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.
   

Usage of Steroids in Pediatric Practice

A child is not a compressed or mini man, so the method of scaling down the adult dose of a drug on the basis of body weight is not an accurate method for treating children. The pediatric pharmacology is a complex science since the drug requirements of neonates, older infants and children are quite different from adults due to difference in the absorption, biotransformation and renal excretion of drugs. Steroids are the most important drugs discovered after antibiotics. Though the steroids are not actual therapy but they provide immediate symptomatic relief. Steroids have been used both for their systemic action as well as topical actions. Steroids should not be misused and used only when indicated. Proper doses are very important for effective therapeutic effect.

In pediatric practice systemic use of steroids is indicated in many conditions. Three major dose related categories for systemic use of steroids are: (1) Replacement Therapy, (2) Therapeutic Doses (For treating hematological, renal and immunological disorders) and (3) Massive Doses (For treating hematological and renal disorders).

1) Steroids as replacement therapy:

Use of steroids as replacement therapy in congenital adrenal hyperplasia (CAH) and Addison's disease is very much indicated. The CAH is caused due to deficiency of 21-hydroxylase, so that 17-hydroxy progesterone is not converted into cortisol but is converted into adrenal androgens. Female babies with congenital adrenal hyperplasia (CAH) will be having ambiguous genitalia and male babies will show precocious puberty. The patients with CAH may also have mineralocorticoid deficiency. The other common type of CAH is represented by 11-hydroxylase deficiency and these patients are hypertensive and have masculinized looks. Both types of patients with CAH need replacement therapy with prednisolone (5mg/m² body surface area in two divided doses) or cortisone (20mg/m²body surface area in three divided doses). The dose of steroid is monitored by the estimation of 17-ketosteriod excretion, skeletal maturation and growth rate.

2) Therapeutic doses of Steroids :

Use of steroids is extremely indicated for treating hematological, renal and immunological disorders.

1. Use of Steroids in Hematological Disorders: Steroids have important role in the treatment of acute lymphatic leukemia, idiopathic thrombocytopenic purpura (ITP). Remission of acute lymphatic leukemia can be achieved with prednisolone (40mg/m² body surface area) within 4-6 weeks. However, success rate is around 80%. A success rate of around 95% is achievable if prednisolone is combined with Vincristine. In acute ITP steroids are the drug of choice to save life and are administered at a dose of 1-2mg/kg body weight for about 3 weeks or till the platelet count improves. Around 25% of patients may develop chronic ITP and may need steroid therapy (on alternate days) for about 3-6 months.
   
   


2. Use of Steroids in Renal Disorders: Treatment of nephrotic syndrome with steroids shows remarkable results. Prednisolone is given at a dose of 2mg/kg body weight daily for 4 weeks and the same dose is given at alternate days for another 4 weeks. Around 60-65% of patients show significant response in 4 weeks another 20-25% of cases will go into remission within 8 weeks of treatment. Around 8% cases may require prolonged treatment, while 3-5% may need other modes of therapy.
   
   


3. Use of Steroids in Immunological Disorders: Steroids remain the therapy of great importance in the treatment of Lupus nephritis, SLE, dermatomyositis, polyarteritis nodosa. Prednisolone is given at a dose of 2mg/kg body weight till the remission and then tapered off to minimum maintenance dose.
   
   


4. Use of Steroids in other diseases: Severe cases of asthma and status asthmaticus, where bronchodilators alone fail to control the disease; treatment with hydrocortisone and prednisolone is indicated. Steroids have been found to be useful in the treatment of ulcerative colitis. Acute cases of ulcerative colitis can be managed well with retention enema with steroids.
   
   

3) Massive Doses:

Massive doses of steroids are administered in patients affected by endotoxic shock. In these cases, steroids decrease the peripheral resistance, increase tissue perfusion and venous return. Such cases need Hydrocortisone in doses of 50-100mg/kg body weight initially and there may be need to repeat the dose 4-6 hourly for 24-48 hours. In 'rapidly progressive glomerulonephritis' (RPGN) and 'idiopathic apastic anemia' remarkable results have been achieved with higher doses of methyl prednisolone.

Understanding Drug Action, Interaction and Reaction

Monitoring of physical, cellular, biochemical, immunological and psychological parameter during the course of any drug therapy imparts us valuable information regarding drug action (expected relief), interaction (action in association dietary items and other drugs) and reaction (adverse effect of the drug or adverse drug reaction or ADR). Let us take the treatment of psoriasis, a chronic, immunological and inflammatory disease of skin for understanding drug, action, interaction and reaction. Psoriasis presents with erythematous, scaly (pustular) or indurated plaques over the extensor aspects of limbs, trunk, head and face and is widely treated with acitretin (synthetic aromatic analogue of retinoic acid).

Action of acitretin:

Systemic treatment with acitretin promotes cellular differentiation of epidermis and decrease proliferation rate in psoriatic plaques. It also exerts anti-inflammatory effect by modulating lymphocyte functions and inhibition of neutrophil migration. Psoriatic inflammation generally subsides within 6-12 weeks' period of treatment with acitretin. It is indicated for the treatment of moderate to severe psoriasis in adult patients. Pregnancy should be ruled out in female patients and they should be advised to use effective contraception at least for a period of three years to avoid pregnancy.

Interactions of acitretin:

• Acitretin interferes with the contraceptive action of minipill contraceptives and may result in failure of contraception.


• Use of alcohol during acitretin treatment should be avoided as ethanol converts acitretin to etretinate and thus prolongs clearance of acitretin.


• There is a risk of hypervitaminosis-A if acitretin is given along with vitamin-A.


• Risk of hepatitis increases if acitretin is administered in combination with methotrexate.


• Use of tetracyclines or its derivatives should be avoided in patients on acitretin therapy as there are chances of development of pseudotumor cerebri.


• Acitretin may decrease night vision, so patients should be advised to avoid driving at night.


• Acitretin should not be used in lactating mothers as it is excreted in the breast milk and may harm the baby as the drug is teratogenic.


• Acitretin sensitizes the skin to UV light so patient should be advised to avoid excessive exposure to sunlight.

Adverse drug reactions:

• Use of acitretin is contraindicated in pregnancy and during lactation. Fetal deformities like dysmorphia and cardiovascular malformations have been reported with the use of acitretin and/or etretinate.


• The drug has teratogenic.


• Commonly encountered adverse effects with acitretin are mucocutaneous effects like chelitis, xerosis, rhinitis, skin peeling over palms & soles, nail dystrophy, and hair loss.


• Dryness and irritation of eyes.


• Use of tetracycline or minocycline along with acitretin may lead to the development of pseudotumor cerebri.