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Vancomycin is produced by fermentation of Amycol atopsis orientalis (formerly Nocardi a orientalis). It has
been available for approximately 40 years, but its popularity has increased significantly with the emergence
of MRSA in the early 1980s. Chemically, vancomycin has a glycosy lated hexapeptide chain that is rich in
unusual amino acids, many of which contain aromatic rings cross-linked by aryl ether bonds into a rigid
molecular framework.
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Vancomycin is used for serious bacterial infections caused by microorganisms sensitive
to this drug when penicillins and cephalosporins are ineffective for diseases such as sepsis,
endocarditis, pneumonia, pulmonary abscess, osteomyelitis, meningitis, and enterocolitis,
or when penicillins and cephalosporins cannot be tolerated by patients. Vancomycin is the
drug of choice for infections caused by methicillin-resistant forms of S. aureus, S. epidermidus, and other coagulase-negative staphylococci, as well as for endocarditis, diphtherioid
infections, and for patients very sick with colitis caused by C. difficile. A synonym of this
drug is vancocin.
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ChEBI: A complex glycopeptide from Streptomyces orientalis. It inhibits a specific step in the synthesis of the peptidoglycan layer in the Gram-positive bacteria Staphylococcus aureus and Clostridium difficile.
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Only very recently, despite decades of intensive use, have some vancomycin-resistant bacteria emerged
(vancomycin-resistant enterococcus [VRE] and vancomycin-resistant Staphylococcus aureus) [VRSA]. It is
alleged that these resistant strains emerged as a consequence of the agricultural use of avoparcin, a
structurally related antibiotic that has not found use for human infections in the United States but was used
in Europe before its recent ban. The mechanism of resistance appears to be alteration of the target
D-alanyl-D-alanine units on the peptidoglycan cell wall precursors to D-alanyl-D-lactate. This results in
lowered affinity for vancomycin due to lack of a key hydrogen bonding interaction. It is greatly feared that
this form of resistance will become common in the bacteria for which vancomycin is presently the last sure
hope for successful chemotherapy. If so, such infection
would become untreatable. These resistant strains are not yet common in clinically relevant strains, but most
authorities believe that this is only a question of time. Vancomycin-intermediate S.aureus, also called
glycoprotein-intermediate S.aureus (VISA), also has been reported. It appears to be resistant because of a
thickened peptidoglycan layer.
Mechanism of action
Vancomycin is a bacterial cell wall biosynthesis inhibitor. Evidence suggests that the active species is a
homodimer of two vancomycin units. The binding site for its target is a peptide-lined cleft having high affinity
for acetyl-D-alanyl-D-alanine and related peptides through five hydrogen bonds. It inhibits both
transglycosylases (inhibiting the linking between muramic acid and acetyl glucosamine units) and
transpeptidase (inhibiting peptide cross-linking) activities in cell wall biosynthesis. Thus,
vancomycin functions like a peptide receptor and interrupts bacterial cell wall biosynthesis at the same step
as the β-lactams do, but by a different mechanism. By covering the substrate for cell wall transamidase, it
prevents cross-linking resulting in osmotically defective cell walls.
Clinical Use
Although a number of adverse effects can result from IV infusion, vancomycin has negligible oral
activity. It can be used orally for action in the GI tract, especially in cases of Cl ostri di um difficile overgrowth. The useful spectrum is restricted to Gram-positive pathogens, with particular utility against
multiply-resistant, coagulase-negative staphylococci and MRSA, which causes septicemias, endocarditis,
skin and soft-tissue infections, and infections associated with venous catheters.
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Vancomycin is highly associated with adverse infusion-related events. These are especially prevalent with
higher doses and a rapid infusion rate. A rapid infusion rate has been shown to cause anaphylactoid
reactions, including hypotension, wheezing, dyspnea, urticaria, and pruritus. A significant drug rash (the
so-called red man syndrome) also can occur. These events are much less frequent with a slower infusion
rate.
In addition to the danger of infusion-related events, higher doses of vancomycin can cause nephrotoxicity
and auditory nerve damage. The risk of these effects is increased with elevated, prolonged concentrations,
so vancomycin use should be monitored, especially in patients with decreased renal function. The ototoxicity
may be transient or permanent and more commonly occurs in patients receiving high doses, patients with
underlying hearing loss, and patients being treated concomitantly with other ototoxic agents (i.e.,
aminoglycosides).
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