1. Acquired Drug Resistance  64 year old female of Hmong ethnicity with long standing, poorly controlled diabetes. No hx TB dx/tx.  11/6/08 CXR “active processes in both upper lobes that are most likely inflammatory in nature”  Sputa AFB smear negative  Plan was to begin empiric treatment after pulmonary consult  Referred to pulmonologist, but failed appointments, no treatment  Culture negative, no treatment

2. Acquired Drug Resistance  Aug 2009 she collapsed in her home  Arrived at hospital via ambulance, unconscious  Transferred to Doctor’s Hospital in Modesto  Reportedly had cough since the November 2008 exam  Pt reports that she is now “skinny”, implying weight loss, but none documented

3. Acquired Drug Resistance  8/29/09 - Heavily smear (+) with bilateral infiltrates on CXR  8/31/09 - Began RIPE  Initial isolate pan-sensitive  10/2/09 - EMB discontinued  11/6/09 - PZA discontinued  10/8/09 - Smears become negative  Cultures remain positive

4. Acquired Drug Resistance  1/12/10 - CXR “Progressive bilateral upper lobe infiltrates”  1/27/10 - Smears become 2+ AFB positive  Subsequently, it was learned that she had begun vomiting (start date unclear) shortly after DOT worker left each day  She did not report this for several months

7. Acquired Drug Resistance  Repeat DST results show: Resistance to INH, Rif Resistance to INH, Rif Sensitive to EMB, PZA, ETA, CM, AK & LFX Sensitive to EMB, PZA, ETA, CM, AK & LFX

9. Acquired Drug Resistance  Hospitalized & expanded regimen started: Amikacin, 750 mg 5x wk via PICC (later lowered) Amikacin, 750 mg 5x wk via PICC (later lowered) Moxifloxacin, 400 mg po qd Moxifloxacin, 400 mg po qd Ethambutol, 1200 mg po qd Ethambutol, 1200 mg po qd PZA, 1250 mg po qd PZA, 1250 mg po qd Linezolid, 600 mg po qd Linezolid, 600 mg po qd B6, 100 mg po qd B6, 100 mg po qd Zofran for vomiting Zofran for vomiting  Baseline color vision and hearing OK. Glucose levels, LFTs, and renal functions were excellent throughout hospital stay

10. Therapeutic Drug Levels (MFX collected 4/19/10, all others 4/23/10) DrugDose 2 hr level 6 hr level Ref Range EMB 1200 mg po qd 0.901.86 2 hr 2-6 mcg/ml PZA 1250 mg po qd 18.1829.53 2 hr 20-60 mcg/ml MFX 400 mg po qd 3.362.06 2 hr 3-5 mcg/ml No 6 hr range LNZ 600 mg po qd 3.537.02 2 hr 12-24 mcg/ml AK 550 mg IV 5d/wk 20.8 Cmax 35.1 7.3 Cmax 35-45 mcg/ml