Chemotherapy / Treatment Activities
Why is it necessary to directly observe treatment?
At least one third of patients receiving self-administered treatment do not adhere to treatment. It is impossible to predict which patients will take medicines regularly. Therefore, directly observed treatment is necessary at least in the initial phase of treatment to ensure adherence and achieve sputum smear conversion. A TB patient missing one attendance can be traced immediately and counseled. No method other than directly observed treatment has been able to achieve 85% cure rate of new smear positive cases.
What is lag period and its use?
The tubercle bacilli when exposed to a drug do not multiply for varying duration, which is called lag period. This property of the bacilli is utilized as the basis of intermittent therapy.
What is the basis of drug regimens?
Drug regimens are decided in consideration of the following facts: Mode of action of individual drugs The dose of each drug depends on minimum inhibitory concentration (MIC) i.e. the minimum drug concentration that inhibits bacterial growth in-vitro, and Minimum Bactericidal Concentration (MBC) i.e. the concentration at which bacteria are killed. MBC is usually higher than MIC. Prevention of drug resistance. Demonstration of efficacy during drug trials and field trials in terms of sputum conversion and relapse. Minimal side effects. Cost effectiveness. Operational feasibility.
What is the role of each drug during intensive phase?
INH has very high early bactericidal activity (EBA) and acts on rapidly multiplying extra-cellular bacilli. It accounts for 95% kill in bacillary population. Remaining bacilli metabolize slowly and are killed preferentially by ‘Rifampicin’. INH is also most effective drug for preventing resistance to other drugs. On the other hand, other drugs are not so efficient in preventing resistance to INH, which is therefore more common. Rifampicin also has high bactericidal activity but starts acting little later. It acts on rapid as well as intermittently (found in caseous lesions) multiplying bacilli. Pyrazinamide acts on intra-cellular bacilli that are particularly inhibited by acid environment inside macrophages. Ethambutol is the companion drug to prevent drug resistance.
What is the role of INH and Rifampicin during Continuation Phase?
Rifampicin is the main sterilizing drug in this phase. The role of INH is mainly to prevent drug resistance to Rifampicin.
Why Pyrizinamide or Ethambutol is not included in Continuation phase of Cat I?
Pyrizinamide has no additional benefit if given beyond 2-3 months, as seen in clinical trials. Ethambutol is not required because the chances of drug resistant to INH or Rifampicin developing in continuous phase is negligible as the number of bacilli is drastically reduced in this phase.
Why Cat II cannot be given for serious extra-pulmonary cases like TBM?
Streptomycin has limited penetration to membranes, however it can be given intra-thecal in case of serious cases of TBM.
Why 3 drugs are given during Continuation Phase of Cat II?
The re-treatment cases are more likely to harbor drug resistant bacilli, at least to INH. Therefore, ethambutol is added to prevent drug resistance to INH or Rifampicin.
Why only 3 drugs are given during Intensive Phase of Cat III?
Smear negativity means there are few bacilli and thus negligible chances of resistant mutant bacilli being present.
Why does treatment fail?
Most common reason of treatment failure is the failure to observe drug administration, which commonly results in treatment failure.
What are the special precautions to protect Rifampicin?
Rifampicin should be protected since resistance to it results in much higher failure and relapse rates. Cross-resistance also occurs to all other Rifamycins. It should never be used without direct observation. Its use should preferably be restricted to public health Institutions and experts. The regimens, which minimize risk of resistance to Rifampacin, should only be used.
Why should we check sputum smear status at 2/3 months?
This information is essential for prolongation of intensive phase by one month, which reduces risk of failure and relapse. It is an important management tool and reflects on the quality of lab, quality of treatment observation during Intensive Phase and proportion of defaulters. The smear status at the end of Intensive Phase also predicts the probability of cure.
What to do if an error in smear microscopy is detected during cross checking, especially on follow up and at end of treatment?
If error is detected at the time of diagnosis, check for other smear results, X-ray and whether patient has been started on treatment. If the patient was missed on diagnosis, he should be traced and put on treatment. If an error is detected on follow-up smear examinations, no change in treatment is undertaken based on the results of cross examination. To some extent, there are built-in mechanisms to handle this problem for e.g., re-examination of sputum smears after 5 months of treatment among those who are smear positive at 4 months. However, full efforts must be made to keep the errors on follow-up examinations to be minimum.
What is the rationale of switching to continuation phase even if the follow-up smear examination at end of extended Intensive Phase shows presence of AFB?
With treatment of high efficacy, smears can be positive at 2-3 months due to presence of dead bacilli. Therefore, treatment failure based on smear examination is not considered until 5th month of treatment.
Switching over to self-administered treatment in continuous phase carries a risk of non-adherence as it conveys relaxation in treatment at a time when patients’ symptoms are telling that he no longer needs treatment?
The treatment during continuous phase is partially supervised and adherence is sustained by continued motivation and health education of the patient. Operationally, it may not be feasible to supervise each dose of continuation phase. However, all those patients who have a history of being irregular, alcoholics etc., should be fully supervised. Other cases that are willing to be fully supervised during continuous phase should be encouraged.
Is there a higher risk of failure among those patients who continue to be smear positive at the end of Intensive Phase?
