MULTI DRUG RESISTANT TUBERCULOSIS (MDR)

Types Of Resistance
Primary drug resistance: Presence of resistance to anti TB drugs in a patient who has not received anti TB drugs in the past Acquired drug resistance: Resistance to anti TB drugs in a patient during the course or after treatment with ATT

 Natural drug resistance: Strains of tubercular bacilli naturally resistant to anti TB drugs. eg: M. Bovis is resistant to PZA Multi drug resistance: Development of resistance to both INH and Rifampicin with or without resistance to other anti TB drugs

Factors contributing to drug resistance

Biological factors: Genetic predisposition, large bacillary population, type of lesions, HIV Clinical factors: Total number of drugs used, duration of treatment, dosage, drug quality, absence of continuous drug supply Social factors: Poverty, lack of awareness, drug default, addictions

Diagnosis of MDR
Detailed treatment history including history of contact Progressive radiological worsening Absence of clinical improvement in spite of optimal ATT Persistence of sputum positivity Fall and rise phenomenon

Confirmative diagnosis of MDR Tuberculosis

By sputum culture and sensitivity testing to anti TB drugs

1. Conventional culture
2. Rapid culture- BACTEC

Drugs used in MDR

Aminoglycosides: Kanamycin, Capreomycin Quinolones: Ciprofloxacin, Ofloxacin, Laevofloxacin Thioamides: Ethionamide, Prothionamide Phenazines: Clofazamine Macrolides: Azithromycin, Clarithromycin Rifampicin derivatives: Rifabutin, Rifapentene Immunomodulators: Levamisole, TNF, Gamma interferon Others: PAS, Cycloserine

Other treatment modalities

Salvage surgeries like Lobectomy, Pneumonectomy, Decortication, Plombage, Thoracoplasty can be considered in surgical cases

Principles of MDR treatment

First line drugs preferred Previously unused drugs tried INH included in all regimens Bactericidal drugs preferred Minimum of 4 drugs & preferably 6-7 drugs used Never add a single drug to a failing regimen Avoid intermittent regimens

Principles of MDR treatment

Drugs started according to the sensitivity pattern Cross resistant drugs avoided Include a parentral aminoglycoside, quinolone in all regimens Drugs used for a minimum of 12-18 months after sputum negativity Most toxic drugs can be gradually withdrawn after sputum conversion Treatment must be supervised

Complications of TB
Haemoptysis:

Causes are Rupture of Rasmussen aneurysm Erosion of blood vessel by broncholith Aspergilloma in a cavity Post tubercular bronchiectasis Rupture of fibrotic bands Anastamosis between bronchial and pulmonary artery

Complications of TB
Pleural complications: PLEF, empyemas, pneumothorax, bronchopleural fistula Bronchiectasis TB laryngitis Open negative syndrome Secondary bronchitis Cor pulmonale Respiratory failure Amyloidosis Disseminated Koch's Scar carcinoma

TB & HIV
HIV increases susceptibility to infection with tuberculosis by 10 folds Progression of TB more rapid in HIV and vice versa Higher incidence of extra pulmonary TB in HIV patients Higher risk of intolerance to ATT, relapse and MDR Poses diagnostic difficulties due to atypical features and smear negativity

PTB features Clinical picture

Chest Xray Sputum smear

Early HIV Resembles post primary TB

Well localized, often cavitatory disease Often positive

Late HIV Resembles primary TB

Infiltrates common with dissemination Often negative

BCG VACCINE
Live attenuated vaccine Does not protect against infection, but efficacy in preventing disease varies from 20-80% Route intradermally Adverse effect: keloids, ulcers, lymphadenitis, disseminated infection

Mantoux (tuberculin) skin testing

Standard method of identifying those with

tuberculosis infection
Intradermal administration of 5 units of PPD Induration > 10 mm considered positive test Induration > 5mm positive in those with HIV, close contact with sputum positive cases, those with XRC changes Test is neither sensitive nor specific False negative occurs in HIV positive, on steroids etc

Chemo Prophylaxis
1. 2. 3. Used to prevent the development of the disease Drug used is INH at dose of 5-10 mg / kg / day for 6 months Indicated in Mantoux > 10mm with risk factors like DM, steroid therapy, malignancies Mantoux > 5mm with HIV positive, contact with infectious person, lesion on chest X-ray Mantoux > 15mm with age < 35 yrs with no risk factors