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