Disertasi

Hubungan konsentrasi rifampisin darah dengan respons pengobatan berdasarkan hasil biakan kuman mycobacterium tuberculosis pada pasien TB paru yang diobati dengan kombinasi dosis tetap (KDT). = Association between plasma rifampisin concentration and treatment response in pulmonary TB patients treated with fixed-dosed combination regimen (FDC) based on culture of myobacterium tuberculosis.

Latar belakang. Beberapa penelitian tentang pengaruh kadar Rifampisin terhadap hasil pengobatan menunjukkan hasil yang masih kontroversial. Namun dari beberapa penelitian tersebut hanya Chang dkk. yang meneliti hubungan konsentrasi Rifampisin dengan respons terapi dan membandingkan antara kelompok respons lambat dengan respons baik. Tujuan. Penelitian ini dilakukan untuk menilai pengaruh konsentrasi Rifampisin di plasma terhadap keberhasilan pengobatan yang dilihat dari hasil biakan pada minggu ke -4 dan ke-8. Metode. Penelitian ini adalah studi analitik dengan desain kohort retrospectif membandingkan kelompok terpajan dengan kelompok tidak terpajan. Kelompok terpajan adalah subjek yang nilai konsentrasi rifampisin di dalam plasma > 8 mg/dL, sedangkan kelompok tidak terpajan adalah subjek yang nilai konsentrasi rifampisin di dalam plasma < 8 mg/dL. Pada masing-masing kelompok dilakukan pengu- kuran konsentrasi rifampisin pada plasma dan dilihat hubungannya dengan respons bakteriologik berdasarkan pemeriksaan biakan pada minggu ke-4 serta dinilai faktor yang memengaruhi. Hasil : Jumlah subjek yang direkrut dalam penelitian ini adalah 217 orang, 126 orang laki-laki (62,7 %) berbanding 75 orang perempuan (37,3 %). Rerata kadar rifampisin yang diperoleh yaitu 8,184 mg/dL dengan jumlah yang masuk kategori konsentrasi rifampisin terapeutik yaitu 90 subjek (45,9 %) berbanding dengan subterapeutik yaitu 87 subjek (44,4 %). Dari hasil pemeriksaan kultur, yang masuk kategori respons cepat (kultur tidak tumbuh pada minggu ke-4) 111 subjek (66,5 %) dan kategori respons lambat 56 subjek (33,5 %). Dari hasil analisis didapatkan hubungan yang berrnakna antara respons pengobatan dengan virulensi (p = 0,016 dengan Risk Ratio 1,83 [95% Cl : 1,08-3,11]) dan lesi foto toraks (p = 0,015 dengan Risk Ratio 1,73 [95% Cl : 1,09-2,74]). Simpulan: Penelitian ini membuktikan bahwa pemeriksaan kadar Rifampisin saja tidak bisa berperan untuk melihat respons pengobatan pada pasien TB.
Kata kunci : Konsentrasi rifampisin, respons terapi, TB.



Background: Several studies have shown controversial results regarding the effect of rifampicin concentration on treatment response. However, among those studies, only the study conducted by Chang et al. had evaluated the association between rifampicin concentration and treatment response as well as developed comparison between the slow and rapid response groups. Objective: Our study was conducted to evaluate the association between plasma rifampicin concentration and successful treatment response based on the results of culture isolates in the 4th and 8th week of treatment. Material and Method: The study was an analytical study using cohort prospective design, which compared the exposure group (individuals treated with therapeutic concentration of rifampicin) and non-exposure group (individuals treated with sub- therapeutic concentration). The exposure group was subjects with plasma rifampicin concentration > 8 mg/dL; while the non-exposure group included subjects with plasma rifampicin concentration < 8 mg/dL. Subjects were tuberculosis (TB) patients with positive results of sputum smear. Measurement of plasma rifampicin concentration was performed for all subjects, and its association with bacteriological response was evaluated based on the results of culture isolates at 4 weeks after treatment. Other affecting factors were also evaluated. Ten subjects were also analyzed to obtain a full pharmacokinetic curve for rifampicin. Result: A total of 217 subjects were recruited in our study. Among them, 126 (62.7 %) subjects were male and 75 (37.3 %) subjects were female. Mean value of rifampicin concentration was 8.184 mg/dL, with 90 (45.9 %) subjects had rifampicin therapeutical concentration and 87 (44.4 %) subjects had sub- therapeutical concentration. The culture revealed that 111 (66.5 %) subjects were categorized into rapid response group (negative results of culture in the 4th week); while 56 (33.5 %) subjects were in the slow response category. The analysis found that there was significant correlation between treatment response and virulence (p = 0.016; risk ratio 1.83[95% Cl: 1.08-3.11]). It also found significant association between treatment response and chest X-ray lesion (p = 0.015; risk ratio 1.73 [95% Cl: 1.09-2.74]). Summary: Our study has provided evidences that the assessment of rifampicin concentration alone is not useful for evaluating the response to treatment in TB patients.
Keywords: Rifampicin concentration, treatment response, TB.