Description

Vancomycin is a glycopeptide antibiotic. It is a large, complex molecule that is used to treat serious bacterial infections, particularly those caused by Gram-positive bacteria that are resistant to other drugs. The “HCl” in its name refers to the hydrochloride salt form, which is used for stability and solubility. Vancomycin is not absorbed well from the gut, so it’s administered differently depending on the infection. It’s typically given intravenously for systemic infections and orally for infections confined to the gastrointestinal tract.

Indications

Vancomycin is a crucial “last-resort” antibiotic for many serious infections. Its use is generally restricted to prevent the development of widespread bacterial resistance.

• Intravenous (IV) Administration: The primary use of IV vancomycin is to treat severe, systemic infections caused by Gram-positive bacteria, especially those resistant to other antibiotics. This includes:
  • Methicillin-resistant Staphylococcus aureus (MRSA) infections, such as those causing septicemia (blood poisoning), endocarditis (infection of the heart lining), bone and joint infections, and complicated skin and soft tissue infections.

• • Serious infections in patients with a serious allergy to penicillin.
  • Infections caused by other multi-drug resistant Gram-positive organisms, such as Vancomycin-resistant Enterococcus (VRE), though this use has limitations as VRE has developed resistance to vancomycin.
• Oral Administration: Because vancomycin is poorly absorbed from the gut, oral administration is only effective for treating infections within the intestines. Its main indication is for Clostridioides difficile-associated diarrhea (C. diff), also known as pseudomembranous colitis, and staphylococcal enterocolitis.

Mechanism of Action

Vancomycin’s mechanism of action is unique, making it effective against bacteria that have developed resistance to beta-lactam antibiotics like penicillin. It works by inhibiting a crucial step in the synthesis of the bacterial cell wall, a structure essential for the bacteria’s survival.

1. Binding to Peptidoglycan Precursors: Vancomycin does not directly inhibit an enzyme, but instead acts like a “cap” by binding with high affinity to the terminal D-alanyl-D-alanine portion of the peptidoglycan precursors. Peptidoglycan is the main component of the bacterial cell wall.
2. Blocking Transglycosylation and Transpeptidation: The binding of vancomycin to these precursors sterically hinders the enzymes (transglycosylases and transpeptidases, also known as penicillin-binding proteins or PBPs) from adding new units and cross-linking the peptidoglycan chains.

3. Weakening the Cell Wall and Causing Lysis: By preventing the formation of a strong, cross-linked cell wall, vancomycin causes the existing cell wall to become unstable. The bacterial cell, unable to withstand the internal osmotic pressure, swells and eventually ruptures (lyses), leading to cell death.

This specific binding site is the reason vancomycin is effective against resistant bacteria, and it’s also the basis for how some bacteria, like VRE, have become resistant: they have a mutation that changes the D-alanyl-D-alanine terminal to D-alanyl-D-lactate, which significantly reduces vancomycin’s binding affinity.