Drug resistant tb
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Transcript of Drug resistant tb
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.
MECHANISMS
• Mutations
• Interference in uptake, penetration
• Insusceptible metabolic pathways
• Destruction of drugs
• Fall and rise phenomenon
DRUG SUSCEPTIBILITY TESTS
• Conventional methods
• Rapid methods
• Radiometric method-BACTEC
• Luciferase reporter assay
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.