Province, Turkey. Turk Mikrobiyol Cem Derg. 2016;46(4):165–71. Available from: https://dx.doi.org/10.5222/TMCD.2016.165
Ibnouf SAA, Esenkaya Taşbent F. Resistance Rates of Mycobacterium tuberculosis Complex Isolates to Primary Anti-tuberculosis Drugs: A 5-Year Retrospective Study. Genel Tıp Derg. 2024;34(2):190-4.