Fighting Nightmare Bacteria Is Like a Game of Whack-a-Mole—It Keeps Popping Up in Unexpected Places

The pathogen referred to as a "nightmare bacteria" is quietly adapting and spreading faster than anticipated.

If you are not yet familiar with carbapenem-resistant Enterobacteriaceae (CRE), it is quickly becoming a household term for severe antibiotic-resistant infections. Many people are familiar Escherichia coli, or E. coli, a type of CRE, but other members of the Enterobacteriaceae family can also become resistant. A recent study published in the Proceedings of the National Academy of Sciences looked at forms of CRE, including Klebsiella pneumoniae, which recently killed a Nevada woman.

These CREs are a serious threat to public health. While Klebsiella and Escherichia normally populate the human gut, the bacteria sometimes cause serious infection when they escape that environment, especially if they are resistant to treatments like antibacterials. According to the Centers for Disease Control and Prevention, approximately 9,300 CRE-associated infections occur each year in the US, with an estimated 600 deaths.

Currently known forms of CRE transmission include:

Direct contact with an infected person, contaminated surfaces, or feces.
In healthcare settings, surgical sites can become infected, and CRE is spread through catheters, ventilators, and other devices.
Equipment in healthcare settings, like sinks and stethoscopes, can become contaminated with CRE.

The researchers, led by scientists Gustavo Cerqueira and Ashlee Earl of the Broad Institute of Harvard and MIT, surveyed the emergence of CREs, a so-called superbug, in its most common habitat—hospitals—over a 16-month period between August 2012 and November 2013.

While CRE is usually evaluated on a case-by-case occurrence basis, this study used genome sequencing to study prevalence and diversification of CRE in 250 samples taken from patients in three different hospitals in Boston, Massachusetts, and one hospital in Irvine, California. Researchers were also able to compare their findings to CRE samples collected from the Boston hospitals between 2006 and 2012.

Fighting Nightmare Bacteria Is Like a Game of Whack-a-Mole—It Keeps Popping Up in Unexpected Places — Enterobacteriaceae cultures appear as clover-leaf shapes when resistant to carbapenems (antibiotics) in a modified Hodge test. *Image via Centers for Disease Control and Prevention*

At present, here are the latest findings on how CRE is evolving on two coasts:

The samples collected showed more diversity than expected:

While K. pneumoniae has been the most frequent cause of CRE infection in the United States, only a small number of the CRE variants identified in this study were closely related strains of K. pneumoniae.

In a press release, William Hanage, an associate professor of epidemiology at the Harvard T. H. Chan School of Public Health, and senior author on the study, noted that his team found a "riot of diversity" in species of CRE and genetic material with carbapenem resistance.

Whole-genome sequencing may be needed to identify and understand transmission:

It appears CRE is stealthily adapting in healthcare settings, and perhaps in patients unmonitored after discharge. The study notes, "This result may suggest multiple unsampled transmission chains throughout the continuum of care, consistent with recent reports of asymptomatic carriage, which we know can continue for months after discharge." In addition to the more common non-whole-genome sequence studies, the researchers suggest wider surveillance of pathogens outside hospital settings and from asymptomatic carriers.

Asymptomatic carriers are usually healthy carriers of a pathogen from which they suffer no symptoms, but which may prove deadly to those with whom they have direct contact. The most famous asymptomatic carrier in history was Mary Mallon, a carrier of Salmonella typhi, which causes typhoid fever. Though she suffered no symptoms, Typhoid Mary, as she is better known as, is thought to have been the cause of illness of more than 3,000 New Yorkers in 1907, with many deaths.

Scientists observed resistant mechanisms not seen before:

Scientists documented previously unknown genetic traits being swapped between CRE species that enable drug resistance, noting that they "found evidence for combinations of plasmid-borne resistance mechanisms that could not be recognized based on current knowledge." Suggesting CRE is adapting more readily than previously believed, there is a need for "an aggressive approach to surveillance and isolation."

In emphasizing the need to step up discovery of how CRE is being transmitted, Hanage states:

The best way to stop CRE making people sick is to prevent transmission in the first place. If it is right that we are missing a lot of transmission, then only focusing on cases of disease is like playing Whack-a-Mole; we can be sure the bacteria will pop up again somewhere else.

— William Hanage (via press release)

On a personal level, the quiet but steady advance of drug-resistant bacteria does not mean much until it impacts you, or someone you know. At a collective level, it is us against them, and it is by no means clear who comes out better in the end.