Treatment of Methicillin-Resistant Staphylococcus aureus (MRSA) Infections in Children: a Reappraisal of Vancomycin

Abstract

Purpose of review: In the last 50 years, vancomycin has been the agent of choice to treat infections due to methicillin-resistant Staphylococcus aureus (MRSA). However, vancomycin treatment failure is not uncommon, even when MRSA strains are fully susceptible to vancomycin. Treatment with vancomycin requires careful monitoring of drug levels as there is a potential for nephrotoxicity. Resistance to clindamycin is not infrequent, which also limits therapeutic options for treating infections due to MRSA in children. This paper reviews the current data on pharmacokinetics and pharmacodynamics and clinical efficacy of vancomycin in children.

Recent findings: Resistance to vancomycin in MRSA (MIC >2 mg/L) is infrequent; there is increasing evidence in the literature that vancomycin maybe ineffective against increasing proportion of isolates with MICs between 1 and 2 mg/L. Recent studies and meta-analyses have demonstrated that strains with high vancomycin MICs are associated with poor outcomes especially in patients with bacteremia and deep tissue infections due to MRSA. This gradual increase in vancomycin MIC has been reported as MIC creep or vancomycin heteroresistance. Patients infected with MRSA isolates that exhibit MIC creep experience poorer clinical outcomes, including delayed treatment response, increased mortality, increase rate of relapse, and extended hospitalization. There are limited data to guide vancomycin dosing in children with MRSA. Although the vancomycin area under the curve AUC₂₄/MIC ratio > 400 has been shown to predict clinical efficacy in adults, this relationship has not been documented very well for treatment outcomes in MRSA infections in children. Use of higher vancomycin dosages in attempts to achieve higher trough concentrations has been associated with increased nephrotoxicity. New recently approved antibiotics including ceftaroline, dalbavancin, and tedizolid offer a number of advantages over vancomycin to treat staphylococcal infections: improved antimicrobial activity, superior pharmacokinetics, pharmacodynamics, tolerability, and dosing, including once-daily and weekly regimens, and less need for monitoring drug levels.

Keywords: AUC24/MIC; Heteroresistance; MRSA; Nephrotoxicity; Staphylococcus aureus; Vancomycin.