What does it mean to be vancomycin resistant? An in-depth look

October 12, 2025 •

3 min read

Vancomycin-resistant enterococci (VRE) were responsible for an estimated 54,500 infections and 5,400 deaths among hospitalized U.S. patients in 2017, highlighting the serious public health challenge of what it means to be vancomycin resistant. This phenomenon is a prime example of the accelerating issue of antibiotic resistance globally.

Quick Summary

Vancomycin resistance is the ability of certain bacteria, like enterococci and Staphylococcus aureus, to survive treatment with the antibiotic vancomycin. It involves genetic changes that alter the bacterial cell wall, compromising the drug's effectiveness and complicating treatment options.

Key Points

Altered Cell Wall: The most common vancomycin resistance mechanism involves modifying the bacterial cell wall's precursor molecules, preventing vancomycin from binding effectively.
Key Organisms: Vancomycin-Resistant Enterococci (VRE) and Vancomycin-Resistant Staphylococcus aureus (VRSA/VISA) are the primary culprits of this form of antibiotic resistance.
Healthcare Threat: Most vancomycin-resistant infections occur in healthcare settings among vulnerable patients due to prolonged antibiotic use, invasive devices, and weakened immune systems.
Diagnostic Challenge: Diagnosis requires specialized laboratory testing, including susceptibility testing and agar screening, to identify the level and mechanism of resistance.
Alternative Treatments: Since vancomycin becomes ineffective, alternative antibiotics like linezolid and daptomycin are used to treat infections, though options can be limited.
Prevention is Key: Controlling the spread of resistant organisms relies heavily on strict infection control measures, prudent antibiotic use (antimicrobial stewardship), and thorough hand hygiene.

What Is Vancomycin and Why Is Resistance a Concern?

Vancomycin is a powerful glycopeptide antibiotic, frequently used for treating serious infections caused by Gram-positive bacteria. It inhibits bacterial cell wall synthesis by binding to peptidoglycan precursors. The development of vancomycin-resistant bacteria is a major public health concern because it limits effective treatment options for serious infections, especially in healthcare settings.

The Mechanisms Behind Vancomycin Resistance

Bacteria develop vancomycin resistance through genetic changes that modify the drug's target or thicken the cell wall.

Genetic Alteration of the Target Site

High-level resistance often results from bacteria acquiring gene clusters, like vanA or vanB, which modify the cell wall precursor target from D-Ala-D-Ala to D-Ala-D-Lac or D-Ala-D-Ser. This significantly reduces vancomycin's binding affinity, making it ineffective.

Cell Wall Thickening (VISA/hVISA)

Staphylococcus aureus can develop intermediate resistance (VISA) or heterogeneous resistance (hVISA) through a thickened cell wall. This abnormal cell wall traps vancomycin, preventing it from reaching the active sites of cell wall synthesis.

The Culprits: VRE and VRSA

Vancomycin resistance is primarily associated with:

Vancomycin-Resistant Enterococci (VRE): Enterococci, normally in the intestines, can cause serious infections in vulnerable patients. VRE spreads via direct contact or contaminated surfaces in healthcare.
Vancomycin-Resistant Staphylococcus aureus (VRSA): VRSA is rare but concerning. It often acquires the vanA gene from VRE and is typically also methicillin-resistant, creating a multidrug-resistant organism.

Comparing VRE and VRSA


Feature	Vancomycin-Resistant Enterococci (VRE)	Vancomycin-Resistant Staphylococcus aureus (VRSA)
Mechanism	Primarily acquired `vanA` or `vanB` genes, altering cell wall precursors.	Acquired `vanA` gene from VRE (high-level) or chromosomal mutations causing cell wall thickening (intermediate).
Prevalence	Fairly common in healthcare settings.	Very rare.
Transmission	Direct contact, contaminated surfaces/equipment.	Similar to MRSA; contact is primary. Gene transfer from VRE is a key concern.
Associated Infections	UTIs, bloodstream infections, wound infections.	Potentially severe infections: sepsis, pneumonia, endocarditis.
Treatment Challenges	Fewer antibiotic options; alternatives like daptomycin or linezolid.	Extremely difficult; often requires combination therapy guided by testing.

Risk Factors for Developing a Vancomycin-Resistant Infection

Risk factors for acquiring vancomycin-resistant organisms in healthcare include prolonged or previous antibiotic use (especially vancomycin), extended hospital stays, weakened immune systems, presence of invasive medical devices, and prior VRE colonization.

Diagnosis and Treatment of Vancomycin Resistance

Diagnosis

Diagnosis involves taking a sample (e.g., blood, urine) for culture and susceptibility testing to identify the bacteria and effective antibiotics. Specialized tests screen for resistance levels in S. aureus.

Treatment

Treatment depends on the organism and susceptibility results. Alternatives for VRE may include linezolid, daptomycin, tigecycline, or fosfomycin. Removing the source of infection is also crucial. VRSA treatment is complex and requires guidance from an infectious disease specialist.

Preventing the Spread of Vancomycin Resistance

Preventing the spread relies on Antimicrobial Stewardship and infection control. Stewardship promotes appropriate antibiotic use, such as restricting vancomycin and using susceptibility testing. Infection control involves hand hygiene, contact precautions for VRE patients, and environmental cleaning. Patient education is also important.

Conclusion

Vancomycin resistance is a significant challenge in healthcare, stemming from bacterial evolution that bypasses the antibiotic's effects. The mechanisms, whether genetic modification or cell wall changes, highlight microbial adaptability. Combating this threat requires novel treatments, strict infection control, and responsible antibiotic use to manage infections and preserve antibiotic efficacy.

Learn more about antibiotic resistance from the CDC.

Frequently Asked Questions

Vancomycin is a powerful antibiotic, often considered a 'last resort' drug, used to treat severe infections caused by Gram-positive bacteria, including Methicillin-resistant Staphylococcus aureus (MRSA).

Bacteria can become resistant by acquiring specific genes (like the vanA or vanB clusters) that alter their cell wall's structure, causing vancomycin to lose its ability to bind and kill the cell. In other cases, bacteria like S. aureus can mutate to thicken their cell walls, physically blocking the drug.

The most common and clinically significant vancomycin-resistant bacteria are Vancomycin-Resistant Enterococci (VRE) and, much more rarely, Vancomycin-Resistant Staphylococcus aureus (VRSA).

Individuals at increased risk include people who have had long-term or frequent antibiotic treatment, especially with vancomycin, have extended hospital stays, have weakened immune systems, or use invasive medical devices like catheters.

While healthy people can be colonized with vancomycin-resistant bacteria without getting sick, they are at very low risk of developing a serious infection.

Treatment requires alternative antibiotics to which the bacteria are susceptible. These can include drugs like linezolid or daptomycin, depending on the specific organism and the infection site. Source control, like removing infected catheters, is also a critical part of treatment.

Prevention involves robust infection control practices in healthcare settings, including rigorous hand hygiene, isolation precautions for infected patients, proper environmental cleaning, and implementing antimicrobial stewardship programs to optimize antibiotic use.