Hubungan Kepatuhan Pasien Tuberkulosis Paru Mengkonsumsi Isoniazid Selama Pengobatan Obat Anti Tuberkulosis dengan Mutasi Gen katG Ser315thr (G944c) Mycobacterium Tuberculosis
Abstract
Abstrak: Mutasi pada gen Mycobacterim tuberculosis merupakan penyebab utama terjadinya resistensi terhadap obat anti tuberkulosis (OAT) oleh karena kadar terapi yang inadekuat akibat ketidakpatuhan selama mengkonsumsi obat. Mutasi pada gen katG Ser315Thr (G944C) merupakan salah mutasi yang terjadi akibat ketidakadekuatan dosis isoniazid (INH) . Penelitian kohort dilakukan terhadap 100 pasien TB paru BTA positif yang akan mulai mengkonsumsi INH di Rumah Sakit Umum dr. Pirngadi Medan, yang belum mengalami mutasi gen katG Ser315Thr (G944C) M tuberculosis. Penelitian ini bertujuan untuk mengetahui hubungan antara kepatuhan pasien TB paru mengkonsumsi INH selama pengobatan OAT dengan terjadinya mutasi gen katG Ser315Thr (G944C). Kepatuhan dinilai dengan pemeriksaan metabolit INH urin metode Arkansas menggunakan Taxo urine test strip sedangkan mutasi gen dengan metode PCR-RFLP. Turut dinilai karakteristik sosiodemografi penderita TB paru pada penelitian ini serta hubungannya dengan kepatuhan dalam mengkonsumsi INH selama pengobatan OAT. Hasil penelitian tidak dijumpai adanya mutasi gen katG Ser315Thr (G944C) M tuberculosis, baik pada kelompok penderita TB paru yang patuh (84%) maupun tidak patuh (16%) mengkonsumsi INH (100% wild type). Berdasarkan karakteristik sosiodemografi, tidak dijumpai hubungan antara umur, suku, tingkat pendidikan dan jenis kelamin penderita TB paru dengan tingkat kepatuhan mengkonsumsi INH selama pengobatan OAT. Simpulan, INH masih sangat sensitif untuk digunakan sebagai obat lini pertama bagi penderita TB paru yang akan mulai mendapat pengobatan OAT sampai pada bulan pertama penggunaan INH.
Kata kunci: Mycobacterium tuberculosis, mutasi gen katG Ser315Thr, PCR-RFLP, Taxo urine test stripmetode Arkansas, kepatuhan
Full Text:
PDFReferences
Abe, C., I. Kobayashi, S. Mitarai, M. Wada, Y. Kawabe, T. Takashima, K. Suzuki, L-H Sng, S. Wang, H H Htay, dan H. Ogata. 2008. Biological and Molecular Characteristics of Mycobacterium tuberculosis Clinical Isolates with Low-Level Resistance to Isoniazid in Japan. J. Clin. Microbiol 46(7):2263-2268.
Ahmad, S., E. Fares, G. F. Araj, T. D. Chugh dan A. S. Mustafa. 2002. Prevalence of S315T mutation within the katG gene in isoniazid-resistant clinical Mycobacterium tuberculosis isolates from Dubai and Beirut. Int J Tuberc Lung Dis. 6(10):920-926.
Al-Hajjaj, M. S dan I. M. Al-Khatim. 2000. High rate of non-compliance with anti-tuberculosis treatment despite a retrieval system: a call for implementation of directly observed therapy in Saudi Arabia. Int J Tuberc Lung Dis. 4(4):345349.
Amin, A. G., R. Goude, L. Shi, J. Zhang, D. Chatterjee dan T. Parish. 2008. EmbA is an essential arabinosyltransferase in Mycobacterium tuberculosis. Microbiology:Society for General Microbiology Journals.154(1): 240-248.
Ananthanarayan, R dan C. K. J. Paniker. 2005. Textbook of Microbiology.7th ed. Orient Longman Private Ltd. Hiderabad.
Andina M. Deteksi Mycobacterium tuberculosis pada Sputum Penderita Tuberkulosis Paru Basil Tahan Asam Negatif dengan Reaksi Rantai Polimerase. 2012.
Becker, C., J. B. Dressman, G. L. Amidon, H.E. Junginger, S. Kopp, K.K. midha, V. P. Shah, S. Stavchansky dan D.M. Barends. 2006. Biowaiver Monographs for Immediate Release Solid Oral Dosage Forms: Isoniazid. Journal of Pharmaceutical Sciences. 96(3):522-531.
