Vancomycin is an antibiotic used to treat infections caused by gram-positive bacteria like Staphylococcus aureus and enterococci. However, some bacteria have evolved resistance to vancomycin, including vancomycin-resistant Staphylococcus aureus (VRSA) and vancomycin-resistant enterococci (VRE). VRSA infections are rare but serious, while VRE is more common and can cause intestinal infections and persist on surfaces. Treatment options for these resistant bacteria include linezolid, daptomycin, and tigecycline. Proper hygiene and limiting antibiotic use are important for controlling the spread of vancomycin-resistant infections.

1. Vancomycin-resistant bacteria: VRSA and VRE
What is Vancomycin?
Vancomycin is a glycopeptide antibiotic that is used to treat bacterial infections in the intestinal
tract caused by Clostridium difficile and Staphylococcus infections and Enterococcus spp that
cause inflammations in the large and small intestines.
It can be administered in two ways, orally and intravenously. Oral administration targets the
intestinal lining since the antibiotic is not absorbed into the body. Vancomycin treats several
infections including:
 Staphylococcal Enterocolitis, an infection caused by Staphylococcus aureus (inclusive of
Methicillin-Resistant strains of Staph. aureus
 Clostridium difficile associated diarrhea
 Infective Endocarditis, with isolates of Methicillin-Resistant Staphylococcus
aureus (MRSA), viridans group streptococci, Streptococcus
gallolyticus, Enterococcus spp, and Corynebacterium spp.
 Septicemia caused by MRSA, Methicillin-susceptible staphylococci in penicillin-allergic
patients or patients with failed response to antimicrobial therapies
 Bone infections caused by MRSA
 Lower Respiratory tract infections caused by MRSA and Lower respiratory tract infections
that have failed to respond to other forms of therapies
 Preoperative antimicrobial prophylaxis i.e gastrointestinal and genitourinary procedures
 surgical prophylaxis
Mechanism of Action of Vancomycin
Vancomycin acts against gram-positive and gram-negative bacteria, but majorly against gram-
positive bacteria. The gram-positive bacterial cell was a thick layer made up of peptidoglycan
linings. Peptidoglycan is made up of several amino-acid building blocks of NAM ( N-
acetylmuramic acid) and NAG (N-acetylglucosamine). The cross-linking of these amino acids
makes it very strong. Therefore, the mechanism of the vancomycin antibiotic is to act against the
synthesis of the peptidoglycan layer by binding to the D-Alanyl-D-alanine (D-ala-D-ala) terminal
of the synthesized peptide chain during cell- wall synthesis, inhibiting the action of transpeptidase,
preventing further elongation and cross-linking of the peptidoglycan matrix (twedweb.tulane.edu).
Why Vancomycin Resistance?
Bacteria have evolved over time for decades now, making them unsusceptible or insensitive to
antibiotic mechanisms, leading to the rise of the Antimicrobial resistance era.
Vancomycin antibiotic has been used for the treatment of Gram-positive and gram-negative
bacterial infection but has proved to be much more effective against Gram positives.
The bacterial evolution in this antibiotic era has led to antibiotic resistance, and in this case,
bacterial infections that were highly susceptible to vancomycin, have evolved majorly by causing
mutations in the transcriptase enzyme, associated with peptidoglycan synthesis and (where the
vancomycin mechanism is initiated), thus hindering its mechanisms, hence development of

2. resistant to vancomycin. Resistance to vancomycin was discovered in enterococci in the 1980s,
and this finding elicited significant concern with regard to the future use of vancomycin as an
effective treatment for MRSA.
Vancomycin-Resistant bacteria
a. Vancomycin-resistant Staphylococcus aureus (VRSA)
Fig. 1: Staphylococcus aureus on Blood agar (Source: https://live.staticflickr.com/)
These refer to the strains of Staphylococcus aureus that have become resistant antibiotic
glycopeptides (vancomycin).
S. aureus is notorious for its ability to acquire and develop resistance to antibiotics, and because
of the high prevalence rates of Staphylococcal infections, treatment regimes have been threatened.
Penicillin and methicillin were the first drugs of administration against Staphylococcus
aureus infections but the bacteria eventually evolved and became resistant to them. Vancomycin
was then used to treat the MRSA and over time, vancomycin has proven effective in treating severe
MRSA infections, a type of Staph. aureus infection that is highly resistant to Methicillin
antibiotics. Although Staphylococcus aureus has developed intermediate resistance to
vancomycin, the ability of S. aureus to become completely resistant to vancomycin is
disconcerting. Fortunately, strains that have complete resistance to vancomycin (VRSA) are rare,
despite the wide use of vancomycin for treatment of severe MRSA infections.

