Anti tuberculosis treatment regimens
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Transcript of Anti tuberculosis treatment regimens
STANDARD REGIMENS OF ATT DRUGS
• The three major actions of anti-tuberculosis drugs are 1) Bactericidal action,defined by the ability to kill actively growing bacilli rapidly 2) Sterilizing action,defined by the ability to kill the semi dormant organisms 3) Prevention of emergence of drug resistance
Isoniazid is the most potent bactericidal drug,followed by rifampicinRifampicin and pyrazinamide are important for sterilizing the TB lesions and preventing disease relapse
• Among the first line anti-tubercular drugs,isoniazid and rifampiicin are most effective in preventing the emergence of drug resistance • Streptomycin,ethambutol and para-amino salicylic acid are less so• And thioacetazone and para-amino salicylic acid are the least effective
for the purpose
• Standardized treatment means that all patients in a defined group receive the same treatment regimen. Standard regimens have the following advantages over individu- alized prescription of drugs:• Errors in prescription – and thus the risk of development of drug
resistance – are reduced;• Estimating drug needs, purchasing, distribution and monitoring are
facilitated• Staff training is facilitated and costs are reduced• Maintaining a regular drug supply when patients move from one area to
another is made easier;• Outcome evaluation is convenient and results are comparable.
WHY ARE STANDARD REGIMENS REQUIRED?
• All regimens have two phases:
• Initial intensive phase: Designed to kill actively growing and semi dormant bacilli,,resulting in shorter duration of infectiousness usually with rapid smear conversions after 2-3 months of treatment
•Continuation phase: Designed to eliminate most residual bacilli and decreased failures and relapses
GROUP 1 GROUP 2 GROUP 3 GROUP 4 GROUP 5
Rifampicin
Isoniazid
Pyrazinamide
Ethambutol
Streptomycin
Kanamycin
Amikacin
Capreomycin
Viomycin
Ciprofloxacin
Ofloxacin
Levofloxacin
Moxifloxacin
Gatifloxacin
Ethionamide
Prothionamide
Cycloserine
Terizidone
PAS
Thioacetazone
Clofazimine
Amoxicillin/Clavulinate
Linezolid
Imipenem/Cilastin
Clarithromycin
High dose Isoniazid
CLASSIFICATION OF ATT DRUGS
Aims of Chemotherapy of TB are to:• Cure the patients of TB by the shortest duration of drug
administration with minimum interference with their living• To Prevent death from TB or late sequelae of disease• To prevent relapse of TB• To prevent emergence of drug resistance• To reduce transmission of disease to people both within and outside
the community
Treatment of smear positive PTB• Most regimens are given for a total duration of six months,this being currently the
shortest required• Regimens that do not contain pyrzinamide initial intensive phase must be given for
longer than six months• The current standard regimen prescribed by WHO and IUATLD(international Union
against tuberculosis and lung diseases) comprises of four drug regimen in initial intensive phase and two drug in continuation phase(2HRZE/4HR or 2SHRZ/4HR)• However for individual cases with extensive disease and slow bacteriological
conversion prolongation of pyrzinamide beyond two months is acceptable and prolongation of treatment to 9months may aLos be considered• Intermittent regimens with four months of daily doses with four drugs followed by
two drugs in continuation phase is shown to be highly effective in recent studies(2SHRZ/4H*3 R*3
Treatment of smear negative pulmonary TB• In many countries around 50 percent of patients have been found to be
having active pulmonary TB without immediate bacteriological confirmation• The WHO recommends in the latest guidelines the use of six month
treatment regimens consisting of daily isoniazid,rifampiicin,ethambutol and pyrazinamide followed by daily or thrice-weekly isoniazid and rifampiicin for another four months in the treatment of new cases of smear negative PTB• ETHAMBUTOL may be omitted for some patients with non-cavitatory
smear negative PTB who are known to be HIV-negative and children with primary TB
Treatment categories and sputum examination schedule under RNTCP