Bello, S. I dan O. A. Itiola. 2010. Drug adherence amongs tuberculosis patients in the university of Ilorin Teaching Hospital, Ilorin, Nigeria. African Journal of Pharmacy and Pharmacology. 4(3):109-144.
Bostanabad, S. Z., L. P. Titov, A. Bahrmand dan S. A. Nojoumi. 2008. Detection of mutation in isoniazid-resistant Mycobacterium tuberculosis isolates from tuberculosis patients in Belarus. Indian Journal of Medical Microbiology. 26(2):143-147.
Briken, V., S. A. Porcelli, G. S. Besra dan L. Kremer. 2004. Mycobacterial lipoarabinomannan and related lipoglycans: from biogenesis to modulation of the immune response. Molecular Microbiology. 53(2):391-403.
Brooks, G. F., K.C. Carrol, J. S. Butel, S. A. Morse. Jawetz, Melnick dan Adelberg. 2007. Medical Microbiology. 24th ed. McGraw-Hill Companies, Inc. USA.
Burman, W. J., D. L. Cohn, C. A. Rietmeijer, F. N. Judson, J. A. Sbarbaro dan R. R. Reves. 1997. Noncompliance With Directly Observed Therapy for Tuberculosis. Chest. 111:1168-1173.
Chuah SY. 1991. Factors associated with poor patient compliance with antituberculosis therapy in Northwest Perak, Malaysia. Tubercle. 72: 261-264.
Colangeli, R., V. L. Arcus, R. T. Cursons, A. Ruthe, N. Karalus, K. Coley, S. D. Manning, S. Kim, E. Marchiano dan D. Alland. 2014. Whole Genome Sequencing of Mycobacterium tuberculosis Reveals Slow Growth and Low Mutation Rates during Latent Infections in Humans.Plos One. 9(3):e91024.
Ensembl Genomes. 2015. Mycobacterium tuberculosis H37Rv. http://bacteria.ensembl.org/mycobacterium_tuberculosis_h37rv_asm195 95v2. 16 juni 2015. (15.00).
Falzon, D., E. Jaramillo, H.J. Schunemann, M. Arentz, M. Bauer, J. Bayona, L. Blanc, J.A. Caminero, C.L. Daley, C. Duncombe, C. Fitzpatrick, A. Gebhard, H. Getahun, M. Henkens, T.H. Holtz, J. Keravec, S. Keshavjee, A.J. Khan, R. Kulier, V. Leimane, C. Lienhardt, C. Lu, A. Mariandyshev, G.B.Migliori, F.Mirzayev, C.D. Mitnick, P. Nunn, G. Nwagboniwe, O. Oxlade, D. Palmero, P. Pavlinac, M.I. Quelapio, M.C. Raviglione, M.L. Rich, S. Royce, S. Rusch-Gerdes, A. Salakaia, R. Sarin, D. Sculier, F. Varaine, M. Vitoria, J.L. Walson, F. Wares, K. Weyer, R.A. White, dan M. Zignol. 2011. WHO Guidelines for The Programmatic Management of Drug-Resistant Tuberculosis: 2011 Update. European Respiratory Journal. 38(3):516-528.
FAD (Food and Drug Administration). 2013. Chemistry and Toxicology Devices, Strip Test, Isoniazid unclassified. Clinical Chemistry and Clinical Toxicology Devices Panel of the Medical Devices Advisory Committee Meeting Announcement. 25-26 April: 1-23.
Frank, J., Y. Hirsch-Moverman dan P. Colson. 2005. Adherence to treatment for latent tuberculosis infection: a manual for healthcare providers. Charles P. Felton National Tuberculosis Center. 1-54.
Gad, A., A. M. A. Mandil, A. A. R. Sherif, Z. M. Gad dan S. Sallam. 1997. Compliance with antituberculosis drugs among tuberculosis patients in Alexandria, Egypt. Eastern Mediterranean Health Journal. 3(2):244-250.
Gandhi, N. R., A. Moll, A. W. Sturm, R. Pawinski, T. Govender, U. Lalloo, K. Zeller, J. Andrews dan G. Friedland. 2006. Extensively drug-resistant tuberculosis as a cause of death in patients co-infected with tuberculosis and HIV in a rural area of South Africa. http://www.thelancet.com. 30 Februari 2014 (19:32).
