Vancomycin is a glycopeptide antibiotic reserved for treating severe bacterial infections. It targets only Gram-Positive bacteria by interfering with the construction of the bacterial cell wall. This specific function makes it important for treating organisms resistant to more common antibiotics.
Understanding Gram-Positive and Gram-Negative Bacteria
Bacteria are broadly categorized into two groups based on the structure of their cell envelopes. Gram-positive bacteria possess a thick, multi-layered cell wall composed primarily of peptidoglycan, which can be 20 to 80 nanometers thick.
Gram-negative bacteria have a different cell envelope structure. They feature a thin layer of peptidoglycan, typically 2 to 7 nanometers thick, situated between two membranes. This delicate layer is protected by an outer membrane composed of lipopolysaccharide (LPS) that forms a physical barrier.
How Vancomycin Targets Bacterial Cell Walls
The mechanism of Vancomycin targets the synthesis of the peptidoglycan layer that gives the bacterial cell wall its strength. Vancomycin binds to the D-Ala-D-Ala terminus of the peptidoglycan precursors. This binding, stabilized by five hydrogen bonds, physically blocks the transpeptidase enzyme from cross-linking the peptidoglycan chains.
By preventing this cross-linking, the drug weakens the cell wall structure, leading to rupture and cell death. The thick, exposed peptidoglycan of Gram-positive bacteria allows Vancomycin to reach its target easily. However, the molecule is large, with a molecular weight of around 1,500 Daltons.
The large size of Vancomycin is the primary reason it is ineffective against Gram-negative organisms. The outer lipopolysaccharide membrane acts as a selective filter, containing small channels called porins. Since most porins only permit molecules smaller than approximately 600 Daltons to pass through, the Vancomycin molecule is physically blocked from reaching the thin peptidoglycan layer.
Primary Uses in Modern Medicine
Vancomycin’s specific activity against Gram-positive organisms makes it a reserved medication for treating serious infections. It is frequently employed against multidrug-resistant bacteria, most notably Methicillin-Resistant Staphylococcus aureus (MRSA), which often causes severe bloodstream, skin, and bone infections. For systemic infections, the drug is typically administered intravenously to ensure it reaches the site of infection throughout the body.
A primary clinical indication is the treatment of Clostridium difficile (C. diff) infection, which causes severe diarrhea and colitis. For this, Vancomycin is given orally to deliver the drug directly to the bacteria in the gut, as it is poorly absorbed into the bloodstream. The emergence of resistance is a growing concern, highlighted by the development of Vancomycin-Resistant Enterococci (VRE). Careful stewardship of Vancomycin is required to preserve its effectiveness against susceptible organisms.

