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Clinical Laboratories and Pathology Groups

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Clinical Laboratories and Pathology Groups

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Wellcome Sanger Institute Study Discovers New Strain of C. Difficile That Targets Sugar in Hospital Foods and Resists Standard Disinfectants

Researchers believe new findings about genetic changes in C. difficile are a sign that it is becoming more difficult to eradicate

Hospital infection control teams, microbiologists, and clinical laboratory professionals soon may be battling a strain of Clostridium difficile (C. difficile) that is even more resistant to disinfectants and other forms of infection control.

That’s the opinion of research scientists at the Wellcome Sanger Institute (WSI) and the London School of Hygiene and Tropical Medicine (LSHTM) in the United Kingdom who discovered the “genetic changes” in C. difficile. Their genomics study, published in Nature Genetics, shows that the battle against super-bugs could be heating up.

A WSI news release states the researchers “identified genetic changes in the newly-emerging species that allow it to thrive on the Western sugar-rich diet, evade common hospital disinfectants, and spread easily.”

Microbiologists and infectious disease doctors know full well that this means the battle to control HAIs is far from won.

C. difficile is currently forming a new species with one group specialized to spread in hospital environments. This emerging species has existed for thousands of years, but this is the first time anyone has studied C. difficile genomics in this way to identify it. This particular [bacterium] was primed to take advantage of modern healthcare practices and human diets,” said Nitin Kumar, PhD (above), in the news release. (Photo copyright: Wellcome Sanger Institute.) 

Genomic Study Finds New Species of Bacteria Thrive in Western Hospitals

In the published paper, Nitin Kumar, PhD, Senior Bioinformatician at the Wellcome Sanger Institute and Joint First Author of the study, described a need to better understand the formation of the new bacterial species. To do so, the researchers first collected and cultured 906 strains of C. difficile from humans, animals, and the environment. Next, they sequenced each DNA strain. Then, they compared and analyzed all genomes.

The researchers found that “about 70% of the strain collected specifically from hospital patients shared many notable characteristics,” the New York Post (NYPost) reported.

Hospital medical laboratory leaders will be intrigued by the researchers’ conclusion that C. difficile is dividing into two separate species. The new type—dubbed C. difficile clade A—seems to be targeting sugar-laden foods common in Western diets and easily spreads in hospital environments, the study notes. 

“It’s not uncommon for bacteria to evolve, but this time we actually see what factors are responsible for the evolution,” Kumar told Live Science.

New C. Difficile Loves Sugar, Spreads

Researchers found changes in the DNA and ability of the C. difficile clade A to metabolize simple sugars. Common hospital fare, such as “the pudding cups and instant mashed potatoes that define hospital dining are prime targets for these strains”, the NYPost explained.

Indeed, C. difficile clade A does have a sweet tooth. It was associated with infection in mice that were put on a sugary “Western” diet, according to the Daily Mail, which reported the researchers found that “tougher” spores enabled the bacteria to fight disinfectants and were, therefore, likely to spread in healthcare environments and among patients.

“The new C. difficile produces spores that are more resistant and have increased sporulation and host colonization capacity when glucose or fructose is available for metabolism. Thus, we report the formation of an emerging C. difficile species, selected for metabolizing simple dietary sugars and producing high levels or resistant spores, that is adapted for healthcare-mediated transmission,” the researchers wrote in Nature Genetics.

Bacteria Pose Risk to Patients

The findings about the new strains of C. difficile bacteria now taking hold in provider settings are important because hospitalized patients are among those likely to develop life-threatening diarrhea due to infection. In particular, people being treated with antibiotics are vulnerable to hospital-acquired infections, because the drugs eliminate normal gut bacteria that control the spread of C. difficile bacteria, the researchers explained.

According to the Centers for Disease Control and Prevention (CDC), C. difficile causes about a half-million infections in patients annually and 15,000 of those infections lead to deaths in the US each year.

New Hospital Foods and Disinfectants Needed

The WSI/LSHTM study suggests hospital representatives should serve low-sugar diets to patients and purchase stronger disinfectants. 

“We show that strains of C. difficile bacteria have continued to evolve in response to modern diets and healthcare systems and reveal that focusing on diet and looking for new disinfectants could help in the fight against this bacteria,” said Trevor Lawley, PhD, Senior Author and Group Leader of the Lawley Lab at the Wellcome Sanger Institute, in the news release.

Microbiologists, infectious disease physicians, and their associates in nutrition and environmental services can help by understanding and watching development of the new C. difficile species and offering possible therapies and approaches toward prevention.

Meanwhile, clinical laboratories and microbiology labs will want to keep up with research into these new forms of C. difficile, so that they can identify the strains of this bacteria that are more resistant to disinfectants and other infection control methods.  

