Glycopeptide antibiotic
Encyclopedia
Glycopeptide antibiotics are a class of antibiotic
drugs
. The class is composed of glycosylated
cyclic or polycyclic nonribosomal peptide
s. Significant glycopeptide antibiotics include vancomycin
, teicoplanin
, telavancin
, bleomycin
, ramoplanin
, and decaplanin.
synthesis. They bind to the amino acids within the cell wall preventing the addition of new units to the peptidoglycan. In particular, they bind to acyl-D-alanyl-D-alanine in peptidoglycan.
. Effective against principally gram-positive cocci, they exhibit a narrow spectrum of action, and, while they are bacteriostatic against most species, they are bacteriocidal only against the enterococci. Some tissues are not penetrated very well by glycopeptides, and they do not penetrate into the CSF
.
for cases of Methicillin-resistant Staphylococcus aureus, however several newer classes of antibiotics, including linezolid
of the oxazolidinone class, and daptomycin
of the lipopeptide class have proven to have activity against MRSA. Vancomycin-resistant staphylococcus aureus has been seen in some countries.
While not approved for use in the U.S., teicoplanin was discovered in the early 1990s and is marketed in Europe. It is more lipophillic than vancomycin, as it has more fatty acid chains. It is considered to be 50 to 100 times more lipophillic than vancomycin. Teicoplanin has an increased half-life compared to vancomycin, as well as having better tissue penetration. It can be two to four times more active than vancomycin, but it does depend upon the organism. Teicoplanin is more acidic, forming water-soluble salts, so it can be given intramuscularly. Teicoplanin is much better at penetrating into leucocytes and phagocytes than vancomycin.
and dalbavancin
. Possessing longer half-lives than vancomycin, these newer candidates may demonstrate improvements over vancomycin due to less frequent dosing and activity against vancomycin-resistant bacteria.
and phlebitis
at the injection site if given too rapidly. Pain at site of injection is indeed a common adverse event. One of the side-effects is Red man syndrome, an idiosyncratic reaction to bolus, caused by histamine release. Some other side-effects of vancomycin are nephrotoxicity including renal failure and interstitial nephritis, blood disorders including neutropenia, and deafness, which is reversible once therapy has stopped. Oral preparations are available, however they are not absorbed from the lumen of the gut, so are of no use in treating systemic infections. The oral preparations are formulated for the treatment of infections within the Gastro-Intestinal tract, Clostridium difficile
, for example. Over 90% of the dose is excreted in the urine, therefore there is a risk of accumulation in patients with renal impairment, so therapeutic drug monitoring (TDM) is recommended.
Antibiotic
An antibacterial is a compound or substance that kills or slows down the growth of bacteria.The term is often used synonymously with the term antibiotic; today, however, with increased knowledge of the causative agents of various infectious diseases, antibiotic has come to denote a broader range of...
drugs
Medication
A pharmaceutical drug, also referred to as medicine, medication or medicament, can be loosely defined as any chemical substance intended for use in the medical diagnosis, cure, treatment, or prevention of disease.- Classification :...
. The class is composed of glycosylated
Glycosylation
Glycosylation is the reaction in which a carbohydrate, i.e. a glycosyl donor, is attached to a hydroxyl or other functional group of another molecule . In biology glycosylation refers to the enzymatic process that attaches glycans to proteins, lipids, or other organic molecules...
cyclic or polycyclic nonribosomal peptide
Nonribosomal peptide
Nonribosomal peptides are a class of peptide secondary metabolites, usually produced by microorganisms like bacteria and fungi. Nonribosomal peptides are also found in higher organisms, such as nudibranchs, but are thought to be made by bacteria inside these organisms...
s. Significant glycopeptide antibiotics include vancomycin
Vancomycin
Vancomycin INN is a glycopeptide antibiotic used in the prophylaxis and treatment of infections caused by Gram-positive bacteria. It has traditionally been reserved as a drug of "last resort", used only after treatment with other antibiotics had failed, although the emergence of...
, teicoplanin
Teicoplanin
Teicoplanin is an antibiotic used in the prophylaxis and treatment of serious infections caused by Gram-positive bacteria, including methicillin-resistant Staphylococcus aureus and Enterococcus faecalis. It is a glycopeptide antibiotic extracted from Actinoplanes teichomyceticus, with a similar...
, telavancin
Telavancin
Telavancin is a bactericidal lipoglycopeptide for use in MRSA or other Gram-positive infections. Telavancin is a synthetic derivative of vancomycin....
, bleomycin
Bleomycin
Bleomycin is a glycopeptide antibiotic produced by the bacterium Streptomyces verticillus. Bleomycin refers to a family of structurally related compounds. When used as an anticancer agent, the chemotherapeutical forms are primarily bleomycin A2 and B2. It works by causing breaks in DNA...
, ramoplanin
Ramoplanin
Ramoplanin is a glycolipodepsipeptide antibiotic drug derived from strain ATCC 33076 of Actinoplanes.-Mechanism:It exerts its bacteriocidal effect by inhibiting cell wall biosynthesis, acting by inhibiting the transglycosylation step of peptidoglycan synthesis.-Uses:Its development has been...