Assuming that the history of previous treatment was taken properly at the time of diagnosis, most patients who continue treatment get cured, though relative risk of failure among such cases is higher compared to those who are smear negative at the end of intensive phase.
How valid is the policy of adding Streptomycin for re-treatment cases?
Only a proportion of patients put on re-treatment regimen are failure cases and likely to be resistant to one or more drugs. Cohort analysis of patients treated so far in our country shows that two-thirds of the patients remaining smear positive after 5 moths of treatment on Cat I and subsequently treated with Cat II have been successfully treated.
Efficacy of twice weekly (TW) regimen has been demonstrated in many trials. Would such regimen not reduce the workload on DOT workers?
In twice weekly regimen, if patient misses one dose, it amounts to once weekly medication, which is more than lag period for most drugs and increases the risk of development of resistance. Twice weekly regimen are also more toxic because of immunologically mediated adverse effects.
In what conditions can Treatment be prolonged?
Continuation Phase may be prolonged upto 7 months with INH & Rifampicin in cases of TBM, Miliary and Spinal TB
What are the precautions to be undertaken during ATT?
(i) Pyridoxin supplementation to pregnant females, diabetics,chronic alcoholics (ii) Discourage alcohol consumption during treatment (iii) Monitor for symptoms and signs consistent with hepatic damage (iv) Liver function tests every 2 - 3 months for those at high risk (v) Sterptomycin is contra - indicated during pregnancy (vi) Monitor side effects of sterptomycin specially in elderly: tinnitus, vertigo, hearing tests for higher frequencies which are affected first, Romberg’s Test (vii) Avoid loop diuretics, which potentiate side effects of ‘Streptomycin’. (viii) Analgesics for arthralgia which usually does not require withdrawal of anti-TB treatment. (ix) In case of suspected preexisting ophthomological disease, assess visual acuity and colour vision before starting treatment (x) Stop ethambutol in case of side effects, which are reversible (xi) Avoid ethambutol among children < 6 years (xii) Avoid ‘Streptomycin’ and ‘Ethambutol’ in renal disease (xiii) Avoid Antacids that decrease drug absorption (xiv) Women to use non- hormonal contraceptive methods (xv) In case of hypersensitivity reaction, withdraw treatment completely and desensitize later (xvi) Monitor steroids, oral anti-coagulants, anti-convulsants, oral hypoglycaemics, tranquilizers, theophylline, beta-blockers, calcium channel blockers, digoxin when given concurrently with Rifampicin. Evaluate each patient by interview and clinical examination for emergence of side effects at the end of each month.
What is the role of Fluroquinolones in treatment of TB?
These drugs are moderately effective with other drugs for MDRTB and should only be given if standard drugs not tolerable.
What are the problems in treatment with second line drugs?
(i) These drugs are less efficacious and more toxic.
(ii) They possess cross resistance to first line drugs
(iii) Most patients needing such treatment are difficult to hold e.g. alcoholics, drug addicts, migrants etc,
(iv) Hospitalization is a must for observation and regularizing treatment. Ambulatory treatment is possible only after tolerance and regularity assured.
(v) It is irrational for any country to divert resources to treating with second line drugs until full potential of SCC regimen has been achieved.Requirement of the reserve drugs indicates poor program.
What are the guidelines for treatment of TB among children?
If a child is diagnosed to have tuberculosis, a full course of treatment has to be given. Children rarely suffer from smear positive disease. As a result, there are few bacilli in the lesions and no chance of resistant mutants being present. The recommended regimen is Cat III. The dose of drug has to be calculated in mg per kg body weight and given from loose drug stock. For patients with military or meningeal TB, a fourth drug, streptomycin can be added and the total duration made to 9 months.
Why is it necessary to carefully elicit history of previous treatment?
The history of previous treatment should be elicited clearly for deciding on the proper category of treatment for the patient. Otherwise, cases may be given wrong treatment that may lead to treatment failure.
How to treat TB patient also suffering from liver disease?
In chronic liver disease, 2 EHRZ / 6 HR can be given unless there is severe liver damage. If ascitis and portal hypertension are present, treat with 2 SHE / 10 HE. In case of acute hepatitis, the treatment may be deferred. If TB is serious, treat with 3 SE or 3 SE + ofloxacin followed by 6 HR when hepatitis is recovered.
What to do if jaundice develops in a case during treatment?
Stop all drugs and monitor serum transaminases. Usually treatment can be re-started with the same regimen after the serum levels of transaminases return to normal. In serious cases, Ethambutol and Streptomycin which are least hepato-toxic can be given.
How to treat TB patients also suffering from Renal Failure?
Drugs eliminated by non-renal routes – INH, Rifampicin, Pyrazinamide and Thioamides may be given in normal doses. 2 HRZ / 4 HR is safe. Decrease dose of Streptomycin & Ethambutol and adjust by renal function tests.
What are the general guidelines for treatment among HIV positive TB patients?
Same regimen is used, as for HIV negative TB cases, since sputum conversion rates and cure rates are similar if effective chemotherapy is given. However, the treatment in Continuation Phase should also be fully supervised since lower rates of adherence and higher fatality rates have been observed among such patients.