Chapter 69

Antimicrobial-Associated Diarrhea

Claire H. Stratford, Bruce C. McGorum

Antimicrobial-associated diarrhea (AAD) is the most common adverse effect associated with antimicrobial use in horses. The condition ranges in severity from mild self-limited diarrhea to an often fatal acute toxic enterocolitis. It is associated with significant increases in duration of hospitalization, treatment costs, and mortality rate. Although nearly all oral and parenteral antimicrobials have been associated with AAD, certain antimicrobials anecdotally appear to pose a greater risk.

Antimicrobial-associated diarrhea is defined as acute-onset diarrhea that is temporally associated with antimicrobial administration for non–gastrointestinal-related purposes and is otherwise unexplained. However, although AAD may be suspected, a definitive causal link cannot usually be established in clinical practice, and much of the related literature is based on anecdotal opinion.

Risk Factors

Antimicrobial Based

Although certain antimicrobials are anecdotally associated with an increased frequency of AAD, all are capable of inducing AAD. The ability of different antimicrobials to induce AAD appears mostly dependent on their effect on enteric anaerobes. This is influenced by the dose and route of administration, the resultant “active” concentration of antimicrobial in the intestinal lumen (increased in antimicrobials with poor oral bioavailability and those that undergo enterohepatic or biliary recycling), and the drug’s spectrum of activity against anaerobes. For example, antimicrobials with poor efficacy against anaerobes, such as trimethoprim-sulfonamides, fluoroquinolones, and aminoglycosides, appear less likely to result in AAD than those with high efficacy against anaerobes, such as macrolides, lincosamides, β-lactams, and tetracyclines. Both orally and parenterally administered antimicrobials are capable of inducing AAD, and the risk is potentially increased by the combined use of antimicrobial classes.

Host Based

AAD can affect all ages and both sexes of horses. However, AAD is thought to be less prevalent in suckling foals, possibly because of the increased oral bioavailability of antimicrobials in foals and their underdeveloped intestinal microflora, compared with adults. Additionally, AAD in foals is often mild and resolves quickly after withdrawal of antimicrobials.

The etiology and incidence of AAD appear to differ geographically; this may reflect differences in intestinal carriage of potential pathogens (e.g., Clostridium difficile, Clostridium perfringens, Salmonella spp), their toxigenicity, and their antimicrobial sensitivity patterns. The risk for AAD is also increased by concurrent stressors such as transportation, hospitalization, and associated exposure to nosocomial infection and hospital-based strains of antimicrobial-resistant bacteria.

Pathogenesis

The resident gastrointestinal microflora is a delicate balance of numerous bacterial species, with a predominance of strict anaerobes. This microflora population has important roles in microbial digestion, regulation of fluid and ion transport across the large colon, and prevention of colonization by pathogens, termed colonization resistance. The pathogenesis of AAD is likely complex and multifactorial, resulting from antimicrobial-mediated alteration of this resident gastrointestinal microflora, and causing the following: