HOME | CONTACT US
  
This online tutorial series "Quality Improvement: Tool Time" reinforces practical application of tools and competencies acquired during the live activity. Each Tool is a combination of faculty commentary on essentials in clinical practice, links to relevant scientific publications, and a printable handout that will serve as a reminder. Please select the topic:
  1. Ensuring Quality of Care 
    2.              
  2. Optimizing Vancomycin for MRSA Infections
    3.       
  3. Selecting Appropriate Therapy for ESBL- and KPC-Producers
    4.       
  4. Dosing Strategies for MDR P. aeruginosa/A. baumannii Infections
    5.       
  5. Adjusting Antimicrobial Regimens for Efficacy and Safety
    6.      

Optimizing Vancomycin for MRSA Infections
MRSA's Changing Epidemiology
The spread of MRSA has reached epidemic proportions in US hospitals. Approximately 60% of S. aureus isolates from hospitalized patients are methicillin-resistant. MRSA has also spread into the community and is now a major cause of community-acquired skin infections.

Impact of Increasing MRSA
Prevalence

Dr. Conan MacDougall discusses
vancomycin MIC creep

Increasing prevalence of MRSA has resulted in a significant rise in the use of vancomycin. From 2002 to 2006, a 43% increase in vancomycin use has been estimated in 22 US institutions. [1]
A potential consequence of increased vancomycin use is a trend towards decreased MRSA susceptibility to vancomycin, or “MIC creep”.
Though there is conflicting evidence for “MIC creep”, it is widely acknowledged that vancomycin effectiveness is reduced when the MRSA MIC is 2 μg/mL or higher. This makes it critical to

  1. optimally use vancomycin to maximize its effectiveness and safety
  2. recognize when an alternative agent is needed

MRSA isolates (%) with MIC=1 μg/mL [2]
Optimal Use of Vancomycin: IDSA, SIDP, and ASHP 2009 Guidelines [3]
If MIC≤1 μg/mL, vancomycin is the preferred agent
Target AUC/MIC
 400
Loading dose
 25–30 mg/kg
Trough serum vancomycin concentrations
 Obtained just before 4th dose
  • >10 μg/mL for all patients
  • 15–20 μg/mL for serious infections or if MIC=1 μg/mL
Dosage
 15–20 mg/kg q8–12h for most patients with normal renal function if MIC≤1 μg/mL
If MIC>1 μg/mL, use alternative agent

Vancomycin at Higher Doses: A Threat to Patient Safety?
For serious infections or if MIC=1 μg/mL, the guidelines recommend trough serum vancomycin concentrations above 15 μg/mL. However, this may come at the cost of increased toxicity. A study by Hermsen and colleagues showed that patients with higher trough serum vancomycin concentrations (>15 μg/mL) were 3-fold more likely to experience nephrotoxicity (31% vs. 10% respectively; P=.04). [4] Though confounding factors may have impacted this study with severely ill patients, clinical pharmacists should be aware of the potential for nephrotoxicity when maintaining higher trough serum vancomycin concentrations in their patients.

References

  1. Pakyz AL, MacDougall C, Oinonen M, Polk RE. Trends in antibacterial use in US academic health centers: 2002 to 2006. Arch Intern Med. 2008;168:2254-2260. Click here for complete article
  2. Wang G, Hindler JF, Ward KW, Bruckner DA. Increased vancomycin MICs for Staphylococcus aureus clinical isolates from a university hospital during a 5-year period. J Clin Microbiol.. 2006;44:3883-3886. Click here for complete article
  3. Rybak M, Lomaestro B, Rotschafer JC, et al. Therapeutic monitoring of vancomycin in adult patients: A consensus review of the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm. 2009;66:82-98. Click here for complete article
  4. Hermsen ED, Hanson M, Sankaranarayanan J, Stoner JA, Florescu MC, Rupp ME. Clinical outcomes and nephrotoxicity associated with vancomycin trough concentrations during treatment of deep-seated infections. Expert Opin Drug Saf. 2010;9:9-14.

Suggested Reading
Lodise TP, Graves J, Evans A, et al. Relationship between vancomycin MIC and failure among patients with methicillin-resistant Staphylococcus aureus bacteremia treated with vancomycin. Antimicrob Agents Chemother. 2008;52:3315-3320. Click here for complete article
This retrospective cohort study included 92 patients with MRSA bloodstream infection treated with vancomycin. Infections caused by isolates with high MICs (≥1.5 μg/mL) were associated with poorer outcomes compared with infections caused by isolates with low MICs (<1.5 μg/mL).

Mermel LA, Allon M, Bouza E, et al. Clinical practice guidelines for the diagnosis and management of intravascular catheter-related infection: 2009 update by the Infectious Diseases Society of America. Clin Infect Dis. 2009;49:1-45. Click here for complete article
These 2009 updated guidelines by the IDSA replace the previous 2001 guidelines. They offer evidence-based recommendations for clinical questions related to the diagnosis and management of catheter-related infections, including pathogen-specific management recommendations. For MRSA infections, vancomycin remains the treatment of choice, though linezolid and daptomycin can be considered as alternative agents.

Lodise TP, Patel N, Lomaestro BM, Rodvold KA, Drusano GL. Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. Clin Infect Dis. 2009;49:507-514.
This retrospective analysis was designed to determine the pharmacodynamic index that would best describe the relationship between vancomycin exposure and onset of nephrotoxicity. A total of 166 hospitalized patients who were given vancomycin to treat a Gram-positive infection were included. Analysis revealed that trough serum vancomycin concentration was the best indicator for predicting nephrotoxicity.