A newly revised consensus guideline has provided updated recommendations for clinicians treating serious methicillin-resistant Staphylococcus aureus (MRSA) to better achieve clinical efficacy and ensure patient safety. An executive summary of the revised guideline was published in Clinical Infectious Diseases.

Based on recent clinical data, a reevaluation of vancomycin dosing and monitoring recommendations was required. The new guideline recommends an area under the curve over 24 hours to minimum inhibitory concentration (AUC/MIC) ratio of 400–600 mg*hour/L, assuming a broth microdilution of MIC of 1 mg/L for patients being treated for serious MRSA. This updated guideline was developed 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.

Previous guidelines from 2009 recommend trough monitoring as a surrogate marker for the target AUC/MIC. However, new data suggests that trough monitoring is associated with higher nephrotoxicity, therefore a reevaluation of the dosing and monitoring recommendations for vancomycin was suggested.

According to the summary, “recent [pharmacokinetic/pharmacodynamic] and toxicodynamic studies have demonstrated a significant reduction in vancomycin exposure and nephrotoxicity rates without compromising outcomes when AUC/MIC monitoring has been employed vs traditional trough monitoring approaches.” When using AUC/MIC-guided empiric dosing, it is recommended that, “the MIC should be assumed to be 1 mg/L based on broth microdilution methods, extensive antibiotic susceptibility data, and the inaccuracies or variability of automated susceptibility testing (±1 log2 dilutions).”


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The authors also suggest, based on clinical efficacy and safety data, a target AUC between 400 and 600 mg*hour/L for MRSA invasive infections in adult and pediatric populations. These targets should be achieved within 24 to 48 hours of the onset of therapy. Loading doses based on actual body weight are suggested for critically ill patients requiring renal replacement therapy or receiving continuous infusion therapy.

The full guidelines include 25 primary recommendations for vancomycin dosing and therapeutic drug monitoring, as well as specific recommendations for patients with obesity on renal replacement therapy and, for the first time, guidelines for pediatric patients.

Investigators do caution that “almost all” data available regarding PK/PD and toxicodynamics was derived from patients being treated for serious MRSA infection, and the majority of the data is also derived from patients with complicated bloodstream infections. Therefore, caution needs to be applied when extrapolating this information to mild, noninvasive infections or other bacterial species. Finally, the authors note that while the new guidelines conclude that AUC-guided dosing and monitoring is the most accurate and safest way to dose vancomycin, these recommendations should not circumvent clinical judgement.

Disclosure: Several authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.

Reference

Rybak MJ, Le J, Lodise 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 [published online July 13, 2020]. Clin Infect Dis. doi:10.1093/cid/ciaa303