TREATMENT OF TUBERCULOSIS COMPRISES OF 2 PHASES AS BELOW
An initial phase
A continuation phase
In initial phase, four medications are used for up to 2 months i.e., Isoniazid, rifampicin, pyrazinamide and ethambutol. The purpose of concurrent use of 4 drugs during the initial phase is to reduce bacterial population as soon as possible and to prevent drug resistant bacteria. Administration of above-mentioned medicines in combination is recommended during initial phase unless and until any one of drug cannot be given because of resistance or intolerance.
If resistance to Isoniazid has been established before starting treatment, then STREPTOMYCIN can be used.
In continuation phase, 2 drugs Isoniazid and rifampicin are given for further 4 months. Longer treatment is required for meningitis and if spinal cord involvement.
This regimen is UNSUPERVISED TREATMENT, there is no need of monitoring. However, for resistant organism modification of regime required. Above mentioned regime, is First line anti-TB drug of tuberculosis.
PREGNANCY AND BREAST FEEDING
The first line anti -TB drug of tuberculosis may be used during pregnancy and breast feeding. STREPTOMYCIN shouldn’t be used in pregnancy.
CHILDREN
Children are given Isoniazid, rifampicin, pyrazinamide and ethambutol for the first 2 months followed by Isoniazid and rifampicin during the next 4months. In children, streptomycin should be avoided due to irreversible auditory nerve damage. however, it can be used in children for initial 2 months in tuberculosis meningitis. In past, ethambutol because of optic neuritis was avoided in children because it is difficult to monitor its visual toxicity in children. New literature review that in children ethambutol can be given as (15-25mg/kg) or 20mg /kg than 15mg / kg in adults. The higher dose of ethambutol in children is due to pharmacokinetics differences as peak serum concentration of ethambutol is lower with adult dose i.e., 15 mg/ kg. Treatment of tuberculosis requires specialized knowledge particularly if resistant organism or non-pulmonary organ is involved.
WHAT IS DOT……?
DOT means DIRECTLY OBSERVED THERAPY in which professional watch out administration of each and every dose of drug to prevent the non-adherence of patient to treatment, to check out response of patient against TB and to monitor any serious adverse profile of regimen.
SUPERVISED TREATMENT
These patients are given Isoniazid, rifampicin, pyrazinamide and ethambutol (or streptomycin) 3 times week under supervision for the first 2 months followed by Isoniazid and rifampicin 3 times a week for a further 4 months. To facilitate such supervision through DOT, intermittent schedule for drug administration becomes very important. Al though WHO also endorse DOT but in under developing country despite of giving intermittent doses, daily administration of doses are recommended
IMMUNE COMPROMISED PATIENT
Confirmed M. tuberculosis infection sensitive to first _line drugs should be treated with a standard 6 months regimen.
After completing treatment patients should be closely monitored.
Care must be taken in immune compromised patient for potential Hazardous interaction especially with antiretroviral and antituberculosis Starting with initial 2-month phase because it’s increase risk of immune reconstitution syndrome. (Collection of inflammatory disorders).
Patients who receiving immunosuppressant cytotoxic or on long term treatment with systemic corticosteroids and having evidence of LATENT TUBERCULOSIS then chemo prophylaxis is required which may be either use of Isoniazid alone for 6 months or Isoniazid and rifampicin for 3 months.
WHAT SHOULD BE MONITOR DURING TB TREATMENT?
Since Isoniazid, rifampicin and pyrazinamide are associated to liver toxicity, liver function should be checked before starting treatment especially,
If patient have alcohol dependence or having pre-existing liver disease.
If patient develop fever, malaise, vomiting, jaundice or severe liver damage then attention should be paid to symptoms of liver disease. However, if serious illness of liver occurs then all above mentioned medicines should be stop immediately and fluoroquinolone, cycloserine and ethambutol should be considered.
RENAL
Renal function should be checked before starting treatment especially with streptomycin and ethambutol. if renal impairment exits then dose should be adjusted and closely monitor for any adverse effect.
