A 59-year-old Indonesian man was first diagnosed with pulmonary tuberculosis (TB) in 2011, he completed a full course of category 1 treatment of 2RHZE/4RH (rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E)) and was considered cured. In January 2018 he experienced chronic productive cough with night sweats. His physical examination was unremarkable. His initial sputum GeneXpert showed drug-susceptible Mycobacterium tuberculosis. Chest x-ray was performed, showing perihilar lung infiltrates (Figure 1). He was treated with category 2 treatment of 2RHZES/1RHZE/5RH (rifampicin (R), isoniazid (H), pyrazinamide (Z), ethambutol (E), streptomycin (S)). On the fourth month of treatment, his GeneXpert evaluation showed rifampicin resistant (RR) and was referred to an Indonesian tertiary-care hospital for initiation of MDR-TB treatment.
Choosing the appropriate MDR regiment for this patient was challenging due to his multiple comorbidities, namely: untreated chronic hepatitis B, which developed into decompensated liver cirrhosis (he was diagnosed with hepatitis B in 2011 but only began treatment with tenofovir disoproxil fumarate 300 mg q.d in January 2018); type 2 diabetes (treated with insulin); diabetic retinopathy; and osteoarthritis of right knee. Second-line injectable drugs (SLID) and ethambutol were used in his previous regimens, thus were omitted. Pyrazinamide, ethionamide/prothionamide, and p-aminosalicylic acid (PAS) were omitted due to liver cirrhosis. At the time of his MDR treatment initiation, the 2018 World Health Organization (WHO) guideline was not yet published, thus his MDR regimen was designed based on the 2016 WHO guideline. He started his MDR treatment in July 2018 (baseline body weight: 60 kg), which included levofloxacin 875 mg OD, cycloserine 875 mg OD, bedaquiline 400 mg OD for 2 weeks followed by 200 mg OD until the sixth month of treatment, linezolid 600 mg OD, isoniazid 600 mg OD, and pyridoxine 200 mg OD. Monitoring of adverse drug reaction was performed every 2-4 weeks throughout treatment period, which consisted of, but not limited to: symptom recording, routine physical examination, retinal examination, ECG, complete blood count, liver transaminase levels, bilirubin level, and renal function test. On the second month of treatment, he developed thrombocytopenia without bleeding manifestation due to linezolid-induced myelosuppression. Linezolid was stopped for 2 weeks and his platelet count increased from 36,000/microL to 90,000/microL. Linezolid was reintroduced with lower dose of 300 mg OD. On the seventh month of treatment, he developed severe depression with visual hallucination, which improved after the addition of risperidone 1 mg BID and dose reduction of cycloserine from 875 mg to 500 mg OD. On the 10th month of treatment, he developed pancytopenia due to linezolid-induced myelosuppression. Linezolid was postponed for 2 weeks and reinitiated after resolution of pancytopenia. On the 14th month of treatment, he experienced partial vision loss which was later diagnosed as linezolid-induced optic neuritis. Linezolid was substituted with clofazimine 100 mg OD. Clofazimine was considered as the best option because during this period the 2018 WHO guideline was published and reclassified clofazimine as group B medication (previously as group C medication in 2016 guideline). Since the 14th month of treatment, the regimen of levofloxacin 875 mg OD, cycloserine 500 mg OD, clofazimine 100 mg OD, isoniazid 600 mg OD, and pyridoxine 200 mg OD was maintained until the end of treatment with minimal side effect. He was considered cured after 3 separate negative sputum culture results with total treatment duration of 26 months. Sputum culture and drug susceptibility testing was performed in a government-run out of hospital laboratory. We were unable to receive on time culture result due to technical problems faced by the local laboratory which resulted in the longer treatment duration than the recommended 18-24 months. His complete treatment timeline is sumarized in Figure 2.