Acquired Drug ResistanceAcquired Drug Resistance

64 year old female of Hmong ethnicity with long 64 year old female of Hmong ethnicity with long standing, poorly controlled diabetes. No hx TB standing, poorly controlled diabetes. No hx TB dx/tx.dx/tx.

11/6/08 CXR “active processes in both upper 11/6/08 CXR “active processes in both upper lobes that are most likely inflammatory in nature”lobes that are most likely inflammatory in nature”

Sputa AFB smear negativeSputa AFB smear negative Plan was to begin empiric treatment after Plan was to begin empiric treatment after

pulmonary consultpulmonary consult Referred to pulmonologist, but failed Referred to pulmonologist, but failed

appointments, no treatmentappointments, no treatment Culture negative, no treatmentCulture negative, no treatment

Acquired Drug ResistanceAcquired Drug Resistance

Aug 2009 she collapsed in her homeAug 2009 she collapsed in her home Arrived at hospital via ambulance, unconsciousArrived at hospital via ambulance, unconscious Transferred to Doctor’s Hospital in ModestoTransferred to Doctor’s Hospital in Modesto Reportedly had cough since the November 2008 Reportedly had cough since the November 2008

examexam Pt reports that she is now “skinny”, implying Pt reports that she is now “skinny”, implying

weight loss, but none documentedweight loss, but none documented

Acquired Drug ResistanceAcquired Drug Resistance

8/29/09 - Heavily smear (+) with bilateral 8/29/09 - Heavily smear (+) with bilateral infiltrates on CXRinfiltrates on CXR

8/31/09 - Began RIPE8/31/09 - Began RIPE Initial isolate Initial isolate pan-sensitivepan-sensitive 10/2/09 - EMB discontinued 10/2/09 - EMB discontinued 11/6/09 - PZA discontinued11/6/09 - PZA discontinued 10/8/09 - Smears become negative10/8/09 - Smears become negative Cultures remain positiveCultures remain positive

Acquired Drug ResistanceAcquired Drug Resistance

1/12/10 - CXR “Progressive bilateral upper 1/12/10 - CXR “Progressive bilateral upper lobe infiltrates”lobe infiltrates”

1/27/10 - Smears become 2+ AFB positive1/27/10 - Smears become 2+ AFB positive Subsequently, it was learned that she had Subsequently, it was learned that she had

begun vomiting (start date unclear) shortly begun vomiting (start date unclear) shortly after DOT worker left each day after DOT worker left each day

She did not report this for several monthsShe did not report this for several months

Acquired Drug ResistanceAcquired Drug Resistance

Repeat DST results show:Repeat DST results show: Resistance to INH, RifResistance to INH, Rif Sensitive to EMB, PZA, ETA, CM, AK & LFXSensitive to EMB, PZA, ETA, CM, AK & LFX

Acquired Drug ResistanceAcquired Drug Resistance

Hospitalized & expanded regimen started: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 qdMoxifloxacin, 400 mg po qd Ethambutol, 1200 mg po qdEthambutol, 1200 mg po qd PZA, 1250 mg po qdPZA, 1250 mg po qd Linezolid, 600 mg po qdLinezolid, 600 mg po qd B6, 100 mg po qdB6, 100 mg po qd Zofran for vomitingZofran for vomiting

Baseline color vision and hearing OK. Glucose levels, Baseline color vision and hearing OK. Glucose levels, LFTs, and renal functions were excellent throughout LFTs, and renal functions were excellent throughout hospital stayhospital stay

Therapeutic Drug LevelsTherapeutic Drug Levels(MFX collected 4/19/10, all others 4/23/10)(MFX collected 4/19/10, all others 4/23/10)

DrugDrug DoseDose 2 hr 2 hr levellevel

6 hr 6 hr levellevel

Ref RangeRef Range

EMBEMB 1200 mg 1200 mg po qdpo qd

0.900.90 1.861.86 2 hr 2-6 mcg/ml2 hr 2-6 mcg/ml

PZAPZA 1250 mg1250 mg

po qdpo qd18.1818.18 29.5329.53 2 hr 20-60 mcg/ml2 hr 20-60 mcg/ml

MFXMFX 400 mg 400 mg po qdpo qd

3.363.36 2.062.06 2 hr 3-5 mcg/ml2 hr 3-5 mcg/ml

No 6 hr rangeNo 6 hr range

LNZLNZ 600 mg 600 mg po qdpo qd

3.533.53 7.027.02 2 hr 12-24 mcg/ml2 hr 12-24 mcg/ml

AKAK 550 mg 550 mg IV 5d/wkIV 5d/wk

20.820.8Cmax Cmax 35.135.1

7.37.3 CmaxCmax 35-45 mcg/ml35-45 mcg/ml