CVC Highlights: Optimizing antimicrobial therapy

Robert L. Bill, DVM, MS, PhD, Basic Medical Science, School of Veterinary Medicine, Purdue University, West Lafayette, IN 47907.

To reduce the potential for developing bacterial resistance, it is important to follow treatment guidelines that help ensure elimination of the microbial population. The primary principle of successful antimicrobial therapy is to establish an adequate concentration of an antimicrobial that the organism is susceptible to at the infection site. Prudent antimicrobial selection includes correctly identifying the therapeutic needs of the animal (e.g. bacterial vs. viral infection), adjusting therapy in accord with the physiological state of the animal (e.g. bacteriostatic drugs rely on an animal's intact immune system to eliminate the pathogen), and understanding the drug's characteristics (e.g. aminoglycosides won't penetrate tissues with cellular barriers). Failure to consider all these factors can result in therapeutic failure or potentially severe adverse reactions.

Robert L. Bill, DVM, MS, PhD

When treating bacterial infections, keep in mind that if the inflammatory reaction to the primary pathogen has caused marked pathology, antimicrobial therapy alone may not alleviate the clinical condition. For example, a patient may become hypoxemic and die of pulmonary edema that arises secondary to inflammation associated with the bacterial infection. With few exceptions (e.g. sulfasalazine), antimicrobials will not directly reduce inflammatory components of disease. Treating the clinical signs in the short term may be as important as eliminating the infection.

In general, antimicrobials can be classified into three tiers. The antimicrobials in the first tier, or first line of defense, are selected based on whether the infections are empirically susceptible to commonly used older antimicrobials that have a narrower spectrum of coverage (compared with second- and third-tier drugs). These drugs include amoxicillin or amoxicillin with clavulanate, first-generation cephalosporins, trimethoprim-sulfadiazine, and tetracyclines.

The second-tier antimicrobials are selected based on an antimicrobial's extended spectrum of coverage (compared with first-tier drugs) and are reserved for those infections likely to be resistant to first-line drugs. Drugs included in the second tier are second- and third-generation cephalosporins, fluoroquinolones, lincosamides, oxacillin, and aminoglycosides.

The third tier of antimicrobials is selected based on the need to reserve certain drugs because of their importance to animal or human health and to select drugs for those infections that are documented to be resistant to first- and second-tier drugs. Drugs included in this category are the extended-spectrum penicillins, vancomycin, and imipenem-cilastatin.

Acute infections are treated for three days after clinical signs resolve. For chronic infections, extend treatment for three to six weeks depending on the organism, the site of infection (e.g. whether the drug can readily reach the site), and an estimation of the physiological changes that have occurred at the infection site that may interfere with the antimicrobial's ability to work (e.g. increased permeability of the blood-brain barrier to hydrophilic drugs during active inflammation followed by reduced permeability as the inflammation subsides).

SUGGESTED READING

1. Morley PS, Apley MD, Besser TE, et al. Antimicrobial drug use in veterinary medicine. J Vet Intern Med 2005;19:617-629.

Attendees selected this highlight from CVC lectures. The original paper was published in the proceedings of the 2005 Central Veterinary Conference.