Vancomycin is a medication of last resort that is used to treat infections with antibiotic-resistant bacteria, such as methicillin-resistant Staphylococcus aureus (MRSA). MRSA is frequently responsible for difficult-to-treat skin and soft-tissue infections. It may also be a causative agent in more invasive infections, including pneumonia, bacteremia, osteomyelitis, endocarditis, or meningitis. Vancomycin is usually considered the drug of choice to treat MRSA in the inpatient setting. However, it must be dosed appropriately to be effective and to prevent the emergence of resistance. Dose individualization is critical.
Unlike beta-lactam antibiotics (such as penicillin), which are dependent on the length of time above the minimum inhibitory concentration (MIC), vancomycin is dependent on the area under the curve:MIC ratio. This means that vancomycin concentrations need to exceed by four to five times the MRSA MIC at the site of infection to be effective and prevent resistance. Clinically, this translates into maintaining vancomycin trough concentrations between 10 and 20 µg/mL for skin and soft-tissue infections and between 15 and 20 µg/mL for infections in areas that are difficult for vancomycin to penetrate, including the lung, bone, CSF, and undrained abscesses. Underdosing has resulted in therapy failure and can lead to the emergence of heteroresistant vancomycin intermediate Staphylococcus aureus (hVISA).1 If vancomycin is not properly dosed within the first 36 hours, genes can be activated within MRSA that induce vancomycin resistance. Therefore, vancomycin should be dosed early and aggressively, with a loading dose given for rapid achievement of target concentrations.
Historically, providers have been afraid to aggressively use vancomycin secondary to potential toxicities, such as ototoxicity and nephrotoxicity. A retrospective review of the literature over the past 35 years has shown that these "toxicities" were actually associated with initial vancomycin impurities.2,3 Because vancomycin has been adequately purified, such toxicities have been essentially eliminated; those that have been reported involved the use of concomitant medications or other health conditions that predisposed patients to ototoxicity or nephrotoxicity. Commonly used diuretics (such as furosemide) are more closely associated with those toxicities than vancomycin. There is a much greater risk to the patient from underdosing vancomycin than by being aggressive.
Adult patients with normal renal function should receive a vancomycin loading dose of 20 mg/kg IV, followed by 15 mg/kg IV every 12 hours. For life-threatening or invasive MRSA infections in the bone, lung, bloodstream, or CSF, a loading dose of 25 mg/kg IV and maintenance doses of 20 mg/kg IV are acceptable.4 Trough concentrations should be measured prior to the fourth dose. There is little rationale for monitoring peak vancomycin concentrations, and they are generally avoided. While there are different approaches to vancomycin dosing in patients with kidney disease, an initial loading dose is acceptable.
The take-home message is that vancomycin resistance is emerging, and not all MRSA strains continue to be susceptible to vancomycin. To help prevent resistance and effectively treat infection, take the following steps:
1. Identify the site of infection, and determine the goal trough. Troughs should be between 10 and 20 µg/mL and kept at the higher range (between 15 and 20 µg/mL) for life-threatening infections or sites where vancomycin penetration is difficult.
2. Give a loading dose of 20 mg/kg for most infections and 25 mg/kg for life-threatening infections.
3. Dose appropriately. Give 15 mg/kg
for most infections and 20 mg/kg for life-threatening infections. For patients with normal renal function, the dosing interval is usually every 12 hours. Young, otherwise healthy patients may require dosing every 8 hours. The dosing interval is variable for patients with kidney disease and may range from every 24 to every 72 hours. Consult the pharmacy for dosing, especially in patients with unusual pharmacokinetics (burns, cystic fibrosis, obesity, kidney disease).
4. Measure the trough concentration 30 minutes prior to the fourth dose.
5. Adjust the dose, if needed, based on the trough. A kinetics calculator can be very helpful.
On a final note, remember to discontinue vancomycin for methicillin-sensitive Staphylococcus aureus (MSSA). Antistaphylococcal penicillins are the drugs of choice for MSSA. The antistaphylococcal penicillins are easy to remember by the acronym CONDM (cloxacillin, oxacillin, nafcillin, dicloxacillin, methicillin). JAAPA
Elizabeth duPreez, PharmD, works at Flagstaff Medical Center, Flagstaff, Arizona. She completed her Doctor of Pharmacy at the University of Arizona, Tucson, and has an extensive background in microbiological research.
REFERENCES
1. Jones RN. Microbiological features of vancomycin in the 21st century: minimum inhibitory concentration creep,
bactericidal/static activity, and applied breakpoints to predict clinical outcomes or detect resistant strains. Clin Infect Dis. 2006;42(suppl 1):S13-S24.
2. Darko W, Medicis JJ, Smith A, et al. Mississippi mud no more: cost-effectiveness of pharmacokinetic dosage adjustment of vancomycin to prevent nephrotoxicity. Pharmacotherapy. 2003;23(5):643-650.
3. Cantú TG, Yamanaka-Yuen NA, Lietman PS. Serum vancomycin concentrations: reappraisal of their clinical value. Clin Infect Dis. 1994;18(4):533-543.
4. Hidayat LK, Hsu DI, Quist R, et al. High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity. Arch Intern Med. 2006;
166:2138-2144.