• Treatment categories under RNTCP are CAT-1, 2 &3• CAT-1 includes: New sputum smear positive, Seriously ill sputum smear negative,Seriously ill extra-pulmonary TBUnder CAT-1,2(HRZE)3 and 4(HR) is the standard regimen.If sputum remains postive at the end of I.P, intensive treatment is continued for 1 more month and continuation phase is started.Sputum is tested at the end of 3rd month and then 5th month and at end of treatmentIf sputum is negative,continuation phase is started and sputum tested at end of treatment.In any case,if sputum remains postive at the end of 5th month patient is considered as failure and CAT-2 is started
• CAT-2 includes: Sputum smear postive relapse Sputum smear postive failure Sputum smear postive treatment after failure Others which include sputum smear negative and extra pulmonary TB relapse and failure.• The standard regimen is 2(HRZES)3 1(HRZE)3 and 5(HRE)• If sputum postive after I.P,continue I.p for 1 mother month and start
C.P. Sputum is tested at end of 4th , 6th and 9th month• If sputum negative after I.p, continuation phase is started and
sputum is tested at 5th month and 8th month
• CAT-3 Includes new sputum smear negative and extra pulmonary TB who are not seriously ill• The standard regimen is 2(HRZ)3 and 4(HR)3.• Sputum is tested at end of I.p and if postive re-register the patient as failure and start CAT-2 If negative,continuation phase is started and sputum tested at end of treatment
Management of patients who interrupt treatment• Patient compliance is found to be very less in many parts of world
especially in developing and under-developed countries.• And so,it is important to know about management of such patients
and the treatment protocols based on length of interruption,period of treatment used and status of sputum smear.
•Management of patients who were smear negative at diagnosis and who interrupt treatment• If treatment received before interruption is less than 1 month and Length of interruption is: Less than 2 months,no sputum smear test is required,,treatment is resumed More than 2 months,sputum test is done and if negative,treatment is resumed but if postive,,patient is registered as new sputum smear postive and CAT-1 is started afresh• If treatment received is more than 1 month and length of interruption is:Less than 2 months ,no sputum smear is required and treatment is resumedMore than 2 months,sputum is tested,,if negative treatment is resumed but if postive,,Patient is registered as treatment after default and CAT-2 is started
•Management of sputum postive cases who interrupt treatmentIf treatment received is less than 1 month and length of interruption is• Less than 2 weeks,no sputum smear test is required and Treatment can be
resumed with CAT-1• 2-7 weeks,no sputum test is required but treatment is started afresh with CAT-1• More than 8 weeks,sputum test is done and if:Postive,re-registered as new case and CAT-1 started afreshNegative,resume cat-1 treatment
If treatment received before interruption is 1-2 months and length of interruption is less than 2 weeks then no Sputum smear examination is required and CAT-1 treatment can be resumed
• If treatment received is more than 2 months and length of interruption is:
Less than 2 weeks,sputum smear is not done,treatment is resumed
2-7weeks, sputum smear is done and if postive,I.P is given for 1 extra month ,,if negative,CAT-1 is resumed,,
More than 8 weeks,,sputum smear is done and if postive,,CAT-2 is started,,If negative,,CAT-1 is resumed
• Management of sputum postive retreatment cases who interrupt treatment• If treatment received before interruption is less than 1 month and length
of interruption is:Less than 2 weeks,no sputum test is required and treatment continued
with CAT-22-7weeks,no sputum test is required but CAT-2 started afreshMore than 8 weeks,sputum test up is done,,if postive—CAT-2 is started
afresh,,,if negative– CAT 2 is resumed
• If treatment received before interruption is 1-2 months and period of interruption is:
Less than 2 weeks,,sputum test is not required and CAT 2 continued2-7weeks,,sputum test is done,,and if postive,,I.P is given for 1 extra
month but if negative CAT 2 resumedMore than 8 weeks,sputum test is done,,if postive,,CAT-2 started
afresh,,if negative,,CAT-2 resumed
• If treatment received before interruption is more than 2 months and period of interruption is:
Less than 2 weeks,no sputum test is required and CAT-2 is resumed2-7 weeks,sputum test is done,if postive,,CAT-2 started afresh,,if
negative CAT-2 resumedMore than 8 weeks,,sputum test is done and if postive,,CAT-2 is started
afresh and if negative CAT-2 is resumed
TREATMENT OF MONO-DRUG resistant PTB
• For those with streptomycin resistance,it is obviously reasonable to stick to conventional short course regimens
• For patients with isoniazid resistant TB ,following two approaches have been recommended: 1) Continuation of R,E&Z for a further 10months or R+E for 12 months after having administered HRZE for initial 2 months2)No modification of initially administered four drug regimen with it being given throughout the 6month period is another approach.If patients are already known to have isoniazid resistance at commencement of therapy,a nine month regimen comprising of 2SRZE and 7ER is recommended • For patients with rifampiicin resistance, a rare occurrence except in HIV PATIENTS regimen comprising
of HZE for 18-24 months has been recommended although some studies showed that duration of treatment can be reduced to 9-12 months with addition of fluoroquinolone to this three drug regimen
Treatment of MDR-TB• A patient with MDR-TB should receive a regimen comprimising at
least four to five of these SLD for initial months followed by three to four drugs subsequently• One regimen recommended by WHO consists of treatment with
ETHAMBUTOL,ETHIONAMIDE,PROTHIONAMIDE,OFLOXCIN OR CIPROFLOXCIN,PYRAZINAMIDE AND AMINOGLYCOSIDE,CAPREOMYCIN for first 6 months followed by first four drugs being administered for a further 12 to 18 months• The optimum duration of patients with MDR-TB is unclear although
WHO along with other authorities has recommended a minimum of 18month regimen
RNTCP AND MDR-TB• RNTCP is using a Standardised Treatment Regimen (Cat IV) for the treatment
of MDR-TB cases (and those with rifampicin resistance) under the programme. Cat IV regimen comprises of 6 drugs- kanamycin, ofloxacin (levofloxacin)†, ethionamide, pyrazinamide, ethambutol and cycloserine during 6-9 months of the Intensive Phase and 4 drugs- ofloxacin (levofloxacin), ethionamide, ethambutol and cycloserine during the 18 months of the Continuation Phase. • p-aminosalicylic acid (PAS) is included in the regimen as a substitute drug if
any bactericidal drug (K, Ofl, Z and Eto) or 2 bacteriostatic (E and Cs) drugs are not tolerated.
Treatment of MDR patients who interrupt treatment: • Cat IV patients in IP/CP who miss doses:All the missed doses during IP must be completed prior to switching the patient to CP. Similarly all
missed doses during CP must be administered prior to ending treatment.• Cat IV patients who interrupt treatment for less than 2 months during IP:When the patient returns to resume treatment the IP will be continued, however the duration of
treatment will be extended to complete IP• Cat IV patients who interrupt treatment for less than 2 months during CP:When the patient returns to resume treatment, the CP will be continued, however the duration of
treatment will be extended to complete the CP. The follow up cultures will be done as per the revised schedule.
• Cat IV patients who default (interrupt treatment for 2 or more months) and return back for treatment:
Such patients will be given an outcome of “default” and then will be re-registered for further treatment which is based on the duration of default.
• If period of default is less than 6 months and treatment duration prior to default is:
Less than 3 months,,re-register and start CAT-4 afreshIf 3months- End of IP,,AFB Culture is done and if postive then re-start
CAT-4 and sensitivity for 1st line and 2nd line TB drugs is done,,if negative continue I.P, Repeat culture and start C.P
If more than 3 months and during C.P, AFB culture is done,,if negative C.P is continued,,if postive DST FOR 1st and 2nd line is done and individual regimen is formulated
• If period of default is more than 6 months then culture is done.• If culture is postive,then DST for FLD &SLD is done,,if MDR,then CAT-4
is started afresh after re-registering the patient,,if XDR,then CAT-5 is started • If culture is negative,no treatment is required but patient is followed
up periodically