Principles of Antimicrobial Therapy

[Kvet Forum]

The success of antimicrobial therapy depends on attaining and maintaining, at the site of infection, a drug concentration that will result, directly or indirectly, in the death or control of the infectious organism with minimal deleterious effect to the host. To achieve these aims the antimicrobial agent must have activity against the organism at its site of infection and it must be administered in such a way as to maintain an effective inhibitory or lethal concentration. These principles apply to therapy in all species and dictate the choice of antimicrobial agent to be used. However, in farm animal veterinary practice there are also other important considerations:

• Cost is critical. This consideration includes not only the primary cost of the drug but also related factors such as the ease and frequency of administration and the duration of treatment.
• Tissue residue problems and withdrawal periods must also be taken into consideration and are a primary determinant of treatment strategy.
• Animal welfare becomes a consideration when a decision is made not to treat an animal because of concerns about cost or the occurrence of residues that would preclude marketing of the animal or its products in the future.
• Antimicrobial resistance and the risk of contributing to the emergence and problem of antimicrobial resistance is an increasing concern, not so much with the therapeutic use of antimicrobials but certainly with the prolonged administration of antimicrobials in animal feeds for disease prevention.

In the theoretically ideal situation, the following steps would be taken before selecting an antimicrobial agent for therapy:

• First, the site of infection would be located and the identity of the infecting organism established by culture.
• Second, the minimal inhibitory concentration (MIC) of each antimicrobial agent for the infecting organism would be identified.
• Third, an initial selection would be made based on the susceptibility of the organism and the knowledge of the capacity of the individual antimicrobial agents to penetrate the site of infection and to achieve and exceed these concentrations at nontoxic dose rates.
• Fourth, the dose rates, route of administration, and frequency of administration required to achieve these concentrations for each of the selected antibiotics, in the particular animal species being treated, would then be considered.
• Finally, selection of a particular drug would be based on a consideration of the potential toxicity to the host, on the likely relative efficiency of each drug, on the cost and ease of administration and, in food animals, on costs associated with the relative withholding periods.

For many clinical situations all of these steps cannot be followed before therapy is instituted. It may take several days to establish the identity of the infectious agent.

Additionally, knowledge about each antimicrobial agent and of the varying tissue and organ levels achieved following varying doses given by different routes of administration is not easily remembered and, therefore, not easily available in field situations. Unfortunately, complete information of this type also is not available for each antimicrobial agent.

Because of this uncertainty, some expedients are adopted in clinical antimicrobial therapy. One of them is the concept of the recommended dose. Regardless, it should be recognized that rational antimicrobial therapy is based upon the principles outlined above.