Vancomycin covers a broad range of gram-positive bacteria, including staphylococci, streptococci, enterococci, and several other important pathogens. It has no meaningful activity against gram-negative organisms. This gram-positive focus is what makes vancomycin a cornerstone antibiotic for serious infections caused by drug-resistant bacteria like MRSA.
How Vancomycin Works
Vancomycin kills bacteria by blocking cell wall construction. Gram-positive bacteria build their outer walls from a mesh-like material called peptidoglycan. To assemble this mesh, the bacteria link protein building blocks that end in a specific two-part sequence. Vancomycin locks onto that sequence using five hydrogen bonds, physically preventing the bacteria from completing their cell wall. Without a functional wall, the bacteria can’t survive.
This mechanism explains both vancomycin’s strengths and its blind spots. Any gram-positive organism that relies on this same wall-building process is vulnerable. Gram-negative bacteria, on the other hand, have an additional outer membrane made of fatty molecules that acts as a physical barrier. Vancomycin is simply too large to pass through the tiny channels in that membrane, so it never reaches its target.
Staphylococci, Including MRSA
Vancomycin’s most well-known role is treating infections caused by methicillin-resistant Staphylococcus aureus (MRSA). MRSA has developed resistance to the penicillin-family antibiotics that would normally be first-line treatment, but vancomycin bypasses that resistance entirely because it works through a different mechanism. It also covers methicillin-resistant Staphylococcus epidermidis (MRSE), a common cause of infections on implanted devices like prosthetic joints and heart valves.
Nearly all MRSA strains remain susceptible to vancomycin, though effectiveness depends on how easily the drug can inhibit a given strain. Strains that require higher concentrations of the drug to be killed are associated with higher treatment failure rates. In one large hospital survey, about 54% of MRSA strains were inhibited at the lowest effective concentration, while 44% required twice as much, a level still classified as susceptible but linked to worse clinical outcomes.
Streptococci and Pneumococci
Vancomycin is active against streptococcal species broadly, including group A and group B streptococci. It also covers Streptococcus pneumoniae, the leading cause of bacterial pneumonia and meningitis. This is particularly relevant for penicillin-resistant strains of pneumococcus, where vancomycin serves as a reliable backup. In bacterial meningitis, vancomycin is frequently part of the initial treatment regimen specifically to cover the possibility of a resistant pneumococcal infection.
Enterococci, With Important Exceptions
Vancomycin covers most enterococcal species, which commonly cause urinary tract infections, bloodstream infections, and wound infections in hospitalized patients. However, vancomycin-resistant enterococci (VRE) represent a major and growing exception.
VRE strains evade vancomycin by altering the target sequence on their cell wall building blocks. Instead of the normal two-part ending that vancomycin grips tightly, resistant strains swap in a slightly different molecule. This single substitution replaces one of the five critical hydrogen bonds with a repulsive force, dramatically reducing vancomycin’s ability to bind. Several genetic variants (labeled VanA through VanG) encode this resistance, with VanA and VanB being the most clinically significant. If you’re dealing with an enterococcal infection, the lab will specifically test whether the strain is vancomycin-susceptible before committing to treatment.
Clostridioides difficile
Oral vancomycin is the preferred treatment for Clostridioides difficile infection, the bacteria responsible for severe antibiotic-associated diarrhea and colitis. This use works differently from most vancomycin treatments. When taken by mouth, vancomycin is barely absorbed into the bloodstream. Instead, it stays in the gut, reaching high concentrations right where C. difficile lives.
For an initial episode, the standard approach is a 10-day oral course. For severe, fulminant infections, the dose is increased fourfold, and if the gut has stopped moving normally, vancomycin can also be delivered rectally to ensure it reaches the colon. First recurrences are typically treated with a tapered and pulsed regimen, gradually spacing out doses rather than stopping abruptly, which helps prevent the infection from bouncing back.
Other Gram-Positive Organisms
Beyond the major pathogens, vancomycin covers several less common but clinically important gram-positive bacteria:
- Listeria monocytogenes: A foodborne pathogen that causes serious illness in pregnant women, newborns, and immunocompromised individuals. Vancomycin is considered a second-line agent for listeriosis, and studies consistently show that all tested strains remain fully susceptible.
- Corynebacterium species: Particularly Corynebacterium jeikeium, which causes infections in immunocompromised patients and is often resistant to penicillin. Vancomycin is one of the few reliable options for these infections.
- Bacillus species: Including Bacillus cereus, which is naturally resistant to penicillin-type antibiotics. Vancomycin provides an alternative.
- Clostridium species: Beyond C. difficile, vancomycin has activity against other clostridia, which are anaerobic bacteria that can cause gas gangrene and other deep tissue infections.
Vancomycin also covers many gram-positive anaerobes found in the mouth, which can be relevant in mixed infections originating from dental or oral sources.
What Vancomycin Does Not Cover
Vancomycin has no useful activity against gram-negative bacteria. This includes common pathogens like E. coli, Klebsiella, Pseudomonas, Salmonella, and Neisseria. The outer membrane of gram-negative bacteria blocks vancomycin from reaching its target entirely. This is an inherent structural limitation, not a resistance mechanism the bacteria acquired over time.
Within the gram-positive world, the key gaps are VRE (discussed above) and rare strains of S. aureus with reduced vancomycin susceptibility. These intermediate-resistance strains (sometimes called VISA) and fully resistant strains (VRSA) are uncommon but do exist. For S. aureus, strains are classified as susceptible at concentrations of 2 micrograms per milliliter or below, intermediate at 4 to 8, and resistant at 16 or above.