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Non Judious Use of Antibirobials; A Root Cause of Antibiotic Resistance

  • Antibiotics play an important role in the treatment of various infectious diseases in man and domestic animals. In treating microbial infection, it is essential that an effective concentration of an antibacterial drug be rapidly attained at the focus of infection and maintained for an adequate time. The concentration achieved varies with systemic availability of the drug based on its dosage form, dosing rate, routes of administration and ability to gain access to the infection site. The concentration also varies with the physicochemical characteristics of the drug, which subsequently influence the extent of absorption, patterns of distribution and elimination mechanisms. Microbial susceptibility to the drug concentration is also critical aspect for clinical efficacy of an antibiotic. Thus, effective therapy depends on a triad of bacterial susceptibility, pharmacokinetic characteristics of the drug and dosing rate.

    The Asian countries have varying topographical and environmental conditions under which a considerable number of livestock and poultry are growing. The knowledge relating to health, disease and husbandry of these animals is acquired usually from the literature of the western countries where the environmental conditions, the genetic make up of man and animals and nutritional conditions are different from those of the Asian countries.
    Most of the developing countries like Pakistan are importing raw or finished drugs for their human and veterinary health programs. Drug developments supported by extensive preclinical and clinical investigations are carried out in the drug exporting countries. In most cases the genetic make up of man and animals and environmental conditions are different amongst the drug importing and exporting countries. Several studies have shown that the pharmacokinetics behavior, optimal dosage, renal clearance and urinary excretion of the investigated drugs were different under indigenous conditions when compared with the values given in the literature or in the product inserts supplied by the manufacturers. An original term “geonetics” has, therefore, been coined to describe the environmental influences on the genetics which are manifested by characteristic biochemical and physiological parameters which ultimately affect the biodisposition and fate of drugs in a population. Such geonetical influences have been reported for blood and urine pH, blood proteins, drug metabolism and kidney function in buffaloes, cows, sheep and goats. In view of these studies it may be hypothesized that biochemical milieu interieur and physiological parameters are influenced by geonetical conditions which ultimately affect the fate of drugs and are likely to affect the response to them. Several investigations in animal models have shown that biodisposition of certain drugs and antibiotics under indigenous conditions is different from the disposition recorded elsewhere. So, it would be rational that an optimal dosage regimen should be based on the pharmacokinetic data determined in the species and environment in which a drug is to be employed clinically.
    The fluoroquinolones are a series of synthetic antibacterial agents which are used in the treatment of a variety of bacterial infections. Over the last two decades, research on these antimicrobials has produced some very potent agents, like ciprofloxacin, which are equally effective against both gram positive and gram negative bacteria. In the experiments conducted in our study, different parameters of ciprofloxacin were evaluated in local buffaloes, cows, sheep and goats under local environmental conditions. ciprofloxacin was injected intramuscularly in these animals at the dose rate of 5 mg/kg body weight and data obtained was analyzed to calculate optimal dose of this antimicrobial. The results revealed highly significant difference between the calculated dose and the dose recommended by the manufacturer. Dose calculated in local animals was almost four times higher than the recommended dose. This situation is alarming as if the drug is continuously used at its foreign recommended dosage level, it will not attain its minimum inhibitory concentration in the body which is necessary to kill the bacteria responsible for the disease. At this lower level, the bacteria may develop some defense mechanisms to counter the effect of these antimicrobials and become resistant. When the same antibiotic is used even at very high level afterwards, these resistant bacteria are not killed or eradicated due to the pre-developed resistance. This may also result in emergence of modified strains of the bacteria which may be resistant to most of the existing antibiotics and antibiotic failure will be the end point. Ultimately these ever resistant strains may also be transferred to the human beings and human diseases will become incurable like MDR-TB where almost no antibiotic is effective against tuberculosis. Alternative to this situation is the development of new drugs, which costs very high and is almost unaffordable for the developing countries like Pakistan.
    As the whole dilemma is due to under dose of the antibiotics, so, may be overcome by using these antibiotics at the higher dose levels and it is only possible when we calculate the doses of the antibiotics in our local species and under local conditions otherwise we must prepare our minds to face the era when no antibiotic will remain effective even against the minor infections and diseases will become incurable.

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