Managing Complex TB Cases Diana M. Nilsen, MD, RN

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1 Managing Complex TB Cases Diana M. Nilsen, MD, RN Director of Medical Affairs NYC Department of Health & Mental Hygiene Bureau of TB Control

2 Case #1 You are managing a patient who was seen at a private doctor s office with INH resistant tuberculosis Patient has a RUL cavity and is culture positive into the 2 nd month of therapy What are the different options for treatment, and the length of therapy? Who should be informed? How should the patient s 4 and 10 year old children be treated for LTBI?

3 INH Resistant TB Initial Phase Continuation Phase Total length RIF/PZA/EMB If extensive disease consider adding a 4 th agent (FQ or IA) 2 months RIF/PZA/EMB 2 months RIF/PZA/EMB RIF/EMB 6-9 months Extend to 9 months if culture positive at 2 months Preferred regimen, even in pregnancy 9 months RIF/EMB + FQ or IA 2 months RIF/EMB + FQ or IA 12 months

4 Case #2 Patient is still infectious after 1 ½ months of INH/RIF/PZA/EMB The lab report reveals resistance to INH/RIF/PZA and sensitivity to EMB How should this patient be treated initially and for how long? When can the patient return to work/school? What else should be discussed in the management of this patient? Should the patient go for surgery? How long should the patient be followed once treatment is complete?

5 Step 1 Begin with any 1 st -line agents to which the isolate is susceptible Use any available First-line drugs PLUS One of these Fluoroquinolones PLUS One of these Injectable agents Add a fluoroquinolone and an injectable drug based on susceptibilities Pyrazinamide Ethambutol Levofloxacin Moxifloxacin Amikacin Capreomycin Streptomycin Kanamycin Step 2 Add 2 nd -line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously) Pick one or more of these Oral second-line drugs Cycloserine Ethionamide PAS Adapted from Drug-Resistant Tuberculosis: A Survival Guide for Clinicians, available from Francis J. Curry National Tuberculosis Center Step 3 If there are not 4-6 drugs available consider 3 rd -line in consult with MDRTB experts Consider use of these Third-line drugs Imipenem Linezolid Macrolides Amoxicillin/Clavulanate Clofazimine High-dose isoniazid

6 Indications for Surgery (1) Adequate 1 st and 2 nd -line anti-tb medications have failed to cure or cause M. tb cultures to convert to negative within 4 to 6 months Sufficient medications are available to treat the patient post-operatively Disease is sufficiently localized to allow lobectomy or pneumonectomy Remaining lung tissue is relatively free of disease Acceptable surgical risk, with sufficient pulmonary reserve to tolerate the resection

7 Indications for Surgery (2) Additional possible indications for surgery: Major bronchial obstruction Severe hemoptysis Bronchopleural fistula (BPF)

8 Surgery for MDR TB Patients Even after lung resection, the patient must complete a full course of treatment (i.e., months after culture conversion) with medications to which the M.tb strain is susceptible If patient is culture negative after surgery, then surgery is considered the conversion episode

9 Infection Control Issues Related to Multidrug Resistant TB Patients MDR TB patients should remain hospitalized or on home isolation if an outpatient until: 3 sputum smears are AFB-negative Clinically improved and near resolution of cough Tolerating an appropriate treatment regimen Patient agrees to DOT and it has been arranged Proper arrangements have been made for followup A home assessment should be done with evaluation for insertion of a HEPA filter in the residence

10 Situations Where Culture Conversion Should Be Confirmed Prior to Return to Work Work sites where individuals with drug susceptible TB and MDR TB should be excluded until culture conversion is confirmed: Settings where persons with HIV or other immunocompromised patients are cared for Neonatal intensive care units Patient care areas Nursing homes Congregate settings such as daycare and schools

11 Returning MDR TB Patients to Work or School Culture Conversion MDR TB patients should not return to work or school, or transferred to another congregate setting (e.g., shelter or nursing home) until culture conversion is confirmed 2 consecutive negative cultures at least 2 weeks apart Culture conversion is necessary unless the patient will be transferred to a airborne infection isolation room in the congregate setting Exceptions can be made for certain types of work settings, if all the conditions in previous slide are met Decided in consultation w/ Office of Medical Affairs

12 Follow-up of MDR TB Patients after Treatment Completion Patients with TB resistant to INH and RIF or treated without RIF/RBT Medical evaluation every 4 months during the 1 st year after treatment completion Then every 6 months during the 2 nd year Months: 4, 8, 12, 18, 24 post treatment Educate about relapse and to return if they develop symptoms

13 Case #3: Presentation 29 y/o male with DM (Type I), presented to local city hospital on 3/18/11 c/o fever x 1mo Armenian, immigrated in 2/2011 Lives with wife and 2 children (2 & 6 years old) Worked as a prosecutor in Armenia, came to US with normal CXR Ex-smoker (10PY), social alcohol, no drugs HIV negative Transferred to another city hospital 6/8/11 due to MDR-TB