Genbank. 2015. Mycobacterium tuberculosis H37Rv, complete genome. http://www.ncbi.nlm.nih.gov/nuccore/NC_000962.3?report=genbank. 16 juni 2015. (15.12).
Goude, R dan T. Parish. 2008. The genetics of cell wall biosynthesis in Mycobacterium tuberculosis. Future Microbiol. 3(3):299-313.
Guo, H., Q. Seet, S. Denkin, L. Parsons dan Y. Zhang. 2006. Molecular characterization of isoniazid-resistant clinical isolates of Mycobacterium tuberculosis from the USA. Journal of Medical Microbiology. 55:1527-1531.
Hanifa, Y., K. Mngadi, J. Lewis, K. Fielding, G. Churchyard dan A. D. Grant. 2007. Evaluation of the Arkansas method of urine testing for isoniazid in South Africa. Int J Tuberc Lung Dis. 11(11):1232-1236.
Haynes, R.B., D. W. Taylor dan D. L. Sackett. 1979. Compliance in Health Care. Baltimore, Maryland. Johns Hopkins University Press.
International Union Against Tuberculosis and Lung Disease (IUATLD). 2002. Interventions for Tuberculosis Control and Elimination. Paris.
Jin, J., G. E. Sklar, V. M. S. Oh dan S. C. Li. 2008. Factors affecting therapeutic compliance: A review from the patients perspective. Therapeutics and Clinical Risk Management. 4(1):269286.
Kardas, P dan W. R. Bishai. 2006. Compliance in anti-infective medicine. Adv Stud Med. 6(7): S652-S658.
Kementerian Kesehatan RI. 2011. Pedoman Nasional Pengendalian Tuberculosis. Direktorat Jendral Pengendalian Penyakit dan Penyehatan Lingkungan. Jakarta..
Kementerian Kesehatan RI. 2012. Modul Pelatihan Pemeriksaan Dahak Mikroskopik TB. Direktorat Jendral Pengendalian Penyakit dan Penyehatan Lingkungan. Jakarta.
Lina, M. R., B. Bela dan A. Yasmon. 2009. Deteksi mutasi gen KatG Mycobacterium tuberculosis dengan metode PCR (polymerase chain reaction) - Hibridisasi dot blot menggunakan pelacak oligonukleotida bertanda 32P. Scientific Journal for The Applications of Isotopes and Radiation. 5(1):54-67.
Lisdawati, V., I. Parwati, P. Sudarmon, T. M. Sudiro, R. Ramadhany1, N. Puspandari, L. Rifati1 dan Triyani S. 2010. Studi Pemetaan Awal DNA Mycobacterium tuberculosis complex Secara Spoligotyping Pada Hasil Isolasi Dahak Pasien Tuberkulosis Paru Dari 10 Ibu Kota Propinsi (Bagian I). Buletin Penelitian Kesehatan. 38(4):169-185.
Levy, S. B., 2002. Factors impacting on the problem of antibiotic resistance. Journal of Antimicrobial Chemoteraphy. 49:25-30.
Marahatta, S.B., S. Gautam, S. Dhital, N. Pote, A. K. Jha, R. Mahato, S. Mishra, B. H. Poudel, P. Ramasoota, J. Kaewkungwal dan P. Singhasivanon. 2011. KatG (SER 315 THR) Gene Mutation in Isoniazid Resistant Mycobacterium tuberculosis. Kathmandu Univ Med J. 9(1):19-23.
Meissner, PE., P. Musoke, A. Okwera, J. E. G. Bunn dan J. B. S. Coulter. 2002. The value of urine testing for verifying adherence to anti-tuberculosis chemotherapy in children and adults in Uganda. Int J Tuberc Lung Dis. 6(10):903908.
Mikusov, K., M. Belnov, J. Kordulkova, K. Honda, M. R. McNeil, S. Mahapatra, D. C. Crick dan P. J. Brennan. 2006. Identification of a Novel Galactosyl Transferase Involved in Biosynthesis of the Mycobacterial Cell Wall. Journal of Bacteriology. 188(18):6592-6598.
Mokrousov, I., T. Otten, M. Filipenko, A. Vyazovaya, E. Chrapov, E. Limeschenko, L. Steklova, B. Vyshnevskiy dan O. Narvskaya. 2002. Detection of Isoniazid-Resistant Mycobacterium tuberculosis Strains by a Multiplex Allele-Specific PCR Assay Targeting katG Codon 315 Variation. Journal of Clinical Microbiology. 40(7):2509-2512.
