Successful therapy of microbial infections depends upon several factors viz. identification of pathogens and their drug sensitivity, rapid attainment of effective drug concentration at the site of infection, host defenses and maintenance of drug level for adequate period, use of supportive drugs and duration of treatment.
The therapeutic concentration of drug at focus of infection is however, based on its dosage form, dosing rate, route of administration penetrating power, distribution and rate of elimination, chemical characters and physico-chemical properties.
The absorption and disposition of drugs in the body are influenced by chemical characters and physico-chemical properties of the drug. Bacterial sensitivity, pharmacokinetic properties and dosing rate of the drug ultimately decide the outcome of therapy.
Success of Chemotherapy:
Successful therapy is based on firm laboratory diagnosis.
1. Samples for bacteriological investigation is taken before administering drugs.
2. It is necessary to isolate and identify the pathogen and determine its sensitivity.
3. Clinical symptoms and disk diffusion mainly decide the selection of drug.
4. In addition selection of drug is also dependent on knowledge of the factors affecting drug concentration at the focus of infection, drug toxicity, cost of the treatment and withdrawal times.
Based on the clinical responses of the patient:
1. Laboratory reports are evaluated for the desirability of changing the drug regimen.
2. Some organisms are uniformly susceptible to certain drugs. If they are isolated, they are not tested for drug sensitivity e.g. pneumococci, streptococci and clostridia respond well to penicillins.
3. In Gram-negative bacteria drug sensitivity report is important because they readily acquire transferable resistance.
4. Agar disk diffusion test is routinely performed in veterinary practice.
Discrepancies between the disk test results and clinical response are due to:
(i) Failure in isolating the causative agent,
(ii) Mishandling of specimens or swabs during transit,
(iii) Failure in draining pus or foreign body,
(iv) Poor penetrating power of the drug,
(v) Super infection,
(vi) Mixed infections and
(vii) Emergence of drug resistant mutants.
Tips to Clinicians:
(i) Bactericidal drugs are advocated in immuno-deficient animals, whereas bacteriostatic agents may be prescribed in other cases.
(ii) The isolates of E. coli from bovine mastitis and piglet diarrhoea from the same region show variation in drug sensitivity. Similarly, isolates from different regions vary in their sensitivity (Soman, 1999). Physicians should, therefore, be familiar into the drug sensitivity pattern of the causative agents of the area.
(iii) Clinicians should be familiar not only with the individual diseases of animals but also with their differential diagnosis and relative prevalence in their areas.
(iv) They should know the organisms producing similar symptoms. For initial therapy broad spectrum drug is advocated. As mastitis is caused by different organisms and clinician is not sure about the causes, it is advocated to initiate therapy with a broad spectrum antimicrobial or a combination of drugs.
(v) In cases, where foci of infection or causative agents are not determined by clinical examination e.g. abscesses in internal organs, treatment is initiated with broad spectrum drugs.
(vi) In out-breaks, the etiological identification is essential for selection of drugs and future course of action for the control of the disease.
(vii) Prolonged therapy and oral feeding of antibiotics may develop resistant organisms. These organisms can pass from one species to another and colonize. E. coli and Salmonella spp develop complex multiple resistance. In such cases sensitivity test is essential to select suitable drugs for treatment.
(viii) Status of the host e.g. age, genetic factor, pregnancy and lactation determines the selection of the drugs and clinical outcome.
(ix) Normal host defence mechanisms hasten the recovery and favour fruitful outcome of drug therapy. Defensive mechanisms are not normal in young ones and aged animals.
(x) Presence of pus in lesions and acidic condition in abscess cavity reduces the activity of aminoglycosides, whereas, acidic pH favours the action of chlortetracycline, nitrofurantoin and methenamine.
(xi) Infectious agent in phagocytic cells is protected from antimicrobial action.
(xii) Streptomycin and tetracyclines are not advocated in pregnant animals.
(xiii) Similarly sulfonamide therapy is not favoured in lactating animals.
Antimicrobial agents that are lipophilic can easily penetrate most tissues of the body and infectious foci. Lipophilic agents are erythromycin, trimethoprim, chloramphenicol, metronidazole and rifampin. Lipid solubility of tetracyclines varies with the compounds.
Antimicrobial drugs are weak organic electrolytes either acids or bases with exception of tetracyclines, rifampin and chloramphenicol which are amphoteric, zwitterion and neutral respectively.
Penicillins and sulfa drugs are weak organic acids whereas aminoglycosides, macrolides and trimethoprim are bases.
Passive diffusion of drugs across cell membrane depend on lipid solubility. Non ionized drug forms are lipid soluble.
Distribution pattern of a drug is determined by the blood flow to tissues. Drugs penetrate mostly by passive diffusion.
Formulations of the preparations may influence both the rate and extent of absorptions. Sustained release forms provide slow continuous absorption at a rate that maintains effective plasma concentration of the drug for the duration of the recommended dosing interval.
Duration of Treatment:
It becomes clear within 2 days whether the therapy is effective. If no response observed, both the diagnosis and treatment should be reconsidered. Therapy should be continued for 3-5 days or even longer depending on the type of infections (acute or chronic). Treatment is continued for at-least one day beyond the return of normal body temperature. For serious infections treatment is continued for 7-10 days.
Failure of Antimicrobial Therapy:
Several causes of drug failures are:
(i) Failure of isolation and identification of specific cause of the disease.
(ii) Lack of proper selection of drugs due to misdiagnosis.
(iii) Inappropriate results of laboratory tests.
(iv) Resistant organism as cause of the infection.
(v) Intracellular location of the parasites.
(vi) Errors in sampling.
(vii) Inadequate drug dose and incorrect route of administration.
(viii) Impairment of host defense because of corticosteroid treatment or some other factors.
(ix) Non-compliance of dosing instructions.
(x) Presence of foreign bodies or necrotic material in the host causing inactivation of aminoglycosides and sulfa drugs.
Incompatibilities:
Antimicrobial drugs may interact physicochemical to many other agents. Harmful interaction may occur without visible change. It is advisable not to mix them in the same syringe.
Most drugs can be mixed in normal saline with exception of benzyl penicillin and sodium ampicillin. Similarly tetracyclines are not mixed with any solution containing calcium or magnesium. Penicillin-G, chloramphenicol and tetracycline should not be mixed because they precipitate.
Withdrawal:
There is specific regulation for withdrawal of drugs used in feeds for animal meant for slaughter. Drugs should not be present in animal derived foods for human consumption.
Specific withdrawal period is allowed for antimicrobials before slaughter or milk of treated animals used for human consumption. For injectable preparations, withdrawal times are given in Table 25.2. Similarly withholding times for intra-mammary preparations are depicted in Table 25.3.
Adverse Effects:
An ideal antimicrobial drug should be free from host toxicity.
Antimicrobial drugs in common use, however, cause one or the other following damaging effects:
(i) Direct host toxicity (aminoglycosides)
(ii) Adverse interactions with other drugs
(iii) Interference with the protective effect of normal host microflora or disturbance of metabolic functions of microflora of digestive tract of herbivores
(iv) Selection or drug resistance
(v) Tissue necrosis at injection site
(vi) Production of drug residues in animal products for human consumption and
(vii) Impairment of host immune systems (tetracyclines, aminoglycosides) and
(viii) Hypersensitivity (allergy) reactions e.g., fever, rash and anaphylaxis.
