Monitoring Vancomycin in Serious MRSA Infections

For the first time in 11 years, an updated consensus guideline on the therapeutic monitoring of vancomycin was recently published. The American Society of Health-System Pharmacists (ASHP), the Infectious Diseases Society of America (IDSA), the Pediatric Infectious Diseases Society (PIDS), and the Society of Infectious Diseases Pharmacists (SIDS) released a consensus guideline for monitoring vancomycin in the treatment of serious methicillin-resistant Staphylococcus aureus (MRSA) infections.

For years, vancomycin has been dosed according to dosing nomograms or pharmacokinetic (PK) parameters targeting a goal trough of 10-20 mg/L, depending on the location and the severity of the infection. The new guidelines move away from this traditional approach and instead recommend dosing vancomycin to achieve an area under the curve to minimum inhibitor concentration (AUC/MIC) ratio of ≥ 400. Bayesian software programs, rather than traditional PK calculations, are recommended to determine reliable estimates of daily AUC values. Although this can be done with trough-only sampling, the guidelines state that the accuracy of the AUC estimation is higher if both peak and trough vancomycin levels are available. This is a change, as previously monitoring vancomycin use for most infections only required trough sampling.

The guidelines cite the limited number of studies supporting the previously recommended trough range of 15-20 mg/L for serious infections and the emerging evidence that troughs may not be as well correlated to AUC values as once thought as reasons for the major change in vancomycin dosing targets. The new guidelines specifically recommend that the use of trough-only monitoring and targets should be avoided.

There are various Bayesian software programs available, but many have been developed by commercial entities and require a fee for use and access. Advantages of these include the ability to collect vancomycin in the first 24-48 hours of therapy rather than having to wait until steady-state was achieved, which has traditionally been viewed as after the third maintenance dose. If clinicians do not have access to a software program, the AUC can be calculated using 2 timed steady-state vancomycin levels and first-order PK equations. Both the Bayesian software program and the PK equation approaches require obtaining 2 vancomycin levels; the first should be obtained 1-2 hours after the infusion ends and the second as a trough. The frequency of monitoring is left to the discretion of the clinician, with at least once-weekly monitoring recommended for hemodynamically stable patients. More frequent or daily monitoring should be considered for patients who are hemodynamically unstable or those with end-stage kidney disease.

The guidelines also make new recommendations regarding vancomycin dosing, particularly before the AUC/MIC ratio is known. For patients with normal kidney function, doses of 15-20 mg/kg, based on actual body weight can be administered every 8-12 hours. For critically ill patients a loading dose of 20-35 mg/kg can be considered, but should not exceed 3,000 mg. However, it is important to remember that this dosing regimen may not achieve goal therapeutic targets if the MIC is above 1 mg/L. It is possible that some patients may not achieve targets based on this dosing for other reasons as well. In these patients, a 15-20 mg/king loading dose followed by a daily maintenance dose of 30-40 mg/kg (up to 60 mg/kg) administered via continuous infusion with a target steady-state vancomycin level of 20-25 mg/L may be considered.

One big concern some clinicians expressed with the previous target of a trough of 15-20 mg/L was the increased incidence of acute kidney injury (AKI). To minimize the risk of AKI, daily vancomycin AIC values (assuming a MIC of 1 mg/L) should be kept in the range of 400-600mg/h/L.

Dosing in patients on dialysis depends on the dialyzer permeability. All dialysis patients should receive a loading dose of 25 mg/kg. Those with low permeability dialysis require a maintenance dose of 7.5 mg/kg at the end of dialysis while those on high permeability dialysis should receive a maintenance dose of 10 mg/kg. The new guidelines also include pediatric dosing recommendations, whereas the previous guidelines were targeted towards adults. While the same AUC targets are recommended, doses of 60-80 mg/kg/day in divided doses every 6 hours are recommended for children aged 3 months to 12 years, and 60-70 mg/kg/day in divided doses every 6 to 8 hours for those aged 12 years and older. The empiric daily dose of vancomycin should not exceed 3600 mg in children with good kidney function and most children will not need more than 3000 mg per day.

The new guidelines represent a substantial shift in the approach to vancomycin dosing and monitoring over the past decade. These changes will not only impact pharmacists practicing in hospitals, but those practicing in other settings such as infusion-pharmacy. Because most pharmacists were not taught this new dosing approach in pharmacy school, it is essential that those who might be tasked with dosing and monitoring vancomycin in their practices should become familiar with the new methods. Pharmacists who do not routinely manage vancomycin should still be familiar with the new dosing recommendations and targets, particularly as outpatient antibiotic therapy is utilized more often.

Many other health care providers may not be as comfortable with dosing, monitoring, and adjusting vancomycin for appropriate efficacy and safety as pharmacists, and they and patients still routinely look to the pharmacist as a source of knowledge for medication related issues. Pharmacists can also serve as a source of education to other health care providers about the new guidelines’ recommendations, many of whom may not be aware that the recommendations surrounding vancomycin in serious MRSA infections has changed. It is an important role for our profession, and will ensure a more optimal use of one of the most utilized antibiotics in our country.

REFERENCE

Rybak MJ, Le J, Ldise TP et al. Therapeutic monitoring of vancomycin for serious methicillin-resistant Staphylococcus aureus infections: a revised consensus guideline and review by the American Society of Health-System Pharmacists, the Infectious Diseases Society of America, the Pediatric Infectious Diseases Society, and the Society of Infectious Diseases Pharmacists. Am J Health-Syst Pharm.2020. doi 10.1093/ajhp/zxaa036 [Epub ahead of print]