Marie Turner, M.D. Jo-Ann Keegan, R.N., M.S.N. Case Presentation “and the band played on” to the tune of MDR-TB November 24 2006 Marie Turner, M.D. Jo-Ann Keegan, R.N., M.S.N.

Case Details 16 y.o. U.S.A. born student in a suburban high school Played a wind instrument in one of the largest high school bands in the state Presented with cough, fever, chest pain for more than 1 month duration CXR: RUL pneumonia TX with Quinolone x 10 days with improvement. CXR 2 weeks later: resolving pneumonia

Case Details Several weeks later symptoms returned, hospitalized – pneumonia treated with Azithromycin, transferred to a medical center for IV anti-biotics. DX at Medical CTR.: SM (+), cavitary TB D/C on 5 drugs INH, RIF, PZA, EMB and Levo. INH resistance suspected

History Student visited endemic country from age 2 – 11 months TST positive, CXR negative at age 2 Treated with INH for 1 year Sensitivities after 8 weeks treatment: Resistant to INH RIF EMB STREP

History Treatment guidelines what would you do here? Treatment INH changed to 900 mg briefly, then discontinued EMB and RIF discontinued, PZA continued LEVO changed to CIPRO then GATI due to joint symptoms CYCLO and CAPREO added

Table 1: Treatment Summary for Case Medication Duration Reason to Discontinue Isoniazid (INH) 8 weeks Organism resistant to INH 2 weeks of 900 MG dosages Rifampin (RIF) 6 weeks Organism resistant to RIF Pyrazinamide (PZA) 9 months Elevated liver function tests Asymptomatic with severe hepatitis Ethambutol (EMB) Organism resistant to EMB Levofloxacin (Levo) 1 month Joint symptoms Ciprofloxacin (Cipro) 3 weeks Physician preference – changed to Tequin Gatifloxacin (Tequin) 12 months Treatment completed – (Drug well tolerated) Cycloserine Capreomycin IM 2 months Intensive induction phase completed – Maximum dose PASER 10 months Treatment completed – Drug well tolerated

Identifying and Treating Contacts Period of infectiousness prior to diagnosis and treatment determined from symptom history School staff, parents and health care providers interviewed to determine possible school, home, social and work contacts Contacts classified into risk groups for recent exposure and previous infection Contacts interviewed to determine previous skin test status

Identifying and Treating Contacts Band members stratified by instrument type and room position. Contacts likely infected with MDR TB started on at least 2 drugs based on known susceptibility of the source case isolate. Medical consultation was from a physician with expertise in MDR TB. Contacts’ treatment and complication history tracked.

Identifying and Treating Contacts Patient remained in school while symptomatic for 2 months prior to diagnosis. Household: 2 of 3 household contacts had positive TST’s, with time of infection undetermined. Dad previous positive TST current CXR WNL, not treated. Mom current TST 25MM baseline 0MM TX with INH 900 mg twice weekly. TX options Boosting ? Conversion ? Sibling 13 y.o. (-) TST, (-) CXR (no window prophylaxis) School: 264 students and teacher contacts identified 250 (95%) completed TST’s and CXR’s.

Identifying and Treating Contacts School: 7 of 250 (3%) were TST positive. All 7 were in close physical proximity to the case 5/7 played a wind instrument in the band 2/7 were in close proximity in the classroom 4/7 had documented TST conversions All 7 had no known risk factors for previous exposure and were presumed to be newly infected with MDR TB. Drug treatment for school contacts: Treatment with 2 drugs to which organism sensitive (PZA, LEVO) Joint symptoms in 1 adult and 3 students were resolved after TEQUIN substituted for LEVO

Identify and Treating Contacts Drug treatment for school contacts: (continued) One student developed drug induced hepatitis toxicity Directly observed therapy was refused by parents but parents agreed to supervise meds Adolescents under reported adverse reactions to avoid serologic testing Table 2 summarizes drugs and treatment of MDR Latent Infection.

Table 2: School Converters – Treatment Summary for MDR Latent Infection Patient Exposure Type PPD Size Drugs Complications Drug Change Disposition # 1 Teacher 25 mm PZA, Levo Uric acid elevated (11.1) PZA, Tequin Completed Rx # 2 Band 10 mm Uric acid elevated # 3 15 mm Uric acid elevated (8.2) # 4 None # 5 Classroom # 6 12 mm Foot and joint pain with no elevation of Uric acid # 7 18 mm Admitted with acute liver failure and listed for a liver transplant until liver functions improved All TB drugs discontinued Unable to complete Rx

OTHER ISSUES Student did not return to school until nearly 2 months after diagnosis Culture conversion occurred over nine weeks after initial treatment started Student was not allowed to return to the same high school she was attending (with 6 weeks left to the school year) Fear and stigma of the disease extended to the school administration School nurse was threatened, to induce her to reveal the students identity, she refused caller

Conclusions - Discussion Contacts treated with second line drugs for MDR latent TB infection had clinically significant variations in adverse reactions to quinolones Source case transmission of MDR TB was extended by missed diagnosis and subsequent treatment with a quinolone for suspected community acquired pneumonia

Conclusions - Discussion Patient and family education regarding the importance of stopping medications, if adverse reactions suspected, is vital to health and treatment outcome Contacts treated with second line drugs for MDR TB require close monitoring, including serologic testing and DOT.

Conclusions - Discussion Directly Observed Therapy of MDR TB contacts would likely enhance clinical follow-up. Although parents refused this option, more education and a comprehensive effort on the part of all providers would most likely be needed to reverse this decision. Another benefit of DOT is the possible prevention of further drug resistance. Further research is necessary to address the complexities and duration of treatment for MDR latent TB infection.