, and decaplanin.
Mechanism
This class of drugs inhibit the synthesis of cell walls in susceptible microbes by inhibiting peptidoglycanPeptidoglycan
Peptidoglycan, also known as murein, is a polymer consisting of sugars and amino acids that forms a mesh-like layer outside the plasma membrane of bacteria , forming the cell wall. The sugar component consists of alternating residues of β- linked N-acetylglucosamine and N-acetylmuramic acid...
synthesis. They bind to the amino acids within the cell wall preventing the addition of new units to the peptidoglycan. In particular, they bind to acyl-D-alanyl-D-alanine in peptidoglycan.
Use
Due to their toxicity, their use is restricted to those patients critically ill or with a demonstrated hypersensitivity to the β-lactamsBeta-lactam
A β-lactam ring, is a four-membered lactam. It is named as such, because the nitrogen atom is attached to the β-carbon relative to the carbonyl...
. Effective against principally gram-positive cocci, they exhibit a narrow spectrum of action, and, while they are bacteriostatic against most species, they are bacteriocidal only against the enterococci. Some tissues are not penetrated very well by glycopeptides, and they do not penetrate into the CSF
Cerebrospinal fluid
Cerebrospinal fluid , Liquor cerebrospinalis, is a clear, colorless, bodily fluid, that occupies the subarachnoid space and the ventricular system around and inside the brain and spinal cord...
.
History
Glycopeptides used to be the last effective line of defenseDrug of last resort
Drugs of last resort are drugs only used when all other options are exhausted. Many of the best known are antibiotics, antivirals, or chemotherapy agents. In those cases, they have the most potent antibiotic, antiviral, or anticancer effects, and/or are drugs for which no resistant strains are...
for cases of Methicillin-resistant Staphylococcus aureus, however several newer classes of antibiotics, including linezolid
Linezolid
Linezolid is a synthetic antibiotic used for the treatment of serious infections caused by Gram-positive bacteria that are resistant to several other antibiotics...
of the oxazolidinone class, and daptomycin
Daptomycin
Daptomycin is a novel lipopeptide antibiotic used in the treatment of certain infections caused by Gram-positive organisms. It is a naturally occurring compound found in the soil saprotroph Streptomyces roseosporus. Its distinct mechanism of action means that it may be useful in treating infections...
of the lipopeptide class have proven to have activity against MRSA. Vancomycin-resistant staphylococcus aureus has been seen in some countries.
While not approved for use in the U.S., teicoplanin was discovered in the early 1990s and is marketed in Europe. It is more lipophillic than vancomycin, as it has more fatty acid chains. It is considered to be 50 to 100 times more lipophillic than vancomycin. Teicoplanin has an increased half-life compared to vancomycin, as well as having better tissue penetration. It can be two to four times more active than vancomycin, but it does depend upon the organism. Teicoplanin is more acidic, forming water-soluble salts, so it can be given intramuscularly. Teicoplanin is much better at penetrating into leucocytes and phagocytes than vancomycin.
Research
Several derivatives of vancomycin are currently being developed, including oritavancinOritavancin
Oritavancin is a novel semi-synthetic glycopeptide antibiotic being developed for the treatment of serious Gram-positive infections...
and dalbavancin
Dalbavancin
Dalbavancin is a novel second-generation lipoglycopeptide antibiotic. It belongs to the same class as vancomycin, the most widely-used and one of the few treatments available to patients infected with methicillin-resistant Staphylococcus aureus .Dalbavancin is a novel semisynthetic...
. Possessing longer half-lives than vancomycin, these newer candidates may demonstrate improvements over vancomycin due to less frequent dosing and activity against vancomycin-resistant bacteria.
Administration
Vancomycin is usually given intravenously, as an infusion, and can cause tissue necrosisNecrosis
Necrosis is the premature death of cells in living tissue. Necrosis is caused by factors external to the cell or tissue, such as infection, toxins, or trauma. This is in contrast to apoptosis, which is a naturally occurring cause of cellular death...
and phlebitis
Phlebitis
Phlebitis is an inflammation of a vein, usually in the legs.When phlebitis is associated with the formation of blood clots , usually in the deep veins of the legs, the condition is called thrombophlebitis...
at the injection site if given too rapidly. Pain at site of injection is indeed a common adverse event. One of the side-effects is Red man syndrome, an idiosyncratic reaction to bolus, caused by histamine release. Some other side-effects of vancomycin are nephrotoxicity including renal failure and interstitial nephritis, blood disorders including neutropenia, and deafness, which is reversible once therapy has stopped. Oral preparations are available, however they are not absorbed from the lumen of the gut, so are of no use in treating systemic infections. The oral preparations are formulated for the treatment of infections within the Gastro-Intestinal tract, Clostridium difficile
Clostridium difficile
Clostridium difficile , also known as "CDF/cdf", or "C...
, for example. Over 90% of the dose is excreted in the urine, therefore there is a risk of accumulation in patients with renal impairment, so therapeutic drug monitoring (TDM) is recommended.