A bug in Brazil: Is VRSA back with a vengeance?
To dismiss this as an anomaly would be unwise’
Though the health care continuum is currently under siege by a host of emerging gram negatives like CRE, at one time a much-feared single pathogen was thought to herald the arrival of the post-antibiotic era: Vancomycin-resistant Staphylococcus aureus (VRSA).
Sporadic cases of VRSA eventually occurred in the U.S., as MRSA infections appeared that were impervious to vancomycin — the mainstay drug against resistant staph strains for decades. But the vaunted superbug was not able to sustain itself and establish an endemic presence in hospitals or communities. Some theorized that the price of greater drug resistance in the microorganism was the loss of vigor and transmissibility, and the VRSA threat was largely forgotten.
Now we have this — an alarm blinking in Brazil, warning that VRSA is back and showing true threat potential. In answer to our first skeptical question about the finding, lead researcher Cesar Arias, MD, PhD, says, "To dismiss this as an anomaly would be unwise."
A professor of medicine and molecular genetics at the Houston-based University of Texas Health Science Center, Arias and colleagues conducted microbiological and genetic analyses of VRSA recovered from the blood of a 35-year-old Brazilian man. They identified a novel transferable plasmid that carries the genes necessary for vancomycin resistance. As noted in the case summary below, the VRSA isolate has genetic links to the widespread USA300 community strain and its vanA cluster plasmid could be easily transferred — and presumably confer resistance — to other staph strains.
"We report the case of a patient from Brazil with a bloodstream infection caused by a strain of methicillin-resistant Staphylococcus aureus (MRSA) that was susceptible to vancomycin but that acquired the vanA gene cluster during antibiotic therapy and became resistant to vancomycin," the authors reported.1 "Both strains are phylogenetically related to MRSA lineage USA300. A conjugative plasmid carrying the vanA cluster was identified and readily transferred to other staphylococci. The presence and dissemination of community-associated MRSA containing vanA could become a serious public health concern."
Two points jump out immediately from this summation — the potential for VRSA in the widely dispersed MRSA USA300 community strain, and the fact that the patient had a bloodstream infection instead of the soft tissue infections typical for VRSA.
"This is the first-ever reported bloodstream infection caused by a highly vancomycin-resistant MRSA bacteria," Arias says. "The fact that this was acquired as a bloodstream infection raises the question, has this bug now adapted and is it more able to carry these genetic resistance traits? We don’t know how widespread this plasmid is in Brazil."
The patient had a history of leg cellulitis and was admitted to a hospital in June 2012 with recurrent infections of the skin and soft tissues. Vancomycin and other antibiotics were used to treat recurrent symptoms while the patient remained in the hospital for treatment of skin cancer. On July 16 and 24, blood cultures yielded MRSA isolates that were susceptible to vancomycin, linezolid, and clindamycin. On August 15, however, fever recurred and blood cultures were positive for two MRSA isolates, one of which was resistant to vancomycin (minimal inhibitory concentration, > 32 μg per milliliter).
"This is a bloodstream infection coming straight from the soft tissue infection with the ability to cause severe infection in this case," Arias says. "So this is behaving as staph behaves, the acquisition of these [resistance components] did not appear to cause any problems in its pathogenic ability."
This strain is different’
Much like many of the first cases of VRSA, vancomycin resistance may have been transferred by a co-infecting vancomycin resistant enterococci (VRE) strain.
"It is possible the transposon that carried the resistance gene came from enterococci because we compared the sequence of the transposon — t is identical to the VRE that we isolated from the patient," Arias says. "However, the plasmid — which is the one that is carrying this transposon — it is not an enterococcal plasmid. This plasmid seems to be able to go into any staph and that could cause problems."
Given the genetic lineage identified, that would apparently include the USA300 community strain, which arose dramatically in the 1990s and has now displaced less hardy MRSA varieties in both the community and hospitals. In short, the story of VRSA is far from over.
"I don’t think so," Arias says. "Strains of VRSA have now popped up in the United states, in Europe, India, Iran and now in South America. Now it is true that there is no evidence that it has disseminated, but this strain is different from the others. The difference is that this strain is now in a genetic background that has previously been shown to be easily spread. This community-associated MRSA USA300 has become epidemic in the U.S. and also in South America. It has actually entered hospitals."
A USA300 strain of VRSA would certainly threaten hospital patients, but given its community origins could also cause infections in healthy people.
"The worst resistance possible has now appeared in [a] community-associated MRSA clone," says Barbara Murray, MD, co-author of the paper and director of the Division of Infectious Diseases at the UTHealth Medical School. "There will have to be increased surveillance in South America and worldwide in the future."
There are a few other possible drug options (i.e.,linezolid) against VRSA.
"We have options, but the problem is the options are more expensive — we will be hard pressed to find [options] equivalent to vancomycin," says Arias, the founder and scientific director of the Molecular Genetics and Antimicrobial Resistance Unit at Universidad El Bosque in Bogota, Colombia.
The VRSA isolate in this case was also resistant to teicoplanin, erythromycin, clindamycin, ciprofloxacin, gentamicin, and trimethoprimsulfamethoxazole. Beset with other infections, including carbapenem-resistant Acinetobacter baumannii, the Brazilian patient died in November 2012. The patient died while receiving meropenem, linezolid, polymyxin B sulfate, and amphotericin B.
Reference
1. Rossi F, Diaz L, Wollam A, et al. Transferable vancomycin resistance in a community-associated MRSA lineage. N Engl J Med 370;16:1524-1531
