VRSA in Philadelphia

The first U.S. case of vancomycin-resistant Staphylococcus aureus (VRSA) since 2007 has been identified in a University of Pennsylvania hospital, according to a Philadelphia Inquirer article published today. VRSA is an even more formidable but rare cousin of MRSA, an infection that kills over 19,000 people in the U.S. every year.

The most recent case is a woman on kidney dialysis who was infected both with MRSA and with vancomycin-resistant enterococci (VRE). Vancomycin is used to prevent infection in kidney patients, exposing them to resistance risks. In this case, MRSA bacteria acquired resistance to vancomycin, the drug commonly used to treat MRSA, through genetic transfer from VRE bacteria.

VRSA infections are worrisome because vancomycin is often used as a drug of last resort when other antibiotics fail. Although VRSA is still susceptible to a limited number of antibiotics, these treatments are more costly and invasive than vancomycin and can have serious side effects. Like MRSA, VRSA can be transferred between individuals directly or through objects that have come into contact with infected patients, making it a potentially dangerous force in healthcare settings.

Tracing the Roots of MRSA

A study published earlier this year used genomic analysis to trace one of the most common strains of MRSA, ST239, back to the introduction of widespread antibiotic usage in 1960's Europe. The genomic data also gave researchers insight into the transmission of MRSA on both local and global levels.

Led by Dr. Simon Harris of the Wellcome Trust Sanger Institute, the authors analyzed 63 ST239 isolates, 43 of those from different locations around the globe over a period from 1982-2003. By determining the presence single nucleotide polymorphisms (SNPs), small variable regions in an organism's genome, in each isolate, they were able to create a phylogeny that maps out the likely origin of each strain (see image).


The completed puzzle told the researchers that the isolates clustered by location, as would be expected, but that some isolates seemed to have been transmitted between two locations, perhaps by a single individual. For example, isolates from a MRSA outbreak in a London hospital were part of the same genetic cluster that belonged to Thai isolates, indicating the likelihood of a "single intercontinental transmission event."

The phylogeny was created to limit the number of common SNPs that would have come about by convergent evolution - when a mutation develops multiple times in different branches of a genetic tree. Of the SNPs that did indicate convergent evolution, over 25 percent of these were genes involved with resistance to currently-used antibiotics, showing that clinical practice of drug use is a major driver of evolution towards resistant bacteria.

Finally, the analysis allowed the researchers to calculate the rate of mutation of ST239 bacteria at one core SNP every six weeks. Using this figure, they were able to trace a common ancestor for all of the isolates to one strain originating in Europe in the mid-to-late 1960's. This coincides with the beginning of the popular use of antibiotics in Europe, and with the first identified MRSA cases there.

This study may be most useful for the technique it uses to trace resistant isolates through time and location. Combined with improved global surveillance of MRSA, these methods may be used to detect introduction of new strains and target the needed forms of diagnostics and interventions, the authors write.

Coauthor Dr. Sharon Peacock told The Telegraph:

"We are now able to discriminate between one strain and another, even where they are very closely related. Our research should inform global surveillance strategies to track the spread of MRSA.

"The implications for public health are clear: this technology represents the potential to trace transmission pathways of MRSA more definitively so that interventions or treatments can be targeted with precision and according to need."

Bedside Reading

Maryn McKenna is the author of a new book released yesterday, "Superbug: The Fatal Menace of MRSA," on the hospital, community, and environmental dangers of methicillin-resistant Staphylococcus aureus. McKenna, a science and medical journalist with the University of Minnesota's Center for Infectious Disease Research and Policy, discussed the book yesterday on NPR's Fresh Air with Terry Gross. You can listen to the interview here or read the transcript online.

