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Study Suggests “Superbugs” May be More Diverse and Harder to Detect than Previously Thought

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March 6, 2017

A well-known group of "superbugs," carbapenem-resistant Enterobacteriaceae (CRE) that is very resistant to almost all antibiotics, appears to be more diverse and harder to identify than health experts had realized, according to a study published in the January 31, 2017 issue of the Proceedings of the National Academy of Sciences.

Concern over CRE has been on the rise in recent years. According to the U.S. Centers for Disease Control and Prevention (CDC), CRE cause about 9,300 infections and 600 deaths each year, and both are increasing. Recent CDC director Tom Frieden, MD, MPH, has called CRE "nightmare bacteria." (Read CRE Superbugs Rising Threat in U.S.) CRE acquire a genetic mutation that allows them to be resistant to multiple antibiotics and contain pieces of DNA (plasmids) that can transfer antibiotic resistance to other bacteria normally found in the human body.

Healthy people don't usually get CRE infections, but seriously ill patients who are more vulnerable, such as those in hospitals or nursing homes, are more likely to get infected. CRE are typically detected by culturing samples collected from patients suspected of having infections. Susceptibility testing is done on the bacteria that grow in the cultures to determine the ability of antibiotics to treat the bacteria.

The recent study of four hospitals, conducted by researchers at the Harvard T.H. Chan School of Public Health and the Broad Institute of MIT and Harvard, found information not previously known: that CRE are very diverse. Instead of one type of bacteria with one specific genetic mutation causing CRE infections within a group of patients in a healthcare facility, many types of bacteria with many different genetic mutations can cause CRE infections.

Further, some patients may be carriers; they may be transmitting CRE without becoming ill themselves. These patients are not usually tested for CRE, which makes the bacteria hard to detect and prevent in a healthcare facility.

For the study, the researchers looked at about 250 samples of CRE from hospitalized patients from three Boston hospitals and one in Irvine, California over 16 months. The team studied the genetic sequences of bacteria they isolated from the blood, urine, wounds, and respiratory tracts of patients in the four hospitals.

The researchers found little evidence of direct transmission of CRE between patients. They were able to determine this because the genetic sequences of the bacteria from patients in the same hospitals at about the same times often did not match. This also led the research team to think it's possible that some patients may be carriers of CRE.

The findings from the study show that surveillance and testing for CRE should be expanded beyond current practice, say the researchers. And more studies need to be conducted outside hospital settings and among people who may be carriers.

"While the typical focus has been on treating sick patients with CRE-related infections, our new findings suggest that CRE is spreading beyond the obvious cases of disease. We need to look harder for this unobserved transmission within our communities and health care facilities if we want to stamp it out," said William Hanage, Ph.D., an associate professor of epidemiology at Harvard Chan School and the senior author of the study, adding "[t]he best way to stop CRE making people sick is to prevent transmission in the first place."

The CDC has published a Vital Signs report on what can be done to help limit the spread of CRE and recently issued an updated guidance for control of CRE in healthcare facilities.

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Hanage, William P. et al. Multi-institute analysis of carbapenem resistance reveals remarkable diversity, unexplained mechanisms, and limited clonal outbreaks. Proceedings of the National Academy of Sciences, January 17, 2017. Available online at http://www.pnas.org/content/early/2017/01/10/1616248114.full. Accessed January 24, 2017.

(January 16, 2017) Drug-resistant 'nightmare bacteria' show worrisome ability to diversify and spread. Harvard T.H. Chan School of Public Health. Available online at https://www.hsph.harvard.edu/news/press-releases/drug-resistant-nightmare-bacteria-diversify-spread/. Accessed January 24, 2017.

(March 5, 2013) Vital Signs Telebriefing on Carbapenem-Resistant Enterobacteriaceae. Available online at https://www.cdc.gov/media/releases/2013/t0305_lethal_cre.html. Accessed January 24, 2017.

(January 16, 2017) Branswell, Helen. Dangerous superbug appears to be spreading stealthily in US hospitals. Stat. Available online at https://www.statnews.com/2017/01/16/cre-superbug/. Accessed January 24, 2017.