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TB Grand Rounds

Complicated Multiple Drug Resistant Tuberculosis Case

Ed Zuroweste, MDChief Medical Officer

Migrant Clinicians NetworkDecember 5, 2006

Speaker: Edward Zuroweste, MD

Medical Director of the Migrant Clinicians Network, Inc.Assistant Professor of Medicine at Johns Hopkins School of Medicine– Directs International Health Elective in Honduras for

4th year medical studentsAttending physician for Franklin and Dauphin County Pennsylvania State Health Department Tuberculosis ClinicConsultant for Bureau of Primary Health Care

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Objectives

Discuss cultural issues dealing with a complex tuberculosis case

Discuss the availability and use of Regional TB Center in assisting in the treatment of complicated tuberculosis cases

Identify different perspectives and alternative resources for the resolution of challenging cases

Patient History

Patient is a 41-yr- old Chinese male who emigrated to US in July 1989Father had dx of M.tb in 1957, treated with rest/nutrition in China; reactivated TB in 1989, Rx with 3-4 drugs1989 - Patient infected by father, CXR abnormal; c/o cough/fever/weight loss; treated with 3-4 drugs self admin.; 4 months in China then 2-3 months in US 1989

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Current Medical History

Routine PE by FMD in March 2005 CXR—abnormal with RUL infiltrate/volume loss Patient totally asymptomatic for active TB4/05 seen Hershey Med. Ctr. Infect. Disease clinic 3 AFB negative smears – 4/29, 5/5 & 5/6/05 Patient leaves for extended business trip to China 5/9/05!!!

Past Medical History

Patient suspected Hepatitis B in 1980s (pos. core/surface Hep. B antibody)HIV negativeNo other chronic diseasesNo chronic medicationsNo allergiesNo alcoholismNo smoking

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Social/Work History

Patient born in China moved to US 7/89 Married----wife born in China Sons ages 7 and 12 years; born in US Patient employed local industry --- die technician frequent trips to China for workWorks first and second shifts4/25/05 business trip/flew to North Carolina5/9/05 left for China

Physical Exam

Vitals: Afebrile, P 70, RR 12, BP 110/70Height 5’ 8” Weight 146

Pertinent physical findings:Gen: Well appearing Chinese male, NADNeck: No lymphadenopathyLungs: clear except for few rales/rhonchi RULHeart: without murmur RSRAbd: without hepatosplenomegaly

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Initial Laboratory Results Critical Clinical Information

On 5/29/05 report on the 4/29/05 specimen was M.tb culture pos (Pt still in China)6/3/05 – TST result for wife 16mm, CXR NAD; refuses LTBI RxTST result for both sons 00mm (repeat TST on 1/10/06 still 00mm for both sons)6/17/05 – PA BOL report drug resistance to INH/EMB/SM/RIF/PZA (Pt still in China)6/28/05 – additional resistance to Kanamycin; Ethionaminde; Capreomycin; sensitive to Cycloserine (Pt still in China)

Clinical Course (1)

6/21-24/05 – Pt hospitalized in Shanghai with r/o pneumonia; s/s cough/fever, resolved with antibiotics6/25/05 – Physicians in Shanghai informed of culture results6/26 - 7/25/05 – treated with EMB/PZA/Rifapentine (?)6/28/05 – CDC determines no TST required for air passengers and co-workers

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Clinical Course (2)

7/19/05 – USPHS Quarantine Station Director recommended to Shanghai Hosp. MD to: – Start treatment with:

SM 1g IM QDPAS 4 gms BID/Levofloxacin 1 gm QD

– Assure 3 negative AFB smears– Ensure patient completes at least 4 days Rx

before return to US/max of 14 daysPATIENT RETURNS TO US 7/25/05!!

Clinical Course (3)

Patient placed DOT (5 days/wk)Patient evaluated monthly by PA DOH TB provider with monthly labsPatient co-managed with TB experts at Northeastern Regional Training & Medical Consultation Consortium (RTMCC); frequent phone consultation and visits 8/4/05, 3/16/06, and 11/17/06

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Questions & Points for Clarification

Initial Management Links

PA DOH TB Control PA DOH Bureau of Community Health Systems (BCHS) Public Health Physician CDC (Div. TB Elimination)/USPHS Quarantine EmployerChinese Embassy RTMCC (Northeastern Regional Training & Medical Consultation Consortium) Clinic physicianDOH Office of Legal Counsel (HIPAA) Patient’s wifeRegional Tuberculosis Consultant

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Radiographic Findings

CXR: 4/05 CXR with RUL infiltrate/volume loss

6/21/05 CXR in China showed RUL infiltrate

8/4/05 CXR in NJ showed RUL fibrosis with volume loss and elevation of the right hilum

CXR 8-4-05 (NJ)

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Treatment

9/15/05 – National Jewish Medical Research Center (NJMRC) reports preliminary sensitivities:– PT resistant to all first-line drugs; sensitive

to EMB and Ethionamide at very high doses;

