Glycopeptide antibiotics
Glycopeptide antibiotics are a class of antibiotics that include glycosylated cyclic peptides, primarily used to treat infections caused by gram-positive bacteria. These antibiotics work by inhibiting the synthesis of bacterial cell walls, making them crucial for addressing severe infections, especially when other treatments have failed. Vancomycin, the first glycopeptide discovered in 1956, remains the most widely used member of this class. However, newer alternatives like teicoplanin offer improved tissue penetration and a longer half-life. Glycopeptides are particularly valuable for patients allergic to beta-lactam antibiotics. Despite their effectiveness, they have limitations, including potential side effects such as pain at injection sites and the risk of red man syndrome. Additionally, some bacterial strains have developed resistance to these antibiotics, posing challenges in treatment. Ongoing research aims to enhance our understanding of their mechanisms and to develop new compounds within this antibiotic class.
Glycopeptide antibiotics
Definition
Glycopeptide antibiotics are a class of antibiotics that contains glycosylated cyclic peptides and are used to treat infections. Glycopeptide antibiotics inhibit the synthesis of the cell walls of the gram-positive bacteria that cause many infections. Traditionally, this class of antibiotics has been used as a last line of defense to treat life-threatening infections after other treatments have failed.
Class Members
The first glycopeptide discovered was vancomycin in 1956, followed by US Food and Drug Administration approval in 1958. Vancomycin has been the most widely used of this class, but more effective alternatives from this class have been developed. The most useful of these newer members is teicoplanin, which has a more effective ability to penetrate tissues; it also has a longer half-life. Other antibiotics in this class include bleomycin, brevianamide A and B, and oritavancin.
Mode of Action
The members of this class of drugs bind tightly to the amino acid residue of acyl-D-alanyl-D-analine, located on the terminus of the pentapeptide peptidoglycan of several strains of gram-positive bacteria. This specific binding action of the drug prevents the bacteria from synthesizing their cell walls, thereby inhibiting their ability to cause an infection.
Ongoing research methods that include the sequencing and biosynthesis of gene clusters are part of the continued study of the mode of action of glycopeptides and part of the development of new members of the class. These research methods require the growth of bacterial cultures, isolation of their genomic deoxyribonucleic acid (DNA), cloning of the DNA fragments, identification of positive clones by using southern hybridization, and construction of libraries, which are screened using the polymerase chain reaction (PCR) technique. This analysis of gene clusters allows for identification of the specific genes that directly cause the binding of an antibiotic and for identification of the specific genes that can lead to drug resistance.
Side Effects, Complications, and Limitations
The glycopeptides cannot enter all tissues and, therefore, cannot treat infection in all tissues. Because of this, scientists were studying glycopeptides to see if they could be modified to treat "superbugs," infections caused by resistant pathogens.
Vancomycin, the most common glycopeptide, is most effective when delivered intravenously, so pain and irritation can occur at the injection site and lead to what is known as red man syndrome; in turn, this can lead to blood disorders. Some bacterial strains can become resistant to the glycopeptide antibiotics.
Impact
Members of the glycopeptide antibiotic class of drugs have become indispensable in treating infectious diseases. The ability of glycopeptides to be effective even with only once-daily or twice-daily dosing has led to their application as an out-of-hospital therapy to treat infections that have been resistant to other classes of drugs. The glycopeptide antibiotic class is especially useful as an alternative to the beta-lactam antibiotic class for persons who are sensitive to that class of drugs.
Bibliography
Finch, Robert G., and George M. Eliopoulos. “Safety and Efficacy of Glycopeptide Antibiotics.” Journal of Antimicrobial Chemotherapy 55 (2005): ii5-ii13.
Gould, Ian M., and Jos W. M. Van der Meer. Antibiotic Policies: Fighting Resistance. New York: Springer, 2007.
Nagarajan, Ramakris. Glycopeptide Antibiotics. West Palm Beach, Fla.: CRC Press, 1994.
Sanford, Jay P., et al. The Sanford Guide to Antimicrobial Therapy. 18th ed. Sperryville, Va.: Antimicrobial Therapy, 2010.
Tian, Li, et al. "Newest Perspectives of Glycopeptide Antibiotics: Biosynthetic Cascades, Novel Derivatives, and New Appealing Antimicrobial Applications." World Journal of Microbiology and Biotechnology, vol. 39, no. 67, 3 Jan. 2023, doi.org/10.1007/s11274-022-03512-0. Accessed 3 Feb. 2025.
Uwe, Frank, and Evelina Tacconelli. The Daschner Guide to In-Hospital Antibiotic Therapy. New York: Springer, 2009.
Walsh, Christopher. Antibiotics: Actions, Origins, Resistance. Washington, D.C.: ASM Press, 2003. Examines such topics as how antibiotics block specific proteins, how the molecular structure of drugs enables such activity, the development of bacterial resistance, and the molecular logic of antibiotic biosynthesis.