Vancomycin is a complex glycopeptide that binds to precursors of the peptidoglycan layer in bacterial cell walls. This effect prevents cell wall synthesis and produces a rapid bactericidal effect in dividing bacteria. Its efficacy is time dependent. Vancomycin is active against most gram-positive aerobes and anaerobes but is not effective against gram-negative cells because of their large size and poor penetrability.
Vancomycin's spectrum includes Clostridia, Staphylococci (including beta-lactamase and methicillin-resistant strains), and Enterococci. Because of its efficacy against multidrug-resistant bacteria and critical importance to human medicine, use of vancomycin should be limited to multidrug-resistant gram-positive infections causing life-threatening systemic disease. Resistance to vancomycin does not readily develop but is an emerging problem as its use has increased.
In countries where avoparcin (a vancomycin analogue) was used as a growth promoter in production animals, vancomycin-resistant enterococci (VREs) have been found in the animals' commensal microbiota and edible tissues. Since avoparcin has been discontinued for this use, the prevalence of VREs in production animals has decreased. Reported in a variety of domestic animals, VREs exist due to acquired vancomycin resistance genes, such as vanA and vanB, or via plasmid-associated elements.
Oral absorption of vancomycin is poor, and the drug tends to stay within the GI tract, making this route acceptable only for the treatment of local infections, such as Clostridium difficile. However, after administration IV, vancomycin is widely distributed in the body, with a volume of distribution of 0.4–5.5 L/kg in dogs. Vancomycin is low to moderately protein-bound (10%–50%). Vancomycin is able to penetrate inflamed meninges and obtain appropriate CSF concentrations but does not achieve appropriate concentrations otherwise. Excretion (in active form) is via the kidneys; in renal insufficiency, striking accumulations may develop. The plasma half-life in dogs is 2 hours and approximately 3 hours in horses.
The only indication for use of parenteral vancomycin is serious infection due to methicillin-resistant Staphylococcus aureus. Vancomycin appears to be synergistic with aminoglycosides. Febrile reactions and thrombophlebitis (because of tissue irritation) at injection sites may occur. Hypersensitivity reactions are seen infrequently, and vancomycin flushing syndrome (associated with histamine release) is a risk in humans with bolus infusion; therefore, vancomycin should be infused over a minimum of an hour.
Ototoxicity and nephrotoxicity may occur with treatment. Vancomycin increases the risk of nephrotoxicity when combined with amphotericin, cyclosporine, cisplatin, tacrolimus, and polymyxin. Vancomycin is incompatible with beta-lactam antimicrobials, fluoroquinolones, aminoglycosides, macrolides, propofol, anticonvulsants, corticosteroids, furosemide, and alkaline solutions and therefore should not be mixed with any of those compounds in solution.
A number of newer lipoglycopeptide derivatives (telavancin, dalbavancin, and oritavancin) have emerged in human medicine that were designed to increase antibacterial activity, in some cases via secondary mechanisms of action. There are no data on the use of these drugs in veterinary species at this time, and therefore these drugs should be reserved for human medicine.
In the US, glycopeptides are prohibited from extralabel drug use (ELDU) in all food-producing animal species. Because there are no glycopeptides approved for veterinary use in the US, glycopeptides are prohibited from use in production animal species.
