Vancomycin Level

Vancomycin is an antibiotic drug used to treat serious, life-threatening infections by gram-positive bacteria that are resistant to less-toxic agents.

The reference range for vancomycin trough levels is 5-15 mcg/mL. The reference range for vancomycin peak levels is 20-40 mcg/mL. ^[1]

Vancomycin trough concentrations below 10 µg/mL are associated with inadequate therapy and an increased risk of developing bacterial resistance.

Vancomycin trough concentrations above the therapeutic range may increase the risk of nephrotoxicity.

Vancomycin peak concentrations above the therapeutic range may be associated with an increased the risk of nephrotoxicity, although peak concentrations do not correlate well with toxicity.

Specifics for collection and panels are as follows:

• Specimen type: Blood serum

• Container: Vacutainer, red top

• Collection method: Venipuncture

• Specimen volume: 1 mL

Other instructions are as follows:

• Do not draw specimens until steady state is achieved (ie, before fourth dose)

• Draw trough specimen immediately before (≤30 min) next dose

• Draw peak specimen 1-2 hours after completion of intravenous dosage

Related tests: Blood urea nitrogen (BUN), serum creatinine, creatinine clearance, Clostridium difficile toxin

Description

Vancomycin is a glycopeptide antibiotic first isolated in 1953. It is a natural occurring antimicrobial synthesized by soil bacterium Amycolatopsis orientalis. Generic vancomycin is became available and approved for use in 1958 and quickly became a common antibiotic in treating rapidly growing penicillin-resistant Staphylococcus species. However, this antibiotic never became a first-line treatment owing to its poor oral bioavailability and its various adverse effects leading, to the belief that less toxic alternatives may be more beneficial. ^[2]

The emergence of pseudomembranous enterocolitis, coupled with the spread of methicillin-resistant Staphylococcus aureus (MRSA), led to a resurgence in the use of vancomycin. It is used to treat serious, life-threatening infections by gram-positive bacteria that are resistant to less-toxic agents. The oral formulation, which is not absorbed, is used in the treatment of pseudomembranous colitis caused by C difficile. ^[3] Vancomycin is also used in patients who are intolerant or allergic to beta-lactams.

Indications/Applications

Common uses of vancomycin in current medical practice include the following:

• MRSA infection

• Multidrug-resistant Staphylococcus epidermidis (MRSE) infection

• In individuals with severe allergies to penicillin

• Pseudomembranous colitis (C difficile infection)

• Prophylaxis for endocarditis

• Surgical prophylaxis for implantation of prostheses in individuals at high risk or institutions with high rates of MRSA or MRSE infection

General indications for measuring vancomycin trough levels include risk of nephrotoxicity and inadequate therapeutic response. Monitor at regular intervals. Specifically, trough levels should be measured in the following patients at risk for nephrotoxicity:

• Patients also receiving other potentially nephrotoxic drugs - Angiotensin-converting enzyme inhibitors (ACE inhibitors), angiotensin receptor blockers (ARBs), NSAIDs, aminoglycoside antibiotics, sulfonamides, chemotherapy agents

• Patients with reduced or changing renal function

• Patients receiving higher than usual doses

• Patients on prolonged therapy (>3-5 days)

Vancomycin dosing adjustments based on creatinine clearance (CrCl) for patients with renal impairment are as follows ^[4] :

• CrCl greater than 60 mL/min: No adjustment required

• CrCl 40-60 mL/min: 10-15 mg/kg q12-24h

• CrCl 20-40 mL/min: 5-10 mg/kg q24h

• CrCl 10-20 mL/min: 5-10 mg/kg q24-48h

• CrCl less than 10 mL/min: 10-15 mg/kg IV loading + redose according to serum vancomycin level

• Dialysis: 15-20 mg/kg load, then 500 mg IV post hemodialysis only

Vancomycin Monitoring

The application of serum vancomycin monitoring has been a source of debate for many years. A consensus statement from the American Society of Health-System Pharmacists, the Infectious Diseases Society of America (IDSA), and the Society of Infectious Diseases Pharmacists ^[5] contains recommendations for monitoring vancomycin therapy, based on a critical evaluation of the available scientific evidence. ^[6] Their recommendations are as follows:

• Vancomycin serum concentrations should be checked to optimize therapy and used as a surrogate marker of effectiveness.

• Trough, rather than peak, levels should be monitored.

• Trough levels should be checked just before the fourth dose, when steady-state levels are likely to have been achieved. More frequent monitoring may be considered in patients with fluctuating renal function.

• Trough levels should be higher than 10 mg/L to prevent the development of resistance.

• To improve antibiotic penetration and optimize the likelihood of achieving pharmacokinetic and pharmacodynamic targets, trough levels of 15 to 20 mg/L are recommended for pathogens with a vancomycin minimum inhibitory concentration (MIC) of 1 mg/L or higher and for complicated infections such as endocarditis, osteomyelitis, meningitis, and hospital-acquired pneumonia.

• For prolonged courses, it is appropriate to check vancomycin levels weekly in hemodynamically stable patients and more often in those who are not hemodynamically stable.

Toxicity/Adverse Effects

A retrospective analysis of patients receiving vancomycin between 1974 and 1981 revealed the following findings ^[7] :

• Auditory toxicity was not seen.

• Fever and rash were uncommon (1-3% of patients).

• Phlebitis affected 13% of patients and necessitated discontinuation of therapy for 2% of patients.

• Nephrotoxicity was infrequent (5% of patients) and reversible, but it was possibly potentiated by concomitant aminoglycoside therapy.

• Neutropenia occurred in 2% of patients but was rapidly reversible.

In rare cases, interstitial nephritis arises in association with vancomycin. ^{[8, 2]} Reportedly, the combination of vancomycin and aminoglycosides can result in renal failure, particularly in adults who are undergoing prolonged therapy and have trough serum vancomycin concentrations of 10 mg/L or more. ^{[9, 10]}

A meta-analysis demonstrates that therapeutic drug monitoring significantly increases the rate of clinical efficacy and decreases the rate of nephrotoxicity in patients treated with vancomycin. ^[11]

Considerations

Evaluate BUN, creatinine, and CrCl before starting therapy and at intervals, or as needed to monitor renal status thereafter.

Each hospital may have different protocols with antibiotic stewardship, vancomycin level monitoring, and treatment duration. Please consult local hospital infectious diseases team/local hospital network protocol.