Dr. Manu Mohan K

Associate Professor

Pulmonary Medicine

DRUG RESISTANT TUBERCULOSIS

DEFINITIONS

• Drug resistance is defined as a decrease in sensitivity to a drug of a sufficient degree.

• A strain is considered resistant when 1% or more of the bacterial population was resistant to a designated concentration of drug.

MULTI – DRUG RESISTANT TUBERCULOSIS

• Mycobacterium tuberculosis resistant to at least Isoniazid and Rifampicin.

TERMINOLOGY

• Wild strain

• Natural or Primary resistance

• Acquired resistance

MECHANISMS

• Mutations

• Interference in uptake, penetration

• Insusceptible metabolic pathways

• Destruction of drugs

• Fall and rise phenomenon

FACTORS

• Clinical

• Administrative

• Patient co-operation

DRUG SUSCEPTIBILITY TESTS

• Conventional methods

• Rapid methods

• Radiometric method-BACTEC

• Luciferase reporter assay

• Mycobacterium Growth Indicator Tube

• Gene based tests

• DNA finger printing

SECOND - LINE ANTITUBERCULOSIS DRUGS

• Aminoglycosides

• Thioamides

• Fluoroquinolones

• Cycloserine

• Para Amino Salicylic acid

• Others

BASIC PRINCIPLES FOR MANAGEMENT OF MDRTB

• Specialised unit

• Designing appropriate regimen

• Which regimens?

• Whether took as prescribed and how long?

• What happened bacteriologically?

• Reliable susceptibility testing

• Reliable drug supplies

• Priority for prevention

• MDRTB is a consequence of poor treatment

HOW TO ASSESS INDIVIDUAL CASES?

• Think of following

• Lab report – error?

• Retreatment regimen – correct?

• Patient aware of giving true history?

• Question the family members

• Considering criteria of failure of retreatment regimen

• Persistent sputum positive

• Lab report should not be considered uncritically

• Radiological deterioration

• Clinical deterioration

CHOOSING CHEMOTHERAPY REGIMEN – BASIC PRINCIPLES• It is assumed that apparent drug

resistant tuberculosis bacilli will be resistant to Isoniazid

• Second line drugs – less effective more toxic

• Patient and staff should have clear idea that the regimen stands between patient and death

• Patient must try to tolerate

• Last battle – do not aim to keep drugs in reserve

• Prescribe drugs which patient has not had previously

• Initial regimen should consist of at least 3 drugs preferably 4 or 5 to which bacilli are likely to be fully sensitive

• It is desirable to use in combination an injectable aminoglycoside

• When patients sputum has converted to negative, you can withdraw one or more drugs, preferably weaker one causing side effects

• Continuation phase should be at least 18 months after sputum conversion.

• Treatment should be daily and directly observed

• Mandatory to monitor bacteriological results (smear and culture) monthly from 2nd month until 6th month, and then quarterly till the end of treatment.

ACCEPTABLE REGIMENS

• If susceptibility test not available start at least 3 never used drugs (Kanamycin, ethionamide, fluoroquinolone and pyrazinamide) followed by 2 drugs best tolerated and more effective( fluoroquinolone and ethionamide)

• If susceptibility test result available and resistant to isoniazid,

• Rifampicin, aminoglycosides, pyrazinamide, ethambutol for 2-3 months and then continued with ER for total of 9 months

• Resistant to Isoniazid and Rifampicin (with or with out streptomycin)

• 5 drug regimen mandatory. Ethionamide, fluoroquinolone, aminoglycoside, Pyrazinamide and Ethambutol followed by Ethionamide, fluoroquinolone and Ethambutol

• Resistance to Isoniazid, Rifampicin and Ethambutol

• Aminoglycoside, Ethionamide, Pyrazinamide, fluoroquinolone and Cycloserine followed by Ethionamide, fluoroquinolone and Cycloserine.

SURGERY

DOTS PLUS

HIV

XDR-TB