Last Updated on January 25, 2020 by Sagar Aryal
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 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.
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.
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.
- High-level VRSA,
- Vancomycin-intermediate S.aureus (VISA)
- 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
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 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 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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