OPTIC
With ethambutol visual toxicity is associated so it’s should be monitored during treatment.
ISONIAZID
Isoniazid is the cheapest and very effective anti-TB drug which always be included in anti-tuberculosis regimen unless and until there is specific contra indication of it.
Why pyridoxine is given with isoniazid?
Peripheral neuropathy is common side effect of isoniazid which is more likely to occur with pre-existing risk such as diabetic, alcohol dependence, chronic renal failure, malaise, mal- nutrition and HIV infections. 10-20mg pyridoxine daily should be given prophylactically from the start of treatment.
RIFAMPICIN
Like Isoniazid, RIFAMPICIN is also included in anti-tuberculosis regimen unless and until there is any specific contra indication.
Rifampicin during first 2 months of treatment disturb liver function and elevate serum concentration of transaminases which is common one and doesn’t require interruption of treatment.
With pre-existing liver diseases serious liver toxicity require change of treatment.
Intermittent treatment with rifampicin, shows following symptoms influenza -like, abdominal and respiratory symptoms, shock, renal failure and thrombocytopenic purpura. (approximately occurs in 20-30% OF patient)
Rifampicin induces many hepatic enzymes which accelerate metabolism of several drugs such as estrogens, corticosteroid, phenytoin, sulfonylureas and anticoagulant.
Rifampicin reduces the effectiveness of hormonal contraceptive.
RIFABUTIN
Used as prophylaxis against MYCOBACTERIUM AVIUM COMPLEX infection in immunosuppressed patient with low CD4 count
For the treatment of non-tuberculosis mycobacterium infections in combination with other medicines
For the treatment of pulmonary TB in combination with another drug.
PYRAZINAMIDE
It exerts its main effect only in the first 2 or 3 months.
It’s active against only intracellular dividing forms of Mycobacterium tuberculosis. It’s not active against M. bovis.
Liver toxicity is major side effect.
ETHAMBUTOL
It’s mainly used in the treatment if Isoniazid resistance is suspected. It can be omitted if risk of resistance is low.
Visual toxicity is main adverse effect and especially should be used with caution in children until they are 5 years old and can report about visual changes accurately.
With renal impairment toxic effect are also observed.
STREPTOMYCIN
It’s used against resistant organism. It’s used intramuscularly.
MDR-TB (MULTI DRUG RESISTANT TUBERCULOSIS)
In MDR-TB, there is resistant of at least 2 drugs i. e, Isoniazid and rifampicin. Drug resistant tuberculosis should be treated by specialist physician with experience in such cases and where appropriate facilities for infection control exits.
SECOND LINE ANTI-TB DRUG
Second line anti -TB drug are as follows
Flour quinolone (ofloxacin, ciprofloxacin, moxifloxacin, levofloxacin
Weak anti-TB drugs (prothionamide, ethionamide, p-amino salicylic acid, cycloserine and terizidone)
Injectable ANTI-TB DRUG (amino glycosides i.e., amikacin, kanamycin, capreomycin)
WHAT IS XDR (extensively resistant tuberculosis)?
XDR is extensively resistant to in which there is resistant against Isoniazid, rifampicin, one of fluoroquinolone or one of injectable of second line anti-TB drug. It’s very rare one.
NEWER ANTI-TB DRUG
BEDAQUILINE is one of the newer anti-TB drugs it’s di aryl quinolone anti mycobacterial drug. its act by blocking the ability of Mycobacterium tuberculosis to make ATP i.e., blocking the channel through which Mycobacterium receives energy. WHO approved it only for MDR tuberculosis or XDR tuberculosis where no other anti-TB drug can work. Q-T prolongation is its major side effect.
In short, every state and country have its own guidelines to counter the tuberculosis. No fix regimen will work for MDR-TB. Professional skills are required especially in designing regimen for MDR-TB by looking into following factors which are organism sensitivity to anti-TB drug, adverse effects profiles and to avoid non-adherence of patient to treatment. In future, may be an effective vaccine availability helps us in stopping the spread of tuberculosis.