263 Vancomycin minimum inhibitory concentration (MIC) creep among methicillin-resistant Staphylococcus aureus (MRSA): A literature review

Saturday, April 2, 2011
Trinity Ballroom (Hilton Anatole)
Jarrett Amsden, PharmD , Butler University, Indianapolis, IN
Iftekhar Kalsekar, PhD , Butler University, Indianapolis, IN
Smita Kothari, PhD, MBA , Astellas Pharma US, Inc, Deerfield, IL
Andrew Shorr, MD, MPH , Washington Health Center, Potomac, MD
Marya Zilberberg, MD, MPH , EviMed Research Group, LLC, Goshen, MA
Background: MRSA poses a considerable public health problem. While vancomycin-resistant S. aureus (VRSA) are rare, there have been reports of rising MICs for vancomycin among MRSA. Some studies report worse outcomes with higher MICs, but clinical significance has been variable.

Objective: We examined the literature on the relationship between vancomycin MICs for S. aureus and clinical outcomes.

Methods: Search for English language articles in the EMBASE and MEDLINE electronic database for terms MRSA, MIC, vancomycin and outcomes was conducted.  Comprehensive review of studies reporting outcomes associated with vancomycin MIC elevation among MRSA is presented.

Results: We identified 17 studies investigating vancomycin MIC elevations. Higher vancomycin MIC values have been associated with worse patient outcomes, specifically with increased rates of vancomycin treatment failures (range: 36-51%), increased hospital length of stay (LOS) (range: 19-24 days), and in some studies, an increase in mortality (range: 18-28%). Additionally, treatment failures and LOS have led to increases in total hospital costs. Poor outcomes associated with increased vancomycin MICs  have resulted in lowering of the vancomycin susceptibility break-points for MRSA. At the same time, studies testing higher doses of vancomycin did not find any outcome advantages. Furthermore, an increased incidence of nephrotoxicity has been associated with higher doses of vancomycin.   

Conclusions: Increased vancomycin MICs for MRSA are  associated with worse patient outcomes and have been established in multiple studies, leading to the lowering of susceptibility thresholds for vancomycin. Increasing vancomycin doses to overcome increased MICs have not improved outcomes and have resulted in increased nephrotoxicity risk. Judicious and appropriate use of vancomycin is needed in order to stem MRSA’s march toward vancomycin resistance. Newer anti-MRSA therapies need to be evaluated and used appropriately in order to preserve their activity against this highly resistant pathogen. Clinicians and investigators need to be vigilant for emergence of resistance to vancomycin and newer emerging therapies.