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Appropriate vancomycin dosing requires consideration of the infection site, patient weight, renal function, and pathogen susceptibility
Vancomycin is restricted to parenteral administration for the treatment of systemic infections. It is distributed widely to various tissues and body fluids, with a volume of distribution ranging from 0.4 to 1.0 L/kg. Penetration of vancomycin may vary by site and concomitant disease states.
In vitro and animal model studies describing vancomycin pharmacodynamics indicate the rate of killing depends primarily upon time of concentration exceeding the organism's minimum inhibitory concentration (MIC). The area under the time concentration curve (AUC; AUC:MIC ratio) is the best predictor of efficacy.
Adverse effects of vancomycin potentially related to dosing and/or rate of administration include infusion-related reactions, nephrotoxicity, and ototoxicity. Risks of nephrotoxicity may be increased with the concomitant use of nephrotoxins (such as aminoglycosides) and/or piperacillin-tazobactam.
Comparison of the incidence of vancomycin-induced nephrotoxicity in hospitalized patients with and without concomitant piperacillin-tazobactam. - PubMed - NCBI
Comparison of acute kidney injury during treatment with vancomycin in combination with piperacillin-tazobactam or cefepime. - PubMed - NCBI
Vancomycin-associated nephrotoxicity in adult medicine patients: incidence, outcomes, and risk factors. - PubMed - NCBI
Department of Pharmacy Practice,
Albany College of Pharmacy
Relationship between initial vancomycin concentration-time profile and nephrotoxicity among hospitalized patients. - PubMed - NCBI
Larger vancomycin doses (at least four grams per day) are associated with an increased incidence of nephrotoxicity. - PubMed - NCBI
Initial maintenance vancomycin dosing of 15 to 20 mg/kg should be administered to patients with normal renal function, impaired renal function, and/or obesity. For rapid achievement of target concentrations in seriously ill patients, a loading dose of 25 to 30 mg/kg may be administered. Maintenance dosing and dosing frequency should be determined based on weight and creatinine clearance
Vancomycin trough concentrations of at least 10 mcg/mL should be achieved. In the setting of invasive infections (such as endocarditis, osteomyelitis, prosthetic joint infections, and infections involving the central nervous system), many favor vancomycin trough concentrations of 15 to 20 mcg/mL.
Serum trough concentration monitoring should be performed in patients receiving vancomycin therapy longer than three days. Once target concentrations are achieved, the trough vancomycin concentration should be monitored at least weekly for patients in the circumstances outlined above.
For patients on hemodialysis, a single initial dose of 15 to 20 mg/kg should be administered following hemodialysis. For patients undergoing hemodialysis via the newer, more permeable high-flux membranes, repeat vancomycin dosing is often required following each session as described above.
We suggest initial antibiotic management of methicillin-resistant Staphylococcus aureus (MRSA) bacteremia with intravenous vancomycin or daptomycin (Grade 2C).
Persistent bacteremia may be due to a collection, the presence of a prosthetic device, or an endovascular source of infection that requires surgery. However, if antibiotic failure seems the most likely explanation and if the minimum inhibitory concentration (MIC) approaches the limit of the susceptible range (ie, 2 mcg/mL), vancomycin should be discontinued and therapy switched to an alternative agent.
If an alternative agent for treatment of MRSA bacteremia is needed due to vancomycin intolerance or inadequate response to treatment, we suggest treating with daptomycin or linezolid (Grade 2C). Susceptibility testing should be performed; in general, we favor daptomycin over linezolid.
We recommend initial antibiotic management of MRSA osteomyelitis with intravenous vancomycin or daptomycin (Grade 1C).