In the interview, McKenna discusses the increased complication in treating MRSA infections due to crossover between what were originally separate healthcare-associated and community-associated MRSA strains. Now, she says, strains that were typically isolated to the hospital or to community settings (prisons and locker rooms, for example) are showing up in unexpected places and behaving in unexpected ways. As a result, doctors are not sure what the drug-resistance pattern of a given infection is -- and as a result, rely on prescribing the most intense drugs available. She also explains the dangers of low-dose antibiotics in farm animals, and the possibility of MRSA being transferred from animals to humans. Although she acknowledges that preventing the spread of MRSA and the development of resistance in general is difficult given the overprescription and overuse of antibiotics, as well as MRSA's resilience as an organism, McKenna does recommend a few things people can do to protect themselves: wash your hands, make sure your kids shower after sports, and use antibiotics appropriately.

Image courtesy of www.npr.org

More on CDIs

If there is a pathogenic face to antibiotic resistance, it's MRSA, or methicillin-resistant Staphylococcus aureus. It can be gross and gory, affects both the elderly in nursing homes and children on athletic teams, and causes more deaths in the U.S. each year than AIDS. But is it the infection you should be most worried about during a hospital stay?

New research suggests that Clostridium difficile infections (CDIs) may be overtaking MRSA as the most threatening of the antibiotic-resistant infections the American healthcare system faces. Scientists affiliated with Duke's Infection Control Outreach Network (DICON) presented a study at last weekend's Fifth Decennial International Conference on Healthcare- Associated Infections that found CDI rates in excess of MRSA infections in community hospitals in the Southeast United States. In this group of 30 hospitals, which were monitored from January 2008 through June 2009, C. difficle was the leading healthcare-associated infection (HAI). C. difficile beat out MRSA, 612 cases (0.26 per 1,000 patient-days) to 505 cases (0.22 per 1,000 patient-days).

Previous studies also suggest that the mortality rate for CDI is higher than MRSA. But it's also possible that CDI is more preventable, because it is so closely linked to previous antibiotic usage in each individual patient, and largely confined to healthcare settings (except in pediatrics - see "CDIs Increasing in Children" below). This is one case where effective infection control and prevention strategies, as well as public education, could go a long way. You can learn more about C. difficile from the CDC and the Mayo Clinic.

Antibiotic Resistance 101

Antibiotic resistance is an inevitable result of the use of antibiotics, and is not a new concept. Even in the 1940’s, when penicillin was first mass-produced, resistant bacteria were recognized. But misuse and overuse of antibiotics both create added pressure for the development and spread of resistant bacteria, resulting in reservoirs of resistance that threaten treatment success in all regions of the world.

Acquired antibiotic resistance is the result of a genetic mutation that changes the way a microbe responds to a drug made to eradicate it. These responses vary greatly – for example, some genetically resistant bacteria have altered binding sites so that prevent antibiotic molecules from attaching to cell walls, others have mechanisms to pump out antibiotics when they do get inside.

Even before an antibiotic is administered, a portion of a bacterial population may be genetically resistant to that antibiotic. But adding a drug to the mix puts selective pressure on the community, killing those bacteria that are susceptible but allowing resistant bacteria to survive and multiply. This is especially a risk when antibiotics are administered at low doses not strong enough to wipe out whole populations, or when antibiotic therapy is initiated but then terminated before it can run its full course of wiping out an infection. This leaves lingering populations of bacteria that have been exposed to the drug and given the opportunity to develop resistance. Without susceptible bacteria to compete with, antibiotic-resistant bacteria can quickly multiply and develop into an infection that is no longer treatable by the usual drugs, requiring more aggressive treatment or sometimes leaving doctors with no options – especially in developing nations, where drug access is often limited.

Diagram credit: http://microvet.arizona.edu/Courses/MIC438/decker/
AntibioticRes/AntibioticResistance.html

Genes conferring antibiotic resistance can also propagate in commensal (non-disease causing) bacteria, which are native to all humans, and then be transferred to pathogenic bacteria through conjugation. Both commensal and pathogenic resistant bacteria can be spread through the food supply (e.g. Escherichia coli), or between humans in clincal or community settings (e.g. methicillin-resistant Staphylococcus aureus, or MRSA). These resistant strains are an increasing medical and economic concern - MRSA alone kills 19,000 Americans every year, and one recent study found that antibiotic-resistant infections cost the U.S. healthcare system more than $20 billion annually. The CDC and WHO both rank antibiotic resistance as one of the top three public health concerns worldwide.