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Vancomycin

Revised CLSI breakpoints for Vancomycin in S. aureus and its correlation with therapeutic monitoring

Vancomycin is one of the most widely used antibiotics for the treatment of serious gram positive infections involving methicillin-resistant S. aureus (MRSA). However serum vancomycin concentrations are need to be monitored in a relatively narrow range to lessen the potential for nephrotoxicity and ototoxicity and to achieve therapeutic concentrations.

The summary of recent guidelines for vancomycin therapeutic monitoring by American Society of Health- System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists (SIDP) is as follows: 1

Monitoring of trough serum vancomycin concentrations to reduce nephrotoxicity is recommended for  

  • Patient receiving aggressive dosing targeted to produce sustained trough drug concentrations of 15–20 mg/L or

  • High risk of toxicity, such as patients receiving concurrent nephrotoxins.

  • Patients with unstable renal function   

  • Those receiving prolonged courses of therapy (over three to five days).

Monitoring serum vancomycin levels to prevent ototoxicity is not recommended

  • Because this toxicity is rarely associated with monotherapy and does not correlate with serum vancomycin concentrations.

  • Monitoring may be more important when other ototoxic agents, such as aminoglycosides, are administered.

Reference values:

  • AUC/MIC is a predictive pharmacokinetic parameter for vancomycin. AUC/MIC ratio of ≥400 is proposed as a target to achieve clinical effectiveness with vancomycin for the treatment of both methicillin susceptible S. aureus (MSSA), MRSA, and vancomycin-intermediate S. aureus (VISA) strains.

  • Trough serum vancomycin concentrations are the most accurate and practical method for monitoring vancomycin effectiveness.

  • Trough concentrations should be obtained just before the fourth dose in patients with normal renal function

  • It is recommended that trough serum vancomycin concentrations always be maintained above 10 mg/L to avoid development of resistance because there are evidence suggesting that S. aureus exposure to trough serum vancomycin concentrations of <10 mg/L can produce strains with VISA like characteristics.

  • For S. aureus with an MIC of 1 mg/L, the minimum trough concentration would have to be at least 15 mg/L to generate the target AUC: MIC of 400

  • To improve clinical outcomes for complicated infections such as bacteremia, endocarditis, osteomyelitis, meningitis, and hospital acquired pneumonia caused by S. aureus, total trough serum vancomycin concentrations of 15–20 mg/L are recommended.

Revised MIC  break points

 

 Minimum Inhibitory Concentration (MIC) (µg/mL)

 

Susceptible (S)

Intermediate (I)

Resistant (R)

Updated

≤2

4-8

≥16

Previous

≤4

8-16

≥32

 

 

 

 

 

 

The current current susceptibility breakpoints for glycopeptides have been reviewed by CLSI and  clinicians are encouraged to make sure that clinical microbiology laboratories with which they are associated are using the revised vancomycin susceptibility breakpoints for S. aureus.  

This revision is based on the following data.

  • Recently there are multiple reports of treatment failure in patients with infections caused by strains with MICs within the susceptibility range.2,3

  • Current CDC guidelines for testing S. aureus with vancomycin recommend that strains exhibiting MICs of 2 mg/liter plus growth on vancomycin screening plates are possibly VISA 4

  • Correct classifications of  VISA and hVISA would increase from 45% and 0% to 100% and 17.2%, respectively5

References:

  • Michael Rybak 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.

  • Fred C et al. The Rationale for Revising the Clinical and Laboratory Standards Institute Vancomycin Minimal Inhibitory Concentration Interpretive Criteria for Staphylococcus aureus. Clin Infect Dis 2007; 44: 1208–15.

  • Sakoulas,G et al.Relationship of MIC and bactericidal activity to efficacy of vancomycin for treatment of methicillin-resistant Staphylococcus  aureus bacteremia. J Clin Microbiol; 42: 2398–2402.

  • Mandy Wootton et al.  Evidence for Reduction in Breakpoints Used To Determine Vancomycin Susceptibility in Staphylococcus aureus. Antimicrob Agents Chemother 2009; 49: 3982-3.

 

Contribution...
Dr Saba Qaiser

 

 

 

 

 

 

 

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