1. TURKISH THORACIC SOCIETY ANTALYA APRIL, 2005 TB Drug Susceptibility Testing (DST) and Case Management Professor Michael Iseman

2. TB Drug Susceptibility Testing (DST) and Case Management The Central Questions regarding Drug Susceptibility Testing (DST) include: Why should we do DST? For which patients? How should we do DST? How do we act on the results of DST?

3. TB Drug Susceptibility Testing (DST) and Case Management Why should we do DST? To improve cure rates To lessen TB transmission in hospitals and homes To prevent further acquired drug resistance

4. TB Drug Susceptibility Testing (DST) and Case Management Why should we do DST? An illustrative case: - A 42 y.o. woman is admitted to the hospital with presumed TB - Present illness: - increasingly productive cough for 2 months - feverish, chills, night-sweats, 15# weight loss - sought care after coughing up  1 cup of red blood - Her husband died 1 year ago after 5 years treatment for TB - Her chest x-ray showed a RUL cavity with pneumonic shadows in both lower lobes - Sputum Ziehl-Neelsen smear 4+ AFB

5. TB Drug Susceptibility Testing (DST) and Case Management DST Case: Course - Treatment: The patient was started on INH/RIF/PZA and EMB - Contact investigation: 3 children in house, ages 11, 7 and 3 • All children were PPD positive • The 3 y.o. child had unilateral hilar adenopathy • All children were begun on INH preventive therapy - Because of continued hemoptysis, the patient was kept in the hospital

6. TB Drug Susceptibility Testing (DST) and Case Management DST Case: Outcome - Despite treatment with INH/RIF/PZA/EMB, patient had persistent cough, fever, hemoptysis and weight loss for 6 weeks. - Due to poor response, streptomycin and ciprofloxacin were added empirically at 6 weeks. - Despite 2 months of INH preventive therapy, the 3 y.o. develops lethargy, irritability and low grade fever; a lumbar puncture reveals CSF pleocytosis, low sugar and elevated protein.

7. TB Drug Susceptibility Testing (DST) and Case Management DST Case: Outcome - Despite adding SM and Cipro, the patient had a massive hemoptysis on hospital day #57 and died. - The 3 y.o. child was begun on INH/RIF/PZA for presumed TB meningitis but progressed to seizures and obtundation. • Sputum obtained from the patient aftertheinitial6weeks therapy was sent for DST. Five months after treatment was begun, the test finally was reported: resistant to INH, RIF, EMB and streptomycin. • Three months after the patient was admitted to the TB ward, 4 of the 11 staff caring for him converted their PPD tests to positive.

8. TB Drug Susceptibility Testing (DST) and Case Management What are the lessons from our failure to recognize MDR-TB in this case? 1. Inadequate therapy was associated with (caused) the original patient’s death. 2. Inadequate therapy was associated with progressive TB meningitis and irreversible brain damage in the 3 y.o. child. 3. Inadequate therapy of the original patient was associated with prolonged infectiousness and transmission of MDR-TB infection to 4 healthcare workers.

9. TB Drug Susceptibility Testing (DST) and Case Management How could these complications have been avoided? 1. The history of her husband’s TB treatment for 5 years and eventual death should have alerted to the risk of MDR-TB. 2. Had direct-susceptibility testing been done on the original specimen, clinicians could have been aware of the MDR-TB within 18 to 21 days and revised therapy for the original case and the 3 year old contact. 3. Had they recognized MDR-TB earlier, special steps could have been taken (negative pressure room, ultraviolet germicidal irradiation and personal respiratory protection [N95 respirators])to protect the staff from transmission.

10. TB Drug Susceptibility Testing (DST) and Case Management What should be the policy in Turkey about DST? 1. I don’t know the answer! 2. But, given the reported rates of MDR-TB in Turkey, consideration might be given to doing initial DST for INH and RIF on all new cases. 3. DST for INH and RIF can be done on solid agar (Heifets) for $2-3/specimen.