Actions of Vancomycin in details
The bactericidal action of Vancomycin results primarily from inhibition of cell-wall biosynthesis. Specifically, Vancomycin prevents incorporation of N-acetylmuramic acid (NAM)- and N-acetylglucosamine (NAG)-peptide subunits from being incorporated into the peptidoglycan matrix; which forms the major structural component of Gram-positive cell walls. The large hydrophilic molecule is able to form hydrogen bond interactions with the terminal D-alanyl-D-alanine moieties of the NAM/NAG-peptides. Normally this is a five-point interaction. This binding of Vancomycin to the D-Ala-D-Ala prevents the incorporation of the NAM/NAG-peptide subunits into the peptidoglycan matrix. In addition, Vancomycin alters bacterial-cell-membrane permeability and RNA synthesis. There is no cross-resistance between Vancomycin and other antibiotics. Vancomycin is not active in vitro against gram-negative bacilli, mycobacteria, or fungi.
How should I take Vancomycin?
Some medicines given by injection may sometimes be given at home to patients who do not need to be in the hospital for the full time of treatment. If you are receiving Vancomycin at home, make sure you clearly understand and carefully follow your doctor's instructions.
To help clear up your infection completely, Vancomycin must be given for the full time of treatment, even if you begin to feel better after a few days. Also, Vancomycin works best when there is a constant amount in the blood. To help keep the amount constant, Vancomycin must be given on a regular schedule.
Dosing
The dose of Vancomycin will be different for different patients. Follow your doctor's orders or the directions on the label. The following information includes only the average doses of Vancomycin. If your dose is different, do not change it unless your doctor tells you to do so.
The amount of medicine that you take depends on the strength of the medicine. Also, the number of doses you take each day, the time allowed between doses, and the length of time you take the medicine depend on the medical problem for which you are using the medicine.
- For injection dosage form:
- For treatment of bacterial infections:
- Adults and teenagers—7.5 milligrams (mg) per kilogram (kg) of body weight, or 500 mg, injected into a vein every six hours; or 15 mg per kg of body weight, or 1 gram, injected into a vein every twelve hours.
- Children 1 month to 12 years of age—10 milligrams (mg) per kilogram (kg) of body weight injected into a vein every six hours; or 20 mg per kg of body weight injected into a vein every twelve hours.
- Infants 1 week to 1 month of age—15 milligrams (mg) per kilogram (kg) of body weight injected into a vein at first, then 10 mg per kg of body weight injected into a vein every eight hours.
- Newborns younger than 1 week of age—15 milligrams (mg) per kilogram (kg) of body weight injected into a vein at first, then 10 mg per kg of body weight injected into a vein every twelve hours.
- For treatment of bacterial infections:
Vancomycin administration
Intravenous: Administer Vancomycin with a final concentration not to exceed 5 mg/mL by IV intermittent infusion over at least 60 minutes (recommended infusion period of ≥30 minutes for every 500 mg administered [ASHP/IDSA/SIDP {Rybak 2009}]); in adult patients in need of fluid restriction, a concentration up to 10 mg/mL may be used, but risk of infusion-related reactions is increased. Not for IM administration.
If a maculopapular rash appears on the face, neck, trunk, and/or upper extremities (red man syndrome), slow the infusion rate to over 1/ to 2 hours and increase the dilution volume (Healy 1990; Rybak 1986; Szymusiak-Mutnick 1996). Hypotension, shock, and cardiac arrest (rare) have also been reported with too rapid of infusion. Administration of antihistamines prior to infusion may prevent or minimize this reaction (Rybak 1986; Wilhem 1999).
Irritant; ensure proper needle or catheter placement prior to and during infusion. Avoid extravasation.
Extravasation management: If extravasation occurs, stop infusion immediately and disconnect (leave cannula/needle in place); gently aspirate extravasated solution (do NOT flush the line); remove needle/cannula; elevate extremity. Information conflicts regarding the use of dry cold or dry warm compresses (Hurst 2004; Reynolds 2014); however, dry warm compresses may be of benefit in increasing local blood flow to enhance drug removal from the extravasation site. Intradermal hyaluronidase may be considered for refractory cases (Reynolds 2014).
Hyaluronidase: Intradermal: Inject a total of 1 mL (15 units/mL) as 5 separate 0.2 mL injections (using a tuberculin syringe) along injection site and edematous area (Reynolds 2014).
