Enhancement or inhibition of antimicrobial activity in serum by metabolic alterations in disease

Abstract

Protein binding is an important determinant of antimicrobial activity in serum. Disease states can alter the binding of antimicrobials and thereby affect their biologic activity. Uremia is associated with a reduction in the binding of dicloxacillin, penicillin G, cefamandole and cefalothin with a resulting enhancement in antimicrobial activity as measured by agar diffusion zones of inhibition or minimal inhibitory and bactericidal concentrations. The greatest change is observed with the more avidly bound dicloxacillin. Free fatty acids (FFA) decrease the binding of dicloxacillin and cefamandole, but enhance the binding of penicillin G and cefalothin. These contrasting effects of FFA on protein binding are also reflected by changes in antimicrobial activity in serum. These metabolic alterations of protein binding in disease may also affect antimicrobial activity in vivo.