This drug-related adverse reaction to Prothionamide happened in a 23-year-old patient diagnosed with disseminated DRTB involving the central nervous system (CNS) and lymph nodes and put on a second-line anti-TB (tuberculosis) regimen. He was diagnosed with pulmonary TB a year before and was on anti-TB for 6 months. After treatment completion, his illness was cured. But after 8 months, he began to have headaches, recurrent tonic-clonic seizures, anorexia, fever, and cervical lymphadenopathy. He had a 4 by 3 mm ring-enhancing lesion in the left partial lobe detected from brain magnetic resonance imaging (MRI). Sample taken from the lymph node by fine-needle aspiration cytology (FNAC) was positive for rifampicin-resistant Mycobacterium tuberculosis.
Disseminated DRTB involving lymph nodes and brain was diagnosed based on the FNAC and CT (computed tomography) scan results. Then, after a multidisciplinary team discussion, long-term oral regimens (i.e. bedaquiline, levofloxacin, clofazimine, linezolid, and cycloserine) were started. Along with the anti-TB drug, the patient had been on valproic acid for seizure control. The treatment was started while he was at All Africa Leprosy Rehabilitation and Training Center (ALERT) hospital, but the patient was transferred to Mizan-Tepi University Teaching Hospital (MTUTH) after 1 month of treatment follow-up. He had been treated as an inpatient at ALERT hospital and as an outpatient with monthly follow-up after being transferred to MTUTH. In his fourth month of follow-up, he developed QT prolongation (QTc 495 ms) on electrocardiography (ECG) done for routine adverse drug effect monitoring. After checking electrolytes, drug (bedaquiline)-induced QT prolongation was considered, and his treatment regimen was revised by substituting Prothionamide in place of bedaquiline, but the remaining four second-line anti-TB drugs (i.e. levofloxacin, clofazimine, linezolid, and cycloserine).
Prothionamide was discontinued about 14 days after he started taking it following the development of acute renal failure. By reviewing the clinical symptom and laboratory results done from serum and urine samples, AIN secondary to Prothionamide was diagnosed. During this time, renal failure was suspected due to Prothionamide-induced AIN and the multidisciplinary team decided to stop it. But at his fourth visit, that is before Prothionamide was initiated, renal function test, liver function test. Urinalysis and complete blood count were normal except for the ECG, which showed mild QT prolongation. Prothionamide was started at 750 mg/day. AIN was considered on that day the patient comes to the hospital after he complains of feeling fatigability, rash, and intermittent fever. On examination, he had tachycardia (105 beats per minute) and fever (37.7 C), but the blood pressure was normal (120/70 mm Hg). He had an itchy maculopapular rash around the buttocks and trunk area. From the urine dipstick test done, trace protein-positive results were detected. On urine microscopy, white blood cell count of 15 cells per high-power field (HPF), eosinophil 7 HPF, and 2 red blood cells. Urine cultures taken from the catheter showed no growth. Blood biochemistry showed that erythrocyte sedimentation rate (ESR) was 52 mm/h, C-reactive protein (CRP) was 121 mg/L, creatinine was 2.1 mg/dL, blood urea nitrogen (BUN) was 15 mg/dL, and an estimated glomerular filtration rate (GFR) was 52 mL/min/1.73 m2. The biochemistry results which came after day 11 of Prothionamide discontinuation showed that creatinine was 1.1 mg/dL and ESR was 41 mm/h. But after 16 days of Prothionamide discontinuation, renal function, ESR, and urinalysis returned to normal. The RFT (Renal function test) remained to be normal throughout treatment completion. To rule out other causes of AIN, he was asked to take drugs like beta-lactams, sulfonamides, macrolides, chloramphenicol, antiviral, nonsteroidal treatment, proton pump inhibitor, H2-receptor blockers, 5-aminosalicylates, diuretic, but he answered no. He was tested negative for infections that can precipitate AIN like HIV (human immunodeficiency virus), HBV (hepatitis B virus), HCV (hepatitis C virus), and malaria. He was also not taking the herbal medication.