Acquired Resistance to Isoniazid During Isoniazid Monotherapy in a Subject with Latent Infection Following Household Rifampicin-Resistant Tuberculosis Contact: A Case Report

Tsung-Lun Li,1 Tai-Hua Chan,2 Cheng-Hui Wang,3– 5 Ruwen Jou,2,6 Ming-Chih Yu,1,3,7 Denise Utami Putri,3,* Chih-Hsin Lee,1,3,8,* Yi-Hsien Lin3 1Department of Internal Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 2Taiwan Centers for Disease Control, Taipei, Taiwan; 3Pulmonary Research Center, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 4Department of Laboratory Medicine, Wanfang Hospital, Taipei Medical University, Taipei, Taiwan; 5School of Medical Laboratory Science and Biotechnology, College of Medical Science and Technology, Taipei Medical University, Taipei, Taiwan; 6Institute of Microbiology and Immunology, National Yang-Ming Chiao Tung University, Taipei, Taiwan; 7Schools of Respiratory Therapy, College of Medicine, Taipei Medical University, Taipei, Taiwan; 8Division of Pulmonary Medicine, Department of Internal Medicine, School of Medicine, College of Medicine, Taipei Medical University, Taipei, Taiwan*These authors contributed equally to this workCorrespondence: Chih-Hsin Lee; Denise Utami PutriPulmonary Research Center, Wanfang Hospital, Taipei Medical University, 111 Sec. 3, Xinglong Road Wenshan District, Taipei, 116, TaiwanTel +886-2930-7930Email chleetw@tmu.edu.tw; 108336@w.tmu.edu.twAbstract: Appropriate treatment is the key element in eliminating tuberculosis (TB), and requires prompt diagnosis. We presented a case of a household contact of rifampicin-resistant TB revealing reactive IFN-gamma release assay with unsuspicious clinical and radiologic examinations. She was diagnosed with latent tuberculosis infection (LTBI) and treated with isoniazid monotherapy. On the ninth month, she developed a progressive cough and was found to harbor active TB disease with added resistance to isoniazid. An individualized anti-TB regimen consisting of moxifloxacin, kanamycin, prothionamide, ethambutol, and pyrazinamide was prescribed for 20 months, leading to sputum culture conversion and improvement of the reported symptom. No recurrence was observed on one-year follow-up. Assuming high compliance to therapy, we propose that the patient may have been underdiagnosed and received sub-optimal treatment leading to acquired-drug resistance. Conventional diagnosis methods based on immunological assay and radiographical findings may be insufficient to distinguish the incipient and subclinical states of TB from LTBI.Keywords: latent tuberculosis infection, LTBI, treatment, acquired drug resistance, drug-resistant TB, subclinical TB, case report