Therapeutic Monitoring Of Vancomycin For Serious Methicillin-Resistant Staphylococcus Aureus Infections

Therapeutic Monitoring

• 1

  In patients with suspected or definitive serious MRSA infections, an individualized target of the AUC/MIC BMD ratio of 400 to 600 (assuming a vancomycin MIC BMD of 1 mg/L) should be advocated to achieve clinical efficacy while improving patient safety. Doses of 15 to 20 mg/kg (based on actual body weight) administered every 8 to 12 hours as an intermittent infusion are recommended for most patients with normal renal function.

  AEvidence: IITreatment/Monitoring
• 2

  The most accurate and optimal way to manage vancomycin dosing should be through AUC-guided dosing and monitoring. This can be accomplished using 2 concentrations and first-order PK equations, or preferably, Bayesian software programs using 1 or 2 concentrations.

  AEvidence: IIMonitoring
• 3

  When transitioning to AUC/MIC monitoring, clinicians should conservatively target AUCs... targeted exposure should be achieved early during the course of therapy, preferably within the first 24 to 48 hours.

  AEvidence: IIMonitoring
• 4

  Trough-only monitoring, with a target of 15 to 20 mg/L, is no longer recommended based on efficacy and nephrotoxicity data in patients with serious infections due to MRSA.

  AEvidence: IIMonitoring
• 5

  Vancomycin monitoring is recommended for all patients at high risk for nephrotoxicity, patients with unstable renal function, and those receiving prolonged courses of therapy (more than 3 to 5 days).

  BEvidence: IIMonitoring

Vancomycin Susceptibility Testing

• 6

  For empiric dosing, the vancomycin MIC should be assumed to be 1 mg/L. When the MIC is <1 mg/L, we do not recommend decreasing the dose to achieve the AUC/MIC target.

  BEvidence: IIDosing

Continuous Infusion vs Intermittent Infusion

• 7

  Continuous infusion (CI) may be a reasonable alternative to conventional intermittent infusion dosing when the AUC target cannot be achieved. A loading dose of 15 to 20 mg/kg, followed by daily maintenance CI of 30 to 40 mg/kg to achieve a target steady-state concentration of 20 to 25 mg/L may be considered for critically ill patients.

  BEvidence: IIDosing
• 8

  The risk of developing nephrotoxicity with CI appears to be similar or lower than that with intermittent dosing when targeting a steady-state concentration of 15 to 25 mg/L.

  BEvidence: IISafety
• 9

  Incompatibility of vancomycin with other drugs commonly coadministered in the ICU requires the use of independent lines or multiple catheters when vancomycin is being considered for CI.

  AEvidence: IIIAdministration

Loading Doses

• 10

  In order to achieve rapid attainment of targeted concentrations in critically ill patients, a loading dose of 20 to 35 mg/kg can be considered for intermittent-infusion administration.

  BEvidence: IIDosing
• 11

  Loading doses should be based on actual body weight and not exceed 3,000 mg. More intensive and early therapeutic monitoring should also be performed in obese patients.

  BEvidence: IIDosing/Monitoring

Dosing in Obesity

• 12

  A vancomycin loading dose of 20 to 25 mg/kg using actual body weight, with a maximum dose of 3,000 mg, may be considered in obese adult patients. Empiric maintenance doses usually do not exceed 4,500 mg/day. Early and frequent monitoring of AUC is recommended.

  A/BEvidence: IIDosing

Renal Disease and Renal Replacement Therapies

• 13

  Provides specific loading and maintenance dose recommendations for intermittent hemodialysis based on dialyzer permeability and intradialytic vs. post-dialytic administration (e.g., loading 25-35 mg/kg, maintenance 7.5-15 mg/kg).

  BEvidence: IIDosing
• 14

  Since efficacy data are unavailable for AUC values of <400 mg·h/L, monitoring based on predialysis serum concentrations is practical. Maintaining predialysis concentrations between 15 and 20 mg/L is likely to achieve the AUC of 400 to 600 mg·h/L.

  CEvidence: IIIMonitoring
• 15

  For hybrid hemodialysis therapies, loading doses of 20 to 25 mg/kg actual body weight should be used. Maintenance doses of 15 mg/kg should be given after hybrid hemodialysis ends or during the final 60 to 90 minutes.

  BEvidence: IIIDosing
• 16

  For continuous renal replacement therapy (CRRT), loading doses of 20 to 25 mg/kg actual body weight should be used. Initial maintenance dosing should be 7.5 to 10 mg/kg every 12 hours.

  BEvidence: IIDosing

Pediatric Patients

• 17

  Initial recommended dosage for children with normal renal function is 60 to 80 mg/kg/day (divided q6h) for ages 3 months to <12 years, and 60 to 70 mg/kg/day (divided q6-8h) for >=12 years to achieve target AUC of 400-600.

  AEvidence: IIDosing
• 18

  AUC-guided therapeutic monitoring for vancomycin, preferably with Bayesian estimation, is suggested for all pediatric age groups.

  BEvidence: IIMonitoring
• 19

  Therapeutic monitoring may begin within 24 to 48 hours of vancomycin therapy for serious MRSA infections in children. Dosing adjustment should be made for renal insufficiency, obesity, or concurrent nephrotoxins.

  BEvidence: IIIMonitoring
• 20

  Vancomycin exposure may be optimally maintained below the thresholds for AUC of 800 mg·h/L and for trough concentrations of 15 mg/L to minimize AKI.

  BEvidence: IISafety/Monitoring
• 21

  Insufficient data exist on which to base a recommendation for a loading dose among the nonobese pediatric population.

  CEvidence: IIIDosing
• 22

  Obese children < 12 years old, compared with those >= 12 years, may require a higher mg/kg dose.

  BEvidence: IIDosing
• 23

  Therapeutic monitoring is likely to be of particular value in obese children. Recommendations for nonobese children may also apply.

  BEvidence: IIMonitoring
• 24

  A loading dose of 20 mg/kg by total body weight is recommended in obese children.

  AEvidence: IIIDosing
• 25

  Doses recommended to achieve an AUC of 400 mg·h/L in neonates and infants up to 3 months old range from 10 to 20 mg/kg every 8 to 48 hours depending on postmenstrual age, weight, and SCr.

  AEvidence: IIDosing

Therapeutic Area

Guideline Scope

Inclusion Criteria

• Serious invasive MRSA infections
• Bacteremia
• Sepsis
• Infective endocarditis
• Pneumonia
• Osteomyelitis
• Meningitis

Exclusion Criteria

• Methicillin-susceptible S. aureus (MSSA) strains
• Coagulase-negative staphylococci
• Nonbacteremic skin and skin structure infections
• Urinary tract infections

Care Settings

Special Populations

Evidence Levels

Recommendation Strength