Antibiotic lock technique (off-label use): Instill prepared Vancomycin lock solution into each lumen of the catheter access port using a volume sufficient to fill the catheter (2 to 5 mL) with a dwell time of 48 to 72 hours (dependent on frequency of catheter use). Withdraw lock solution prior to catheter use; replace with fresh Vancomycin lock solution after catheter use (IDSA [Mermel 2009]; LaPlante 2007).
Intraventricular (off-label route): Use preservative-free preparations only. May be administered intraventricularly with a final concentration of 2.5 to 10 mg/mL for the treatment of CSF shunt infections. When administered through a ventricular drain, clamp drain for 15 to 60 minutes before opening the drain to allow Vancomycin solution to equilibrate in the CSF (IDSA [Tunkel 2004; Tunkel 2017]; Ng 2014).
Intravitreal (off-label route): May administer Vancomycin intravitreally with a final concentration of 1 mg/0.1 mL NS or sterile water (Durand 2019; Kelsey 1995).
Oral:
Solution (Firvanq): Shake reconstituted oral solution well before each use.
Injection: Reconstituted powder for injection (not premixed solution) may be diluted and used for oral administration; common flavoring syrups may be added to improve taste. The unflavored, diluted solution may also be administered via nasogastric tube.
Rectal (off-label route): May be administered as a retention enema per rectum (IDSA/SHEA [McDonald 2018]); 500 mg in 100 to 500 mL of NS, volume may depend on length of segment being treated. If sodium chloride causes hyperchloremia could use solution with lower chloride concentration (eg, LR) (ACG [Surawicz 2013]).
Vancomycin pharmacology
Mechanism of Action
Vancomycin is an antibacterial drug.
Pharmacokinetics
Vancomycin is poorly absorbed after oral administration. During multiple dosing of 250 mg every 8 hours for 7 doses, fecal concentrations of Vancomycin in volunteers exceeded 100 mg/kg in the majority of samples. No blood concentrations were detected and urinary recovery did not exceed 0.76%. In anephric subjects with no inflammatory bowel disease who received Vancomycin oral solution 2 g for 16 days, blood concentrations of Vancomycin were less than or equal to 0.66 μg/mL in 2 of 5 subjects. No measurable blood concentrations were attained in the other 3 subjects. Following doses of 2 g daily, concentrations of drug were >3100 mg/kg in the feces and <1 μg/mL in the serum of subjects with normal renal function who had C. difficile-associated diarrhea. After multiple-dose oral administration of Vancomycin, measurable serum concentrations may occur in patients with active C. difficile-associated diarrhea, and, in the presence of renal impairment, the possibility of accumulation exists. It should be noted that the total systemic and renal clearances of Vancomycin are reduced in the elderly.
Microbiology
Mechanism of Action
The bactericidal action of Vancomycin against Staphylococcus aureus and the vegetative cells of Clostridium difficile results primarily from inhibition of cell-wall biosynthesis.
In addition, Vancomycin alters bacterial-cell-membrane permeability and RNA synthesis.
Mechanism of resistance
Staphylococcus aureus:
S. aureus isolates with Vancomycin minimal inhibitory concentrations (MICs) as high as 1024 mcg/mL have been reported.
The exact mechanism of this resistance is not clear but is believed to be due to cell wall thickening and potentially the transfer of genetic material.
Clostridium difficile: Isolates of C. difficile generally have Vancomycin MICs of <1 mcg/mL, however Vancomycin MICs ranging from 4 mcg/mL to 16 mcg/mL have been reported. The mechanism which mediates C. difficile's decreased susceptibility to Vancomycin has not been fully elucidated.
Vancomycin has been shown to be active against susceptible isolates of the following bacteria in clinical infections as described in the INDICATIONS AND USAGE section.
Gram-positive bacteria
Staphylococcus aureus (including methicillin-resistant isolates) associated with enterocolitis
Anaerobic Gram-positive bacteria
Clostridium difficile isolates associated with C. difficile associated diarrhea.
References
- NCIt. "Vancomycin: NCI Thesaurus (NCIt) provides reference terminology for many systems. It covers vocabulary for clinical care, translational and basic research, and public information and administrative activities.". https://ncit.nci.nih.gov/ncitbrowser... (accessed September 17, 2018).
Reviews
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Information checked by Dr. Sachin Kumar, MD Pharmacology