Munoz, E. B., M. F. Dorado, J. E. Guerreroc dan F. M. Martnez. 2014. The effect of an educational intervention to improve patient antibiotic adherence during dispensing in a community pharmacy. Aten Primaria. 46(7):367-375.
Musser, J. M., V. Kapur, D. L. Williams, B. N. Kreiswirth, D. V. Soolingen, dan J. D. A. van Embden. 1996. Characterization of the Catalase-Peroxidase Gene (katG) and inhA Locus in Isoniazid-Resistant and -Susceptible Strains of Mycobacterium tuberculosis by Automated DNA Sequencing: Restricted Array of Mutations Associated with Drug Resistance. The Journal of Infectious Diseases. 173:196-202.
Musser, J. M. 1995. Antimikrobial Agent Resistance in Mycobacteria: Molecular Genetic Insights. Clinical Microbiology Review. 8(4):496-514.
Naing, N. N., C. DEste, A. R. Isa, R. Salleh, N. Bakar dan M. R. Mahmod. 2001. Factors contributing to poor compliance with anti-tb treatment among tuberculosis patients. Southeast Asian J Trop Med Public Health. 32(2):369-382.
Portillo, P. D., A. Reyes, L. Salazar, M. D. C. Menendez dan M. J. Garcia. 2007. Genomics and Proteomix. Tuberculosis 2007, From Basic Science to Patient Care. www.tuberculosistextbook.com. 14 Desember 2012 (14:33).
Preziosi, P. 2007. Isoniazid: Metabolic Aspects and Toxicological Correlates. Current drug metabolism. Bentham Science Publishers Ltd .8(8):839-851.
Prianty, I. R., S. Muda dan Rasmaliah. 2012. Karakteristik penderita tuberkulosis paru pada balita yang dirawat inap di Rumah Sakit Vita Insani Pematang Siantar tahun 2010-2012. Departemen Epidemiologi FKM Universitas Sumatera Utara. Medan.
Public Health Agency of Canada. 2010. Mycobacterium tuberculosis complex: Pathogen Safety Data Sheet Infectious Substances. http://www.phac-aspc.gc.ca/lab-bio/res/psds-ftss/tuber-eng.php. 27 Oktober 2013 (22.34).
Ragheb, M. N, C. B. Ford, M. R. Chase, P. L. Lin dan J. L. Flynn. 2013. The mutation rate of mycobacterial repetitive unit loci in strains of M. tuberculosis from cynomolgus macaque infection. BMC Genomics. 14(145):1471-2164.
Ramaswamy, S dan J. M. Musser. 1998. Molecular genetic basis ofantimicrobial agent resistance in Mycobacterium tuberculosis: 1998 update. Tubercle and Lung Disease. 79(1):3-29.
Ramaswamy, S. V., R. Reich, S-J. Dou, L. Jasperse, X. Pan, A. Wanger, T. Quitugua dan E. A. Graviss. 2003. Single Nucleotide Polymorphisms in Genes Assosiated with Isoniazid Resistance in Mycobacterium tuberculosis.Antimicroba. Agents Chemother. 47(4):1241-1250.
Rattan, A., A. Kalia dan N. Ahmad. 1999. Multidrug-resistant Mycobacterium tuberculosis: molecular perspectives. Ind. J. Tub. 46(51):51-68.
Rie, A.V., R. Warren, I. Mshanga, A. M. Jordaan, G. D. Van der Spuy, M. Richardson, J. Simpson, R. P. Gie, D. A. Enarson, N. Beyers, P. D. Van Helden dan T. C. Victor. 2001. Analysis for a Limited Number of Gene Codons Can Predict Drug Resistance of Mycobacterium tuberculosis in a High-Incidence Community. J. Clin. Microbiol 39(2):636-641.
Ryan, K.J. dan C.G. Ray. 2010. Sherris Medical Microbiology. 5th ed. McGraw-Hill Companies, Inc. USA.
Sacco, E., A. S. Covarrubias, H. M. OHare, P. Carroll, N. Eynard, T. A. Jones,T. Parish, M. Daffe, K. Backbro dan A. Quemard. 2007. The missing piece of the type II fatty acid synthase system from Mycobacterium tuberculosis. Proceedings of National Academy of Sciences of the United States of America. 104(37):1462814633.
