Vancomycin belongs to a class of antibiotics called glycopeptides. Drugs in this class are composed of a cyclic peptide bound by two sugar molecules (glycogen), hence the class name glycopeptide!
Vancomycin’s stem “-mycin” is derived from Streptomyces bacteria, reminding us that vancomycin mainly covers gram-positive organisms.
Additional antibiotics in the glycopeptide class include:
- Dalbavancin
- Telavancin
- Oritavancin
The newer antibiotics in this class all end in –vancin as in similar to vancomycin.
Mechanism of Action
Gram-positive bacterial cell walls are made of a peptidoglycan matrix that gives them structure and rigidity. This is done via transpeptidase-mediated cross-linking as shown in the figure below.
Side Note – transpeptidase is a type of bacterial enzyme or molecule that cross-links peptidoglycan chains making the cell wall stable and rigid.
Vancomycin binds to D-alanyl-D-alanine (also known as D-ala-D-ala) terminus portion of the peptide precursor on the outer surface of cell membranes preventing transpeptidase-mediated cross-linking. Preventing peptidoglycan cross-linking interferes with cell wall synthesis resulting in weak bacterial cell walls and ultimately cell death.
Another way to look at it!
The cell walls are like LEGO pieces linking together. The more that are linked, the stronger the structure or cell wall becomes. Vancomycin prevents cross-linking by attaching to the nubs of the LEGO pieces (D-ala-D-ala), therefore preventing cross-linking. Check out the beautiful illustration below to get a better understanding.
Ultimately, this leads to an unstable structure and the LEGO pieces break apart leading to bacteria death. This is how vancomycin exhibits bactericidal killing versus bacteriostatic.
- Bactericidal: killing the bacteria
- Bacteriostatic: prevents the bacteria from replicating
MNEMONIC:
Bactericidal drugs cause bacteria to be suicidal and die while
bacteriostatic drugs cause bacteria to be static and unmoving
Vancomycin Coverage
Mainly gram-positive cocci
- Staphylococcus aureus (including MSSA and MRSA)
- Staphylococcus epidermidis (including MSSE and MRSE)
- Streptococcus spp.
- Enterococcus spp.
- Clostridioides difficile
Interesting fact
Gram-negatives do NOT have a thick cell wall and lack the D-ala-D-ala sequence, making vancomycin useless against them
Vancomycin Side Effects
Like most drugs administered intravenously, vancomycin can cause infusion-related reactions causing hypotension, redness, and itching. Other common side-effects of vancomycin include:
- Nephrotoxicity
- Ototoxicity
- Thrombophlebitis
- Vancomycin infusion reaction (VIR) – previously known as “red man syndrome”
A mnemonic to remember these side-effects would be that vancomycin can cause a TON of Vancomycin infusion reactions
Thrombophlebitis
Ototoxicity (rare)
Nephrotoxicity
Vancomycin infusion reactions
Vancomycin Pharmacokinetics
ABSORPTION:
Oral vancomycin has a bioavailability of <10% and is therefore poorly absorbed from the gastrointestinal tract. It should only be given intravenously when treating systemic infections.
EXCEPTION: Vancomycin is given orally in Clostridium difficile-associated colitis as high concentrations are achieved in the colon. Trough levels are not needed as it is not absorbed from the GI tract into the bloodstream.
METABOLISM:
Vancomycin is mainly given via injection directly into the bloodstream. Therefore, vancomycin undergoes no metabolism and is excreted unchanged in the urine.
DISTRIBUTION:
Vancomycin has a large volume of distribution, Vd = 0.7 L/kg, distributing well into tissues and intracellular fluids. The only exception is cerebrospinal fluid (CSF), where vancomycin has poor penetration. This changes when the meninges are inflamed, leading to better penetration of vancomycin during meningitis. (How convenient 😎)
Since vancomycin distributes well into most tissues, total/actual body weight is recommended for calculations versus ideal or adjusted body weight. At some institutions, morbidly obese patients are dosed based on adjusted body weight while others dose on total body weight and cap their dose at 2,500 mg. It is important to follow your institution’s policy as it relates to morbidly obese patients.
*2020 Guideline Update*
ASHP updated their recommendations in obesity, encouraging the use of actual body weight for vancomycin dosing and capping the dose at 3,000 mg for loading doses and 4,500 mg/day for empiric maintenance doses.
ELIMINATION:
- IV vancomycin is primarily eliminated by the kidneys
- Oral vancomycin is primarily eliminated in the feces
Vancomycin exhibits first-order elimination where a constant proportion or percentage of the drug is eliminated over a period of time versus a constant amount. (🧠 Remember the mnemonic from our last lesson: you have to FIRST cut the pie into PORTIONS)
Vancomycin Therapeutic Goals
Vancomycin requires routine drug monitoring to ensure effectiveness and prevent adverse effects. Trough levels are drawn to measure therapeutic outcomes because vancomycin follows time-dependent killing. These levels are drawn 30 minutes prior to the administration of the next dose to ensure that drug concentrations are maintained above the minimum inhibitory concentration (MIC).
Trough goals based on indication (KNOW THIS):
- 10-15 mcg/mL: urinary tract infections (UTI), cellulitis
- 15-20 mcg/mL: bacteremia, pneumonia
Interesting fact
Back in the days, goal troughs used to be lower (5-10 mcg/mL) for serious infections. However, since resistance rates have increased, higher goal troughs are needed to adequately treat the infection
*2020 Guideline Update Alert*
ASHP released new consensus guidelines recommending changes in vancomycin monitoring that emphasized a AUC/MIC ratio of 400-600 (assuming a MIC of 1 mg/L) over targeting a goal trough of 10-20 mcg/mL. Bayesian software programs, compared to traditional PK calculations, are recommended to evaluate daily AUC values and trough-only monitoring is not recommended. If Bayesian software is not available, AUC can also be manually calculated using first-order PK equations using two levels (peak and a trough). This change in practice will require further education to pharmacists and nurses to ensure success.
That’s it! You have finished the second lesson. Do you think you have mastered the understanding of vancomycin? We will just have to put your knowledge to the test.
You will be asked a series of questions. If you pass, you will gain access to unlock the next lesson and be one step closer to escaping the lab.