GENOTIP DAN RESISTENSI OBAT ANTI TUBERKULOSIS (OAT) ISOLAT Mycobacterium tuberculosis PADA KASUS TUBERKULOSIS YANG BELUM DITERAPI OAT

MARIA SILVIA MERRY, Dr. Ning Rintiswati, M. Kes ; dr Yanri Wijayanti S., PhD, SpPD, KPTI

2013 | Tesis | S2 Ilmu Kedokteran Tropis

Latar Belakang: Tuberkulosis masih merupakan masalah kesehatan yang penting untuk dikendalikan secara global. Di Indonesia insidensi kasus TB tahun 2011 sekitar 809.592 dengan angka kematian tinggi. Munculnya resistensi OAT membuat beban ganda penanggulangan penyakit ini. Resistensi OAT disebabkan beberapa hal salah satunya adalah sifat alami, mutasi, dan variasi genotip. Di wilayah Jogjakarta kemungkinan telah terjadi juga kejadian resistensi terhadap OAT tetapi hubungan resistensi dan genotip M. tuberculosis belum pernah diteliti. Tujuan: Penelitian ini bertujuan untuk melihat gambaran resistensi OAT, genotip M. tuberculosis di wilayah Jogjakarta, dan mengetahui hubungan antara resistensi OAT dan genotip M. tuberculosis. Metode Penelitian: Metode penelitian adalah potong lintang dan deskripsi analitis. Sampel adalah isolat klinis yang tidak mendapatkan terapi OAT sebelumnya koleksi Laboratorium Mikrobiologi FK UGM yang didapat dari BP4 Minggiran dan Kotagede periode Juni – Desember 2010. Uji kepekaan OAT dilakukan terhadap Isoniazid, Rifampicin, dan Streptomisin menggunakan metode proporsional LJ, sedangkan genotyping dengan menggunakan Spoligotyping berbasis PCR dengan primer Dra dan Drb. Pengolahan data pola resistensi dan pola genotip berupa deskripsi, sedangkan analisis hubungan pola resistensi OAT dengan pola genotip menggunakan chi square. Hasil Penelitian: Didapatkan 33 sampel yang dilakukan uji kepekaan kuman dengan hasil 17 isolat (51,52%) sensitif terhadap INH, RIF, STREP, dan 16 isolat (48,48%) resisten terhadap satu atau lebih OAT. Monoresisten didapatkan pada 12 isolat (36,36%), poliresisten non MDR pada 3 isolat(9,09%), dan MDR didapatkan pada 1 isolat (3,03%). Pola genotip menggambarkan 10 isolat (30%) adalah galur Beijing dan 23 isolat (70%) adalah Non Beijing dengan variasi EAI, LAM, U, Harleem, T, Manu, dan Miscellaneous dengan dominasi EAI (9-14%). Hasil analisis chi square p=0,034 (p<0,05), ratio prevalence 2,96 (95 CI 0,26 – 0,57) Simpulan: Hasil penelitian ini menunjukkan bahwa jumlah isolat M. tuberculosis yang sensitif dan resisten terhadap OAT adalah sama. Resistensi yang didapatkan dalam penelitian dominan monoresisten. Galur Beijing cenderung berisiko terhadap resistensi OAT 2,96 kali lebih besar dibanding galur Non Beijing.

Background: Tuberculosis (TB) is still a prominent health problem which needs to be controlled worldwide. In Indonesia, the incidences of TB cases in 2011 were 809,592 with a high mortality rate. The emergence of mycobacterium’s resistance against Oral Anti-Tuberculosis (OAT) gives a double burden for prevention of the disease. This resistance against OAT is caused by several things, one of which is the nature of mycobacterium, mutations and genotype strain variation. It is likely to have occurred in the Jogjakarta area as well, but the incidences of resistance to the relationship of OAT resistance and M. tuberculosis genotype have not been studied. Objective: This study is aimed to get a description of OAT’s resistance result and the genotype of M. tuberculosis in Jogjakarta area, as well as determined the correlation between M. tuberculosis’ genotypes and resistance against OAT resistancy. Methods: The methods of research were cross-sectional and analytical descriptions. Samples used in this research were isolated clinically, which were taken from patients who hadn’t received OAT therapy before the sample collection at the Faculty’s Laboratory of Microbiology. Patients were recruited from BP4 (Balai Pengobatan Penyakit Paru = Health Center for Lung’s Diseases) at Minggiran and Kotagede area, for the period of June 2010 - December 2010. Sensitivity test for OAT were done for Isoniazid, Rifampicin and Streptomycin, using LJ’s proportion method, whereas for genotyping, we were using PCR-based Spoligotyping, with Dra and DRB primers. Data processing for genotypes and resistance result were in descriptive form, while the analysis of the OAT resistance and genotypes’ correlation were using chi square. Results: From 33 samples which were collected and tested for sensitivity, 17 isolates (51.52%) were sensitive to INH, RIF, STREP, ETAM and 16 isolates (48.48%) were resistant to one or more of OAT. Mono resistant was shown in 12 isolates (36.36%), poly resistant non MDR 3 isolates (9.09%), and MDR isolates obtained in 1 (3.03%). The description of Genotype patterns are 10 isolates (30%) were Beijing strains and 23 isolates (70%) were non-Beijing with a variety of EAI, LAM, U, Harleem, T, Manu, and Miscellaneous. The dominance Non Beijing strain is EAI (9-14%). The chi square’s analysis are p = 0.034 (p <0.05), prevalence ratio of 2.96 (95 CI 0.26 to 0.57) Conclusion: Results of this study indicate that the numbers of M. tuberculosis sensitive and resistant to OAT isolates are the same. Resistance obtained in the study is mono resistant dominant. The Beijing strains tend to be at risk for OAT resistance 2.96 times more than the non-Beijing strains.

Kata Kunci : resistensi OAT, genotip, M. tuberculosis, spoligotyping