—Donna Marie Pocius

Related Information:

Adaptation of Host Transmission Cycle During Clostridium Difficile Speciation

Diarrhea-causing Bacteria Adapted to Spread in Hospitals

Sugary Western Diets Fuel Newly Evolving Superbug

New Carb-Loving Superbug is Primed to Target Hospital Food

Superbug C Difficile Evolving to Spread in Hospitals and Feeds on the Sugar-Rich Western Diet

CDC: Healthcare-Associated Infections-C. Difficile  

Lurking Below: NIH Study Reveals Surprising New Source of Antibiotic Resistance That Will Interest Microbiologists and Medical Laboratory Scientists

Genomic analysis of pipes and sewers leading from the National Institutes of Health Clinical Care Center in Bethesda, Md., reveals the presence of carbapenem-resistant organisms; raises concern about the presence of multi-drug-resistant bacteria previously undetected in hospital settings

If hospitals and medical laboratories are battlegrounds, then microbiologists and clinical laboratory professionals are frontline soldiers in the ongoing fight against hospital-acquired infections (HAIs) and antibiotic resistance. These warriors, armed with advanced testing and diagnostic skills, bring expertise to antimicrobial stewardship programs that help block the spread of infectious disease. In this war, however, microbiologists and medical laboratory scientists (AKA, medical technologists) also often discover and identify new and potential strains of antibiotic resistance.

One such discovery involves a study published in mBio, a journal of the American Society for Microbiology (ASM), conducted by microbiologist Karen Frank, MD, PhD, D(AMBB), Chief of the Microbiology Service Department at the National Institutes of Health (NIH), and past-president of the Academy of Clinical Laboratory Physicians and Scientists (ACLPS). She and her colleagues identified a surprising source of carbapenem-resistant organisms—the plumbing, sewers, and wastewater beneath the National Institutes of Health Center (NIHCC) in Bethesda, Md. And they theorize similar “reservoirs” could exist beneath other healthcare centers as well.

Potential Source of Superbugs and Hospital-Acquired Infections

According to the mBio study, “Carbapenemase-producing organisms (CPOs) are a global concern because of the morbidity and mortality associated with these resistant Gram-negative bacteria. Horizontal plasmid transfer spreads the resistance mechanism to new bacteria, and understanding the plasmid ecology of the hospital environment can assist in the design of control strategies to prevent nosocomial infections.”

Karen Frank, MD, PhD

Karen Frank, MD, PhD (above), is Chief of the Microbiology Service Department at the National Institutes of Health and past-president of the Academy of Clinical Laboratory Physicians and Scientists. She suggests hospitals begin tracking the spread of the bacteria. “In the big picture, the concern is the spread of these resistant organisms worldwide, and some regions of the world are not tracking the spread of the hospital isolates.” (Photo copyright: National Institutes of Health.)

Frank’s team used Illumina’s MiSeq next-generation sequencer and single-molecule real-time (SMRT) sequencing paired with genome libraries, genomics viewers, and software to analyze the genomic DNA of more than 700 samples from the plumbing and sewers. They discovered a “potential environmental reservoir of mobile elements that may contribute to the spread of resistance genes, and increase the risk of antibiotic resistant ‘superbugs’ and difficult to treat hospital-acquired infections (HAIs).”

Genomic Sequencing Identifies Silent Threat Lurking in Sewers

Frank’s study was motivated by a 2011 outbreak of antibiotic-resistant Klebsiella pneumoniae bacteria that spread through the NIHCC via plumbing in ICU, ultimately resulting in the deaths of 11 patients. Although the hospital, like many others, had dedicated teams working to reduce environmental spread of infectious materials, overlooked sinks and pipes were eventually determined to be a disease vector.

In an NBC News report on Frank’s study, Amy Mathers, MD, Director of The Sink Lab at the University of Virginia, noted that sinks are often a locus of infection. In a study published in Applied and Environmental Microbiology, another journal of the ASM, Mathers noted that bacteria in drains form a difficult to clean biofilm that spreads to neighboring sinks through pipes. Mathers told NBC News that despite cleaning, “bacteria stayed adherent to the wall of the pipe” and even “splashed out” into the rooms with sink use.

During the 2011-2012 outbreak, David Henderson, MD, Deputy Director for Clinical Care at the NIHCC, told the LA Times of the increased need for surveillance, and predicted that clinical laboratory methods like genome sequencing “will become a critical tool for epidemiology in the future.”

Frank’s research fulfilled Henderson’s prediction and proved the importance of genomic sequencing and analysis in tracking new potential sources of infection. Frank’s team used the latest tools in genomic sequencing to identify and profile microbes found in locations ranging from internal plumbing and floor drains to sink traps and even external manhole covers outside the hospital proper. It is through that analysis that they identified the vast collection of CPOs thriving in hospital wastewater.

In an article, GenomeWeb quoted Frank’s study, noting that “Over two dozen carbapenemase gene-containing plasmids were identified in the samples considered” and CPOs turned up in nearly all 700 surveillance samples, including “all seven of the wastewater samples taken from the hospital’s intensive care unit pipes.” Although the hospital environment, including “high-touch surfaces,” remained free of similar CPOs, Frank’s team noted potential associations between patient and environmental isolates. GenomeWeb noted Frank’s findings that CPO levels were in “contrast to the low positivity rate in both the patient population and the patient-accessible environment” at NIHCC, but still held the potential for transmission to vulnerable patients.