14 Chest X-ray

15 Chest CT

16 Chest CT

17 Bacteriology Date Sample Smear Culture Sensitivity/MISC 3/20/11 Sputum Pos M.tb R: INH, RIF, EMB, SM, RBT, OFL, ETA 3/21/11 Sputum Pos M.tb S: PZA, KAN, AMI,CAP, CYC, PAS 3/28/11 Sputum Pos M.tb R: LEV, MOX (intermed) 4/1/11 Sputum Pos M.tb S: CAP, KAN, AMI, ETA, CYC, PAS, LZD, CLO 4/8/11-4/30/11 Sputum Pos M.tb 5/2/11 Sputum Neg 5/5/11 Sputum Neg 5/6/11 Sputum Neg M.tb 5/9/11 Sputum Pos M.tb 5/16/11 Sputum Pos M.tb 6/2/11 Sputum Neg 6/9/11 Sputum Pos M.tb S: CAP, CYC, PAS (R: EMB, KAN, RIF, RBT) 6/10/11 Fast track Pos M.tb Fast track S: PZA, SM, CAP, CYC, ETA, PAS, AMI 6/11/11 Sputum Pos M.tb 6/16/11 Sputum Neg Neg 6/17/11 Sputum Pos M.tb 6/25/11 Sputum Neg Neg 6/26/11 Sputum Pos Neg

18 Bacteriology Date Sample Smear Culture Sensitivity/MISC 7/5/11 Sputum Pos Neg 7/9/11 Sputum Pos Neg 7/18/11 Sputum Neg Neg 7/23/11 Sputum Neg Neg 7/25/11 Sputum Neg Neg 8/1/11 Sputum Neg 8/2/11 Sputum Pos 8/9/11 Sputum Neg 8/11/11 Sputum Neg 8/15/11 Sputum Neg M.tb 8/16/11 Sputum Neg 8/17/11 Sputum Neg 8/19/11 Sputum Neg 8/20/11 Sputum Neg 8/22/11 Sputum Neg 8/23/11 Sputum Neg M. fortuitum 8/24/11 Sputum Neg 8/28/11 Sputum Neg 9/2/11 Sputum Neg

19 Revised Definition XDR TB (10/06) Resistance to at least INH and RIF from among the 1 st -line anti-tb drugs (MDR TB) Plus resistance to any fluoroquinolone, And to at least one of 3 injectable 2 nd -line anti- TB drugs used in TB treatment Capreomycin Kanamycin Amikacin

20 Current weight 73 kg Unit (mg) Admission weight 75 kg DATE I N H R I F P Z A E M B S M N E T A M O X O F L C Y C C A P P A S A M I A U G M E R L Z D I F N C L O 3/21/ /5/ Pt didn t respond to 1 st line therapy 4/26/ /28/ st line DST available 5/4/ /19/ Ran out 5/23/ / 125 6/8/11 Bellevue / 125 7/1/ / /21/ /125 TID ETA dose decreased due to nausea 8/26/ /125 TID Resistant to Kanamycin; Amikacin d/c Capreomycin re-started as it had become available again Pt developed seizure 2 nd line DST available 3 rd line DST available /21/11 PATIENT DISCHARGED HOME

21 Step 1 Begin with any 1 st -line agents to which the isolate is susceptible Use any available First-line drugs PLUS One of these Fluoroquinolones PLUS One of these Injectable agents Add a fluoroquinolone and an injectable drug based on susceptibilities Pyrazinamide Ethambutol Levofloxacin Moxifloxacin Amikacin Capreomycin Streptomycin Kanamycin Step 2 Add 2 nd -line drugs until you have 4-6 drugs to which isolate is susceptible (which have not been used previously) Pick one or more of these Oral second-line drugs Cycloserine Ethionamide PAS Adapted from Drug-Resistant Tuberculosis: A Survival Guide for Clinicians, available from Francis J. Curry National Tuberculosis Center Step 3 If there are not 4-6 drugs available consider 3 rd -line in consult with MDRTB experts Consider use of these Third-line drugs Imipenem Linezolid Macrolides Amoxicillin/Clavulanate Clofazimine High-dose isoniazid

22 Discharge Plan Continue PZA, ETA, PAS, CYC, LZD, meropenem, augmentin, capreomycin months after culture conversion (was 6/25, now 8/15) Medicaid to pay for meds, DOH to administer them (except Augmentin, meropenem) Patient will be responsible for taking BID Augmentin and infusing BID meropenem via PICC line Retest 8/15/11 specimen Continue isolation Family issues Patient discharged home to private room with HEPA filter

23 Treatment of Contacts Patient s 2 children live at home with wife and parents 2 yr old converted on QFT, negative CXR 6 yr. old window QFT negative Wife and parents QFT negative DOH recommended treatment for LTBI for 2 yr old but family refused BCG??, but children already received it

24 Discussion Contact investigation & public health issues Okay for patient to stay at home with family? What to do (if anything) about positive culture from 8/15? Continue current meds? Institution started meropenem and augmentin, any experience with this?

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