Schraufnagel, D. E., R. Stoner, E. Whiting, G. S-Torbeck dan M. J. Werhane. 1990. Testing for lsoniazid* An Evaluation of the Arkansas Method. Chest. 96(2):314-316.
Shrestha, R., R. N. Joshi1, K. Joshi, B. H. Poudel, dan B. G.Shrestha. 2011. Analysis of KatG Ser315Thr Mutation in Multidrug Resistant Mycobacterium tuberculosis and SLC11A1 Polymorphism in Multidrug Resistance Tuberculosis in Central Development Region of Nepal Using PCR?RFLP Technique: A Pilot Study. Nepal Journal of Biotechnology. 1(1):14?21.
Sihombing, H. 2011. Pola Resistensi Primer Pada Penderita TB Paru Kategori I di RSUP H. Adam Malik Medan. Tesis. Program Pendidikan Dokter Spesialis Departemen Pulmonologi & Ilmu Kedokteran Respirasi Fakultas Kedokteran Universitas Sumatera Utara. Medan.
Sjahrurachman, A. 2010. Diagnosis Multidrug Resistant Mycobacterium Tuberculosis. Jurnal Tuberkulosis Indonesia. 7(2):8-11.
Soepandi, P. Z. 2010. Diagnosis dan faktor yang mempengaruhi terjadinya TB-MDR. Jurnal Tuberkulosis Indonesia. 7(2):16-19.
Stephenson, B. J., B. H. Rowe, R. B. Haynes, W. M. Macharia dan G. Leon. 1993. Is This Patient Taking the Treatment as Prescribed?. The Journal of The American Medical Assosiation. 269(21):2779-2781.
Suswati, E. 2006. Hubungan tingkat pendidikan dengan kepatuhan minum obat pada penderita tuberkulosis paru. Pengembangan Pendidikan. 3(1):67-73.
Sweetman, S. C. 2009. Martimdale. The Complete Drug Reference. 36th ed. Pharmaceutical Press. London.
Teixeira, R. L. F., M. Q. P. Lopes, P. N. Suffys dan A. R. Santos. 2013. Tuberculosis Pharmacogenetics: State of The Art. http://dx.doi.org/10.5772/54984. 23 Oktober 2013 (20.33).
Uniprot. 2015. Catalase-peroxidase - katG - Mycobacterium tuberculosis (strain ATCC 25618 / H37Rv) Version 4. http://www.uniprot.org/uniprot/P9WIE5. 25 Juli 2015. (13.28).
Wang, J. Y., R. M. Burger dan K. Drlica. 1997. Role of Superoxide in Catalase-Peroxidase-Mediated Isoniazid Action against Mycobacteria. Antimicrob. Agents Chemother. 42(3):709-711.
Warianto, C. 2013. Mutasi. http://www.konsepbiologi.wordpress.com. 2 Mei 2014 (20.25).
World Health Organization (WHO). 2003. Adherence to long-term therapies: Evidance for action. http://www.who.int/tb/data. 23 Oktorber 2013 (13:50).
World Health Organization (WHO). 2014. Global Tuberculosis Report 2014. WHO Press. Switzerland.
World Health Organization (WHO). 2013. Definition and reporting framework for tuberculosis 2013 revision. http://www.who.int. 22 November 2012 (14:01).
World Health Organization (WHO). 2014. Tuberculosis control in the South-East Asia Region: Annual Report 2014.http://www.who.int. 22 November 2012 (15:00).
World Health Organization (WHO). 2014. Global Tuberculosis Report 2014: Drug Resistant TB Survaillence and Response. .http://www.who.int. 3 April 2015 (09:00).
Wright, G. D. 2012. Back to the future: a new old lead for tuberculosis. EMBO Mol Med. 4:1029-1031.
DOI: https://doi.org/10.30596/bf.v3i3.2066
DOI (PDF): https://doi.org/10.30596/bf.v3i3.2066.g2288
Refbacks
- There are currently no refbacks.
JURNAL BULETIN FARMATERA
Gedung Kampus 1 Universitas Muhammadiyah Sumatera Utara (UMSU) Lantai II, Laboratorium Farmakologi dan Terapi Fakultas Kedokteran UMSU Jalan Gedung Arca No. 53 Medan Sumatera Utara Indonesia, Kode Pos 20217.
Contact (WA): 0812-6208-2844
E-mail: jurnalpanduhusada@umsu.ac.id
This work is licensed under a Creative Commons Attribution-ShareAlike 4.0 International License.