3. However, S. aureus clinical isolates with reduced susceptibility to vancomycin, and less
commonly, with complete resistance to vancomycin have emerged within the past 20 years.
There are three classes of vancomycin-resistant S.aureus (VRSA) that have emerged.
1. High-level VRSA,
2. Vancomycin-intermediate S.aureus (VISA)
3. Heterogeneous VISA (hVISA).
VISA infection was firstly identified in Japanese hospitals and later the strain of bacteria was also
found in the Asian region. VRSA infection is usually reported in people having a weakened
immune system or to those who are taking vancomycin for a longer duration. The infection is also
seen in those people who have undergone surgical procedures
b.Vancomycin-Resistant Enterococci (VRE)
Fig. 2: Image of Enterococcus faecalis on Chromogenic agar (Source:
https://live.staticflickr.com/)
Enterococci are coccoid or ovoid, gram-positive bacteria that can live within the digestive tract of
humans. The use of broad-spectrum antibiotics (vancomycin, cephalosporins, and metronidazole)
eliminated normal gut bacteria and has promoted the emergence of VRE.
Enterococci infections are among the most common types of infections acquired by hospitalized
patients.
VRE is transmitted from person to person most commonly by healthcare workers whose hands
have unintentionally become contaminated, either from feces, urine, or blood of a person carrying

4. the organism. It can also be spread indirectly via hand contact with open wounds or by touching
contaminated environmental surfaces, where the bacterium can survive for weeks.
Enterococci, generally, are incapable of causing disease than Staphylococcus but they can
complicate and prolong hospital stay. These Enterococcus infections that result in human disease
can be fatal, particularly those caused by strains of vancomycin-resistant enterococci (VRE) and
they can persist for up to 60 minutes on hands and as long as 4 months on surfaces.
Enterococcus faecium and Enterococcus faecalis are the most common VREs with E.
faecium being the most frequent species of VRE found in hospitals.
VRE can also be acquired through contact with pets and from food-producing animals. Colonized
individuals can bring VRE into health care settings
Some of the risk factors for acquiring VRE include:
 Immunosuppressed individuals such as Diabetes patients, elderly persons
 Exposure to antimicrobials for long periods of time, previous treatment with vancomycin
with a combination of other antibiotics and long hospital stays with antibiotic treatment.
 Immunocompromised- individuals with weakened immune systems like patients in the
ICU, cancer, and transplant wards
Enterococci have two types of resistance to vancomycin: acquired resistance from other bacteria
in the intestinal tract and intrinsic resistance, naturally harbored by the bacteria.
Clinical manifestations of VRE
The symptoms of VRE infection vary according to the site of infection. If VRE has invaded the
Infection of VRE in the bloodstream (Sepsis), manifestations of fever, Arrhythmia, and sickly
feeling. Severe infection, patients will have low blood pressure, causing shock although, it’s
uncommon.
It may manifest as urinary infections (UTI), with symptoms of pain and burning sensation during
urination and frequent urination, back pain. In rare cases, meningitis can cause headaches, stiff
neck, and confusion, with fever. VREs can also cause endocarditis with prolonged sepsis and may
cause the valve to leak or fail. Endocarditis is more common if the patient already has a damaged
heart valve or an artificial valve. Infected wounds are inflamed, with red and warm skin, soreness,
swelling, and contain pus or have pus drainage. VRE can also cause Pneumonia with symptoms
of fever, difficulty breathing, and coughing.
Treatment of Vancomycin-Resistant Bacteria
Treatment of Vancomycin Intermediate Staphylococcus aureus (VISA) is Linezolid, Ceftobiprole,
daptomycin, tigecycline, and others are the major drugs prescribed for the treatment of VISA
infection.
Vancomycin-Resistant Staphylococcus aureus (VRSA) infections can be treated with various
commercially available antibiotics, however, the most efficient way of controlling the spread of
VRSA is maintaining basic hygienic conditions such as proper wound care, washing hands before
while contacting directly with the patients and use of disposable gloves.
For the treatment of Vancomycin-Resistant Enterococci (VRE), Linezolid, daptomycin,
tigecycline, oritavancin, telavancin, quinupristin-dalfopristin, and teicoplanin are antimicrobials

5. that have been used with success against various VRE strains. Other procedures can augment the
antimicrobial treatment of VRE-infected patients such as exudation of pus from wounds and
abscess, removal of urinary catheters and intravenous lines.
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 https://live.staticflickr.com/
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Vancomycin-resistant bacteria: VRSA and VRE