Management of Tuberculosis: Therapeutic Approach

Pulmonary tuberculosis (Tuberculosis of lungs) or Extra-pulmonary tuberculosis (Tuberculosis of organs other than lungs) in humans is caused by Mycobacterium tuberculosis, a human tubercle bacillus. Mycobacterium tuberculosis is an obligate anaerobic bacterium, whose natural reservoir is human beings. Mycobacterium tuberculosis (MTB) is non-motile and does not produce spores. The generation time of MTB is 15 to 20 hours, so it is also called slow growing bacterium.

Tuberculosis (TB) of any type remains a challenging clinical problem and important public health issue the world over. In the recent past the World Health Organization (WHO) has documented an annual incidence of 9.27 million new cases of TB with a prevalence of 13.7 million cases. Majority of TB cases exist in Africa and South East Asia. The annual incidence rate in Africa and South East Asia has been reported as 356 and 182 cases per 100,000 population respectively that is much higher than the global incidence rate.

The ‘gold standard’ in the diagnosis of TB has been the detection of Mycobacterium tuberculosis in the sputum smear or in the pathological lesions (by histopathological methods). The rapid diagnosis of TB is fundamental to clinical outcome. On general physical examination careful attention should be given to the presence of lymphadenopathy (swollen/enlarged lymphnodes), draining sinuses, non-healing ulcers, spinal or joint lesions etc.

Extensive research has been going on in the field of management of TB through anti-tubercular treatment (ATT) ever since the discovery of rifampicin in 1960s. The major objectives of research in anti-tubercular treatment (ATT) include the shortening of duration of therapy, preventing the emergency of drug resistance, avoiding toxicity and shortening the period of infectivity. Direct Observation Therapy-Short Course (DOTS) is the most effective strategy propagated for the management of tuberculosis. Several new drugs and non-pharmacological therapeutic modalities are under extensive study for the effective management of tuberculosis.

A)  Pharmacological Approach to Management of TB:

Pharmacological drugs can be classified as

Ø  Drugs susceptible for MTB.

Ø  Drugs susceptible for conventional ‘drug-resistant bacilli’, which include the followings:

·         Re-purposed drugs (e.g. Fluoroquinolones)

·         New dosages of already available drugs (e.g. Rifampicin rifamycin or high dose isoniazid)

·         New drugs (e.g. Bedaquiline for ‘multi drug resistant-TB).

B)  Preventive Approach to Management of TB:

Ø  Vaccination: The use of BCG vaccination is recommended. Recombinant BCGs are also under clinical trials.

Ø  Chemoprophylaxis for Latent-TB: Chemoprophylaxis is recommended for new born babies born to ‘sputum smear positive’ mothers. Chemoprophylaxis should also be recommended for the cases having ‘Latent-TB’. Interferon gamma release assay test (IGRAs) and Mantoux Test (a Skin Test) are useful tests for establishing a diagnosis of Latent-TB. However, these tests do not necessarily indicate the presence of active tuberculosis and requirement of ATT.

C)  Non-pharmacological Approach to Management of TB:

Ø  Non-pharmacological advances are based on immunomodulation and immunotherapy. Use of protective cytokines, anti-cytokine agents (such as thalidomide pentoxiphylline) and immune-enhancement with ‘heat killed Mycobacterium vaccine’ and other recombinant BCGs have been under clinical trials. These modalities have not been recommended for standard clinical practice.

Ø  Strategies for Airborne Infection Control:  ‘International Guidelines on Airborne Infection Control in Healthcare Settings’ should be adopted. These guidelines are very important in the isolation wards, multi-drug resistant-TB (MDR-TB) wards and the Medical Laboratories conducting TB tests, for prevention of spread of infection among health workers in hospitals.

 

 

Usage of Antibiotics in Pediatric Practice

Antibiotics are very potent weapon to kill a variety of bacteria, but should be used judiciously to avoid life threatening complications. Attempts to treat symptoms of infections without identifying the bacteria or site of infection could be very harmful in infants and children. Selection of antibiotic and its optimal use is the key to effective treatment. There is a need to understand the pharmacologic principals to select an antimicrobial agent and to avoid allergic reactions and toxicity in the patient being treated. The penetration and diffusion of antibiotics in various tissues and spaces should be taken into account while deciding the dose and mode of administration of an antibiotic. All antibiotics cannot treat pyogenic meningitis and purulent exudates. Antibiotics could be classified into three groups for treatment of infectious agents in infants and children:-

1. Penicillins: Ampicillin, amoxicillin, penicillinase, penicillin G &V.
   
2. Alternative of penicillin for patients allergic to penicillin: Cotrimoxazole, erythromycin, tetracyclines, lincomycin etc.
   
3. Antibiotics effective against Gram-negative bacteria: Gentamycin, kanamycin, tobramycin, amikacin etc.
   

Situations where antibiotics should be avoided:

1. Viral infections: Usually viral infections are self limiting and the patient may recover within a week's time. Use of antibiotics for the treatment of chickenpox, measles, mumps and viral URI (upper respiratory infection). However, antibiotics may be helpful in controlling/preventing secondary bacterial infections during viral infections.
   
2. Treatment of pyogenic exudates without surgical drainage: Extensive use of antibiotics to treat purulent exudates without surgical drainage should be avoided since the infection will not come under control without drainage.
   
3. Improper dosage: Both the suboptimal and large doses of antibiotics are harmful and should be avoided.
   
4. Prophylactic use of antibiotics: Antibiotics should be used to treat established disease only and not as prophylactic therapy to prevent infection in patients/children at high risk. However, chemoprophylaxis is helpful in preventing the spread of singe microorganism with single drug but to use multiple antibiotics for prophylaxis could be hazardous.