Vancomycin: the tale of the vanquisher and the pyrrhic victory

Vancomycin has been the antibiotic of choice in the treatment of methicillin-resistant Staphylococcus aureus infections for decades. But relatively recently, vancomycin-intermediate-susceptible S. aureus (VISA) have been reported. Phenotypically, VISA are characterized by thicker cell walls, requiring higher concentrations of vancomycin for inhibition of bacterial cell growth. Vancomycin-intermediate-susceptible S. aureus represent just the tip of the iceberg of an insidious loss of vancomycin susceptibility in staphylococci. Increasing proportions of S. aureus isolates have higher minimum inhibitory concentrations that are still within the officially susceptible range, a characteristic that is associated with treatment failure. The most important risk factor for decreased vancomycin susceptibility is in vivo selection pressure. To prevent the development of VISA, prolonged or inappropriate use of vancomycin and suboptimal vancomycin levels should be avoided. Trough serum vancomycin concentrations of 15 - 20 mg/L for intermittent dosing and plateau serum vancomycin concentrations of 20 - 25 mg/L for continuous infusions are therefore currently recommended. The widespread clinical application of these intensive dosing regimens has resulted in an increasing awareness of vancomycin-induced nephrotoxicity, which is especially relevant in patients whose renal function is already compromised. This narrow therapeutic-toxic window reinforces the use of rigorous dosing protocols. In hemodialysis, the use of a vancomycin dose calculator permits achievement of target concentrations in most patients. In peritoneal dialysis (PD), intermittent vancomycin dosing regimens often lead to low end-of-dwell concentrations. On the other hand, a continuous vancomycin dosing regimen after a loading dose offers the desired combination of high local levels without toxic systemic levels.