Vancomycin Sensitive S. aureus, VISA and VRSA
Most Staphylococcus aureus strains are sensitive to antibiotic vancomycin. The concentration of vancomycin required to inhibit these strains (minimal inhibitory concentration – MIC) is 0.5-2 micrograms/mL. S. aureus strains for which vancomycin MICs are 4-8 micrograms/mL are classified as Vancomycin Intermediate Staphylococcus aureus – VISA, and strains for which vancomycin MICs is equal or exceeds 16 micrograms/mL are classified as Vancomycin Resistant Staphylococcus aureus – VRSA (1).
Importance of VRSA
VRSA is sensitive only to few antibiotics, and even these might become ineffective through time, since antibiotic resistance is continuously developing among staphylococci. However, to date, all VISA and VRSA isolates have been sensitive to some antibiotic (2).
VISA/VRSA infections are still rare.
In May 1996, the first case of VISA was reported in Japan. A four month old boy became infected after heart surgery, unsuccessfully treated with vancomycin for 29 days, and then finally cured with a combination of antibiotics (6). Later, VISA cases were reported from United States, France, England, Hongkong, and so on. 17 cases of VISA infection have been reported to date in the United States (4).
As of September 2006, 6 cases of VRSA infection (Michigan 2002, Pennsylvania 2002, New York 2004, and 3 from Michigan in 2005) have been reported in the United States (4).
Risk Factors for VISA and VRSA infections
Persons that developed VISA or VRSA infections had one or more of the following underlying health conditions (2):
- Diabetes or a kidney disease
- Previous infections with MRSA
- Intravenous catheters
- Recent hospitalization
- Recent treatment with vancomycin or other antibiotic
Mechanisms of Resistance in VRSA and VISA
All VRSA bacteria to date contained vanA gene. Most VRSA-positive patients had a history of infections caused by both MRSA and Vancomycin Resistant Enterococci (VRE) containing vanA gene. It seems that the vanA gene was transferred via plasmids from the VRE to the MRSA strain, resulting in the VRSA.
VISA bacteria have thicker cell walls than vancomycin sensitive staphylococci, obstructing vancomycin binding to bacterial cell membrane and thus reducing its effect.
Not all susceptibility testing methods detect VISA or VRSA isolates. FDA approved tests for VRSA include (1):
Reference broth microdilution (VRSA and VISA)
Agar dilution (VRSA and VISA)
Etest® (VRSA and VISA)
MicroScan® overnight and Synergies plus™ (VRSA)
BD Phoenix™ system (VRSA)
Disk diffusion (VRSA)
Vancomycin screen agar plate – brain heart infusion (BHI) agar (VRSA)
Antibiotics Effective Against VRSA
There is no official list of antibiotics effective against VRSA to date, so antibiotic susceptibility test should be made on each infected sample.
Trimethroprim/sulfamethoxazole was effective in a patient with first recognized VRSA infection in US in 2002 (8).
Linezolid, Quinupristin/dalfopristin and Daptomycin “can be considered in treatment of VISA and VRSA” (7,8).
Tigecycline was found to be active against VISA (8).
Ceftobiprole, tested on Rockefeller University New York/US in 2008 was effective against MRSA and VRSA (5).
VISA and VRSA Cases Should be Reported
Laboratories should save all VISA and VRSA isolates and send them to local health departments for confirmatory testing.
VRSA and Immunity
Infections with VRSA can recur. There is no vaccine that can prevent VRSA infection (3).
- VISA and VRSA definition (cdc.gov)
- VISA/VRSA treatment (cdc.gov)
- VRSA FAQ (vdh.state.va.us)
- VRSA cases (dsf.health.state.pa.us)
- Ceftobiprole (eurekalert.org)
- The first VRSA case in 1966 in Japan (science.education.nih.gov)
- Quinupristin and dalfopristin (pubmedcentral.nih.gov)
- Trimetoprim-sulphametoxazole was effective in VRSA (cdc.gov)