INTRODUCTION:Failure to respond to tuberculosis (TB) treatment is generally the result of drug resistance or poor compliance with therapy. Less commonly, it is due to subtherapeutic blood levels of antituberculosis drugs. We describe a patient where subtherapeutic blood levels of antituberculosis drugs led to initial failure of TB therapy.
CASE PRESENTATION:A 55 yr old male was diagnosed with bilateral upper lobe cavitary pulmonary TB with numerous Acid Fast Bacilli (AFB) in sputum and was started on standard doses of Isoniazid (INH), Rifampin (RIF), Ethambutol (EMB) and Pyrazinamide (PZA). Patient remained 4+ AFB smears positive for over 4 weeks without adequate clinical response despite pansensitive TB organism. He was directly observed in hospital with treatment compliance. Therefore, the possibility of subtherapeutic blood levels was suspected. Investigations for malabsorption including stool for fat, ova and parasites, serum B12 level, antigliadin and antiendomyseal (Transglutaminase) antibodies were all negative. CAT scan of abdomen with oral and intravenous contrast showed calcified granulomas in the spleen and minimal nodular hyperplasia of adrenal glands. There was no evidence of intestinal pathology. Initial peak blood levels of INH, RIF, EMB and PZA performed two hours after ingestion on empty stomach were subtherapeutic. Therapeutic blood levels were not achieved despite INH 600 mg and RIF 900 mg orally daily and therefore patient was treated with parenteral INH 300 mg, RIF 600 mg, Levaquin and Capreomycin and oral EMB 1600 mg and PZA 2500 mg daily. With multiple dose adjustments based on repeated blood levels, therapeutic drug levels were achieved four weeks later during which sputum cultures became negative for tuberculosis. Patient was discharged after around 5 months of in-patient therapy. Nine months of therapy with therapeutic levels completed while patient was on INH 600 mg and RIF 900 mg orally daily (higher than standard dose).
DISCUSSIONS:Tuberculosis is a readily curable disease when adequate antituberculous therapy is properly administered. Short-course chemotherapy on standard doses of INH, RIF, and PZA are associated with 95% cure rates if patient is compliant and the organism is pansensitive. Administration of medications through directly observed therapy (DOT) assures patient‘s adherence to treatment. Subtherapeutic blood levels must be suspected when all the above are in place and patient is not improving. Subtherapeutic blood levels have been seen in patients with HIV disease and when there is a malabsorption state. In these patients, drug dosing should be dictated by earlier blood levels.
CONCLUSION:Candidates for early blood level testing of anti-TB drugs include patients not responding to treatment in a setting of a pansensitive organism and compliance with therapy specially in patients with AIDS or a malabsorption state. It is possible that TB enteritis contributed to subtherapeutic blood levels in our patient as more therapeutic levels were seen once patient showed clinical improvement.
DISCLOSURE:Muhammad Rehman, No Financial Disclosure Information; No Product/Research Disclosure Information