– Tentative sensitivity to: RBT/Moxifloxacin/Linezolid/Levofloxacin

Did not receive final confirmed sensitivities until 11/5/05

Drug Susceptibility Testing Results - NJMRC

TENT. S<=0.5MOXIFLOXACIN

TENT. S<=4.0LINEZOLID

TENT. S<=2.0LEVOFLOXACIN

TENT. S0.12RIFABUTIN

S08.0 MCGPAS

S060.0 MCGCYCLOSERINE

1006.0 MCGAMIKACIN

1006.0 MCGKANAMYCIN

10010.0 MCGCAPREOMYCIN

1004.0 MCGSTREPTOMYCIN

1002.0 MCGSTREPTOMYCIN

S010.0 MCGETHIONAMIDE

S07.5 MCGETHAMBUTOL

1001.0 MCGRIFAMPIN

1001.0 MCGISONIAZID

1000.1 MCGISONIAZID

SENSITIVE (S)% RESISTANT CONC. DRUG

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Treatment Regimen

6/28/05 to 7/25/05 : Rifapentine, EMB, PZA

7/15/05 to 7/25/05: Levofloxacin

7/26/05 to 8/4/05: Streptomycin (1 gm IM qd), Levofloxacin (1 gm p.o. qd), PAS (4 gms p.o. BID)

8/5/05 to 11/8/05: Rifamate (2 caps p.o. qd), Vit B6 (50 mg p.o. qd)

Rifabutin 300 mg p.o. qd 11/8/05 to present Levaquin 500 mg p.o. qd 11/8/05 to present PAS 4 gm p.o. BID 11/8/05 to 7/19/06PAS 4 gm p.o. qd 7/21/06 to 7/30/06PAS discontinued 7/31/06Cycloserine 1000 mg p.o. qd 11/8/05 to 11/21/05 Cycloserine 750 mg p.o. qd 11/21/05 to 12/2/05 Cycloserine 500 mg p.o. qd 12/2/05 to 12/16/05 Cycloserine 250 mg p.o. qd 12/16/05 to present

x7 days/wkDOT x5 days/wk for 24 mos.

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Questions & Points for Clarification

Bacteriology

NegativeNegative“3/16/06

NegativeNegative“8/4/05NegativeNegative“8/7/05NegativeNegative“8/8/05

NegativeNegative“8/1/05

NegativeNegative“11/21/06

NegativeNegative“2/14/06NegativeNegative“2/14/06NegativeNegative“2/13/06NegativeNegative“2/9/06

NegativeNegative“8/1/05M. gordonaePositiveNegative“7/26/05M.tbPositiveNegative“5/6/05M.tbPositiveNegative“5/5/05M.tbPositiveNegativeSputum4/29/05

IDENTIFICATIONCULTURESMEAR SOURCEDATE COL.

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Patient Weights

PAS discontinued7/31/06

Patient WeightDate

129 lbs11/22/06127 lbs10/25/06122 lbs 9/15/06120 lbs (wt loss 18%)8/18/06

127.5 lbs4/7/06136 lbs12/12/05141.5 lbs7/26/05146 lbs5/5/05

Cycloserine Levels

9.0 ug/ml8/15/0612.9 ug/ml6/7/0614.9 ug/ml5/9/0611.2 ug/ml4/5/0612.4 ug/ml3/8/06

Starting 12/16/06250 mg daily

18.5 ug/ml1/27/06500 mg daily14.5 ug/ml12/15/05750 mg daily34.3 ug/ml11/21/05

Dosage (Initially 1000 mg/d)

Level (Range:8-20 µg/ml)

Date

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Complications of Treatment

Weight loss (secondary to diarrhea & loss of appetite)Oral thrushTinea crurisFatigueIntermittent fevers (especially in early treatment phase)Loss of work (off work 2/9/06—8/2/06)HeadachesAbdominal painsLoss of appetite (food did not taste right)Mild pancytopenia (WBCs 2.3-4; H/H 10/30; plat > 100)Initial resistance to treatment from pt and wife (LTBI)

Questions & Comments

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Current Status

Patient has now completed 13 months of proposed 24 months of therapy

Recent reevaluation at RTMCC (Northeastern Regional Training & Medical Consultation Consortium)

Patient committed to completion of therapy

Radiographic Findings

CT: 2/8/06 CT of chest—RUL calcified granulomaand bronchiectasis; patchy nodular opacities LUL11/21/06 Repeat CT of chest—NJFindings: Probable active disease identified in superior segment of RLL – 10mm nodule noted without calcification. Fibronodular changes at right apex with several small calcified nodules, compatible with inactive disease

PET Scan: 11/21/06 PET Scan – NJImpression: Calcified pulmonary nodules seen at right upper lung apex are non-FDG-avid. Approx. 1.2 cm nodule seen in RLL is mildly FDG-avid, intensity of FDG uptake is less than what is commonly seen with active tuberculosis. Low grade process cannot be excluded

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CT

PET CT - Whole Body

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Bilateral Whole Body

Left Hilar Node & Right Lower Lung Nodule

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Smaller Right Lower Lung Nodule

Mediastinal Nodes

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Porta Hepatic Nodes

Bilateral Axillary Nodes

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Right Upper Lung Calcified Nodules

Summary of Radiographic Findings, Questions &

Comments

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Questions Remaining

If wife agrees to LTBI treatment, what medication should be used and for how long?Should patient be offered surgical removal of RUL?If surgical removal of RUL, how long should therapy continue?

Lessons Learned

Use TB experts early and oftenCultural competent care very important when dealing with foreign bornUse of patient advocate of same cultural background extremely helpfulPlan to spend significant staff and provider time on patient educationWork closely with patient’s employer recommendations

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Final Comments

Thank you!!!