Vancomycin, a glycopeptide antibiotic, is generally reserved for serious infections caused by specific types of bacteria. Its effectiveness against Gram-Positive Cocci (GPC), a major group of disease-causing microorganisms, is well-established. Vancomycin is considered an effective tool for combating these infections, particularly when other common treatments have failed.
Understanding the Targets: Gram-Positive Cocci
Gram-Positive Cocci are spherical bacteria identified by the Gram stain test, which causes them to appear purple or blue under a microscope. They possess a unique cell wall structure characterized by a thick, multilayered structure composed primarily of peptidoglycan. This substantial outer layer, which can be up to 80 nanometers thick, provides the bacteria with physical protection.
The dense peptidoglycan layer makes Gram-Positive bacteria susceptible to Vancomycin. Conversely, Gram-Negative bacteria have a thin peptidoglycan layer shielded by an outer membrane, preventing the large Vancomycin molecule from reaching its target. Common examples of GPC that cause human infection include Staphylococcus species (such as Staphylococcus aureus), Streptococcus species, and Enterococcus species.
Vancomycin’s Mechanism of Action
Vancomycin kills bacteria by interfering with the construction of the peptidoglycan cell wall. This wall is built from repeating sugar chains connected by amino acid bridges to form a strong, cross-linked mesh. The final step involves linking precursor units that end in the amino acid pair D-alanyl-D-alanine (D-Ala-D-Ala). Vancomycin is a large molecule that tightly binds to this D-Ala-D-Ala terminus on the cell wall building blocks.
By binding to the precursors, Vancomycin acts as a physical barrier, blocking the enzymes responsible for linking the chains together. It prevents the transpeptidation and transglycosylation reactions necessary for cross-linking the peptidoglycan strands into a rigid structure. When cross-links cannot form, the cell wall remains weak as the bacterium attempts to grow and divide. This weakened cell wall ruptures due to high internal pressure, leading to the death of the microorganism.
Specific Organism Coverage
Vancomycin is utilized against a range of Gram-Positive Cocci, often preferred for infections unresponsive to common antibiotics. Its most recognized use is treating serious systemic infections caused by Methicillin-Resistant Staphylococcus aureus (MRSA). MRSA has developed resistance to penicillin-like antibiotics, making Vancomycin an alternative for conditions like septicemia, endocarditis, and pneumonia. For these infections, Vancomycin must be administered intravenously (IV) to ensure sufficient concentration in the bloodstream and infected tissues.
The medicine is also effective against susceptible strains of Streptococcus species, including Streptococcus pneumoniae, which causes pneumonia and meningitis. Vancomycin is sometimes used for Streptococcus strains resistant to penicillin. For Enterococcus infections, it remains an option for susceptible strains, although the emergence of resistance is a concern.
A unique application of Vancomycin is the treatment of Clostridioides difficile infection, which causes severe diarrhea and colitis. Although C. difficile is a Gram-Positive rod-shaped bacterium, it is a common target for Vancomycin treatment. For this intestinal infection, Vancomycin is administered orally, not intravenously, because it is poorly absorbed into the bloodstream. Oral administration allows the antibiotic to concentrate in the gastrointestinal tract and act directly on the bacteria.
The Challenge of Vancomycin Resistance
The effectiveness of Vancomycin is threatened by the development of bacterial resistance. This has led to the emergence of strains that survive exposure, most notably Vancomycin-Resistant Enterococci (VRE) and, less commonly, Vancomycin-Resistant Staphylococcus aureus (VRSA). These resistant bacteria acquire genetic material that alters the structure of their cell wall precursors. The resistance mechanism involves a biochemical modification of the Vancomycin binding site, the D-Ala-D-Ala terminus.
Resistant bacteria produce enzymes that change the D-Ala-D-Ala pair to D-alanyl-D-lactate (D-Ala-D-Lac). This substitution replaces a nitrogen atom with an oxygen atom, significantly reducing Vancomycin’s binding affinity to the precursor. Since Vancomycin cannot tightly bind and block cross-linking, the bacteria successfully complete the construction of their protective cell wall, surviving treatment. The spread of these resistant organisms limits treatment options and emphasizes the need for careful antibiotic use.