Drug resistant microbes have become a major public health concern. Some microbes are not only resistant to older generation antibiotics due to overuse and incorrect use, but are now also showing resistance to new generation antibiotics. This has taken the form of extreme drug resistance and the term ‘superbug’ has taken on a new meaning these days. It has also prompted the use of antibiotics that were not commonly prescribed due to toxicity in an attempt to treat infections that are cause by drug-resistant bacteria.
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 to or exceeds 16 micrograms/mL are classified as Vancomycin Resistant Staphylococcus aureus – VRSA (1).
Danger of VRSA
As with any drug-resistant bacteria, there is a danger of complications if a person contracts a bacterial infection where antibiotic therapy is ineffective. Death is even a possibility. Fortunately VRSA is still sensitive to a few antibiotics. However, these might become ineffective with time since antibiotic resistance is continuously developing among staphylococci.
VISA/VRSA infections are rare. In May 1996, the first case of VISA was reported in Japan. A four month old boy became infected after heart surgery and was unsuccessfully treated with vancomycin for 29 days. Thereafter he was cured with a combination of antibiotics (6). Later, VISA cases were reported in nations such as the United States, France, England, Hong Kong, and other. 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
Based on reports, people that have 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
However, there may be other risk factors that can also increase the likelihood of contracting these infections. As with most drug-resistant bacterial infections, there is often a history of severe illness, surgery and/or hospitalization. In addition, HIV infection and AIDS has further complicated the management of drug-resistant bacterial infections as a person does not have sufficient immune defenses to overcome the infection completely. Children and the elderly are particularly at risk even without pre-existing diseases that may compromise the immune system.
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 appears 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. These thicker walls obstruct vancomycin from binding to the bacterial cell membrane. As a result, the drug is unable to act as it normally would to destroy the bacteria, which is to inhibit cell wall synthesis.
VRSA symptoms are essentially the same as symptoms caused by regular Staphylococcus aureus. The symptoms depends on the area that is infected and how the infection may spread. It therefore may range from mild skin infections to life threatening sepsis and infections of internal organs. The latter occurs when the bacteria spreads to the bloodstream and distant organs, particularly if treatment is delayed or the bacteria are not responding to antibiotics.
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 an antibiotic susceptibility test should be done 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).
It is essential that patients using antibiotics are properly educated about its use. This applies to all people using antibiotics but more so to individuals who are undergoing treatment for drug-resistant bacteria. The entire course of antibiotics needs to be completed (if taken orally), and the medication should be taken at the prescribed times everyday.
Failure to adhere to the prescription can further complicate the case as the bacteria may become less sensitive to the only remaining antibiotics that can treat these drug-resistant infections. Never change the dosage or stop the antibiotics early because there is an improvement of symptoms. Always speak to a medical professional if any side effects arise but do not discontinue antibiotic use unless otherwise advised.
VISA and VRSA Cases Should be Reported
Drug resistance is notifiable to relevant health authorities and relevant government agencies. Laboratories should save all VISA and VRSA isolates and send them to local health departments for confirmatory testing. This allows health authorities to track the spread of these drug-resistant bacteria and formulate appopriate treatment protocol for future cases.
VRSA and Immunity
As with any infection, VRSA infections can recur. There is no vaccine that can prevent VRSA infection (3). It is important to note that while the appropriate antibiotic is effective in halting the progression of the infection and reducing bacterial populations in the infected host, resolution of an infection also relies on a healthy immune system. Therefore people with a weakened immune system are particularly at risk of serious complications and even death due to drug-resistant bacteria.
- 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)