Vancomycin infusion guidelines

Vancomycin modes of administration: Oral vs Intravenous

When vancomycin is given orally as a capsule or liquid that can be swallowed, its use is limited to treating two specific gastrointestinal infections:

Diarrhea associated with Clostridium difficile
Enterocolitis due to Staphylococcus aureus (including MRSA)

Vancomycin is poorly absorbed when taken orally, so it cannot help with infections in other parts of the body.

Intravenous vancomycin is commonly used for the treatment of resistant gram positive organisms such as methicillin resistant Staphylococcus aureus (MRSA), methicillin-resistant Staphylococcus epidermidis (MRSE) and select infections caused by Enterococci. It is commonly used for the treatment of these severe infections :

Heart valve infections (endocarditis)
Bone infections (osteomyelitis)
Blood infections (bacteremia)
Certain types of pneumonia
Serious skin infections
Meningitis

Vancomycin infusion related reactions

A possible side effect that may occur if vancomycin is infused too rapidly includes an allergic reaction (anaphylactoid reaction) known as « red man syndrome ». This is the most common allergic reaction in younger patients (under age 40) who received intravenous vancomycin. Red man syndrome consists of an itchy, hot, red rash that affects the upper body, face, and neck. It may occasionally spread to the extremities. It’s characterized by swelling under the skin, weakness, dizziness, a rapid heartbeat, fever, chills, chest pain, or back pain.

Other adverse reactions that may occur with a rapid infusion of vancomycin include:

Hypotension (a sudden drop in blood pressure)
Wheezing
Shortness of breath
Itching (pruritus)
Hives
Inflammation of a vein (phlebitis)
Flushing of the upper body (« red neck syndrome »)
Chest pain or muscle spasm
Neck pain or muscle spasm

Infusion-related reactions are related to both the concentration of vancomycin and the rate of infusion. To minimize these adverse reactions, vancomycin should be diluted before it is administered as per the product insert, and infused slowly over a period of at least one hour, or at an infusion rate of 10mg/min or less.

In general, most reactions that occur due to rapid infusion will resolve within 20 minutes, but they can occasionally persist for several hours. Supportive care may be provided for red man syndrome, which is a histamine reaction.

Vancomycin non-infusion related reactions

AUC24 vancomycin Bayesian-based dosing: Increasing therapeutic target attainment with decreased TDM cost

Ototoxicity

Hearing loss (ototoxicity) is a side effect that may occur after receiving intravenous vancomycin. It is more common in patients who were exposed to high levels of vancomycin over long periods of time. It has been discovered mostly in patients who had pre-existing hearing problems, those who were given a higher vancomycin dose, or were using vancomycin with other medications that can also damage hearing (such as aminoglycoside antibiotics).

Acute Kidney Injury

Acute kidney injury (AKI) is another possible side effect of vancomycin infusion. Certain patients are at high risk of developing AKI, including those who are obese, have pre-existing kidney problems (renal impairment), and the critically ill. In patients receiving vancomycin, a greater risk of nephrotoxicity occurs when doses exceed 4 grams per day and trough levels are higher than 15mcg/mL and an AUC above 600 mg-h/L is present.

Vancomycin associated AKI can be measured in different ways, but a common definition of AKI is either:

An increase in serum creatinine of >0.5 mg/dL or a 50% increase from baseline in consecutive daily readings, or
A decrease in calculated creatinine clearance of 50% from baseline on two consecutive days in the absence of an alternative explanation.
Newer studies suggest that a more sensitive threshold of an increase in serum creatinine >0.3 mg/dL over a 48-hour period may be an indicator of AKI.

AKI can be potentiated in patients that are receiving other medications that also require the kidney for elimination. It is important to monitor kidney function in patients receiving vancomycin who are also receiving other medications that can damage the kidneys, such as antimicrobials (e.g. amphotericin B, aminoglycosides, polymyxins, or piperacillin/tazobactam), loop diuretics, or certain types of chemotherapy such as cisplatin.

Vancomycin dosing

Historically, vancomycin may be dosed on a milligram/kg basis or a standard dose (e.g. 1000mg) , adjusted for renal function. Monitoring of serum vancomycin trough levels has been used to predict efficacy. For mild to moderate infections, a trough level of 10-15mg/L is usually targeted. For more severe infections, the goal is to achieve a trough level of between 15-20mg/L.

Some vancomycin nomograms have been developed to help patients achieve the higher vancomycin trough concentrations of 15 to 20mg/L. These nomograms are charts where clinicians can use a patient’s creatinine clearance and actual body weight to determine an appropriate starting and/or maintenance dose. Unfortunately, few studies have evaluated the safety and efficacy of using such nomograms to guide vancomycin therapy. One report found that using a nomogram did not reduce the incidence of AKI and significantly fewer patients met target trough levels.

The new 2019 draft of the revised vancomycin therapeutic guidelines recommends a move away from monitoring vancomycin trough levels and towards a metric that measures total drug exposure in relation to the organism’s minimum inhibitory concentration. This is referred to as an AUC24:MIC (24-hour area under the curve (AUC) to minimum inhibitory concentration ratio). Dosing vancomycin using trough-only monitoring will no longer be recommended. The previously mentioned nomograms would not be helpful when these new guidelines become the standard of care.

Continuous drug infusion vs intermittent drug infusion

The 2019 draft of the revised vancomycin therapeutic guidelines has recommended that patients maintain a steady-state vancomycin concentration of 20-25 mg/L during the entire dosing period. Using a continuous infusion is a fast and convenient way to reach this target drug concentration. It makes monitoring serum levels faster and easier since dose adjustments can be made instantly by changing the rate of infusion. Simply multiply the steady-state concentration by 24 to determine the AUC24 (Area under the concentration curve over 24 hours).

The risk of kidney damage or nephrotoxicity seems to be equal or lower with continuous infusion (as opposed to intermittent infusion). The major disadvantage to continuous infusion in critically ill patients is that vancomycin is not compatible with many commonly co-administered drugs, so separate IV lines or catheters must be placed specifically for vancomycin.

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