Delayed Culture Conversion, Low Serum Drug Levels

September 2007

Case History

Our patient is a 54 year-old male who presented to his physician for follow up of a right upper lobe carcinoma which was ressected in 1979. He complained of shortness of breath, weight loss, fatigue, chest pain and a productive cough but no hemoptysis. A chest x-ray on June 20, 2006 revealed new bilateral alveolar infiltrates. He was referred to a pulmonologist and admitted to his hometown hospital on June 20, 2006. Smears were positive for acid fast bacilli and a CT scan June 22nd showed cavitation in the left upper lobe, bilateral infiltrates and mediastinal adenopathy. He was placed on anti-tuberculosis therapy—isoniazid (INH) 300 mgs, rifampin (RIF) 600 mgs, pyrazinamide (PZA) 1500 mgs and ethambutol (EMB) 1600 mgs daily with vitamin B6 50 mgs. Directly Observed Therapy (DOT) was started on July 7, 2006; given Monday through Friday with self-administration on the weekends. His culture grew Mycobacterium tuberculosis and was susceptible to INH, RIF and EMB.

The patient's past history included long term tobacco and alcohol abuse. He reported marijuana use in the past but denied intravenous drug abuse. He received medical disability since his lung resection in 1979. He had chronic obstructive pulmonary disease (COPD). He also was positive for Hepatitis C.

His PZA and EMB were discontinued on August 31, 2006 at the normal 2 month mark. The patient's sputum smears and cultures remained consistently positive through September 15, 2006. His sputum cultures remained positive for pansensitive pulmonary TB. While there was slight clinical improvement, the positive cultures nearly 4 months into therapy made him a possible treatment failure. He was referred to the Texas Center for Infectious Disease (TCID) for evaluation and management.

He was admitted to TCID on November 21, 2006. He weighed 149 pounds (5'9"), blood pressure was 177/100, respirations were 26 and irregular, and his pulse was 99. His films showed a stable right upper lobe nodular opacity compatible with tuberculosis. His laboratory findings on admission were: WBC 10.4, hemoglobin 12.9, hematocrit 40.4, platelets 271, metabolic panel was normal except for an albumin of 3.5. Urinalysis was significant for positive nitrate and trace leucocytes however no WBC were seen and there was no growth at 48 hours. Serum INH level was low at 1.29 (3-6 adequate) on 300 mg per day and serum RIF was low at 4.29 (8-24 adequate) on 600 mg per day.

The patient's treatment at TCID was augmented with reinstitution of PZA, EMB, and additional treatment with levofloxacin and amikacin. These were continued for 4 weeks. Based on the low serum levels, INH was increased to 600 mg and RIF was increased to 900 mg daily. His course at TCID was unremarkable; his last positive culture was obtained October 5, 2006. This isolate remained susceptible to all drugs. His sputum cultures converted to negative as of October 7, 2007 although his sputum smears remained AFB positive (less than 1 organism per field) through April 4, 2007. His LFTs remained stable throughout treatment.

The patient was discharged December 18, 2006 back to his home with DOT Monday through Friday and self-administered therapy on the weekends to completion of 6 months post-culture negativity. Patient completed DOT on April 19, 2007.

Teaching Points

Treatment Failure

Never add a single drug to a failing regimen

Tobacco abuse and TB

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Bates, M. N. et al. Risk of TB from Exposure to Tobacco Smoke: A systemic review and meta-analysis [Review Article]. Archives of Internal Medicine. Vol 167(4), 26 Feb 2007 pp. 335-342.

CDC. Treatment of Tuberculosis. Morbidity and Mortality Weekly Report. June 20, 2003. Vol 52 (RR11); pp. 1-77.

Khan, A. E. and Kimerling, M. E. "Chemotherapy of Tuberculosis" in Tuberculosis and Nontuberculous Mycobacterial Infections, Fifth Edition. Schlossberg, D., editor. McGraw-Hill, Medical Publishing Division. 2006. p. 87

Pendakar, M. S. et al. Prospective study of smoking and TB in India. Preventive Medicine. Vol 44(6), June 2007 pp. 496-498.

Heartland National TB Center
2303 SE Military Drive
San Antonio, Texas 78223
Phone: 1 (800) TEX-LUNG
Fax: (210) 531-4590