Antibiotic-Resistance: A Global Concern

The Centers for Disease Control and Prevention (CDC) reports that more than two million illnesses and 23,000 deaths in the US are caused each year by antibiotic resistance, with 14,000 deaths alone linked to antibiotic resistance associated with Clostridium difficile infections (CDI). Worldwide those numbers are even higher.

Second only to CDI on the CDC’s categorized list of “18 drug-resistant threats to the United States” are carbapenem-resistant Enterobacteriaceae (CRE).

Since carbapenems are a “last resort” antibiotic for bacteria resistant to other antibiotics, the NIHCC “reservoir” of CPOs is a frightening discovery for physicians, clinical laboratory professionals, and the patients they serve.

The high CPO environment in NIHCC wastewater has the capability to spread resistance to bacteria even without the formal introduction of antibiotics. In an interview with Healthcare Finance News, Frank indicated that lateral gene transfer via plasmids was not only possible, but likely.

“The bacteria fight with each other and plasmids can carry genes that help them survive. As part of a complex bacterial community, they can transfer the plasmids carrying resistance genes to each other,” she noted. “That lateral gene transfer means bacteria can gain resistance, even without exposure to the antibiotics.”

The discovery of this new potential “reservoir” of CPOs may mean new focused genomic work for microbiologists and clinical laboratories. The knowledge gained by the discovery of CPOs in hospital waste water and sinks offers a new target for study and research that, as Frank concludes, will “benefit healthcare facilities worldwide” and “broaden our understanding of antimicrobial resistance genes in multi-drug resistant (MDR) bacteria in the environment and hospital settings.”

Amanda Warren

Related Information:

Genomic Analysis of Hospital Plumbing Reveals Diverse Reservoir of Bacterial Plasmids Conferring Carbapenem Resistance

Snooping Around in Hospital Pipes, Scientists Find DNA That Fuels the Spread of Superbugs

CSI Bethesda: Sleuths Used Sequenced Genome to Track Down Killer

Antibiotic/Antimicrobial Resistance

Study Tracks How Superbugs Splash Out of Hospital Sink Drains

CDC: Biggest Threats

Antimicrobial Stewardship: How the Microbiology Laboratory Can Right the Ship

Superbugs Breeding in Hospital Plumbing Put Patients at Risk

Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways

Researchers at Auburn University Collaborate with Clinical Laboratory Team at Keesler Air Force Base to Detect Antibiotic-resistant Bacteria in Just 10 Minutes

This technology could provide medical labs a quick, cost-effective way to diagnose methicillin-resistant Staphylococcus aureus

Even as in vitro diagnostics manufacturers are bringing rapid molecular tests to market that can identify infectious diseases within hours, a research collaboration involving a major university and a medical laboratory at an air force base has demonstrated the ability to identify antibiotic-resistant strains of Staphylococcus in just minutes.

This innovative research is being done by Auburn University’s College of Veterinary Medicine and clinical laboratory professionals at Keesler Air Force Base. Funding is by the U.S. Air Force. This research was of particular interest to the military because the risk for Staph infection increases when individuals are subjected to unhygienic conditions in close quarters. (more…)

FDA Clears New Rapid Clinical Laboratory Test for Market that Reduces Time-to-Answer for Bloodstream Infections to Two Hours

Nanosphere’s Gram-Positive Blood Culture Nucleic Acid Test (BC-GP) gives pathologists and clinical laboratory managers a new tool in the diagnosis of septicemia

One of the more challenging diseases to diagnose and treat is septicemia. Traditional microbiology methods typically require two or three days before an accurate diagnosis can be made. Now there is news of a rapid test for bloodstream infections that can allow a hospital clinical laboratory to deliver an answer to physicians in as little as two hours.

It was just last week when the Food and Drug Administration LINK (FDA) granted a de novo petition to allow Nanosphere, Inc., of Northbrook, Illinois, to market its Gram Positive Blood Culture Nucleic Acid Test (BC-GP). This assay is design to be run on Nanosphere’s Verigene automated system. Because the time-to-answer is as little as two hours, this diagnostic technology has the potential to trigger swift changes in the current standard of care for diagnosing and treating blood infections.
(more…)

New Disinfection Technique for Hospital Rooms Will Be Useful to Clinical Pathology Laboratories

Vapor-based fumigant system could prove useful in disinfecting microbiology labs, clinical labs, and histology labs

There’s a new technology that bears great promise for improving existing methods of disinfecting hospital rooms and health facilities, including clinical laboratories. This pioneering work was developed as part of a collaboration involving infection control expert Dick Zoutman, M.D., FRCPC, who is affiliated with Queen’s University of Kingston, Ontario, Canada.

This technology is a vapor-based fumigant system and is coming to market with the name AsepticSure. It will be sold by Medizone International, Inc.. The invention makes a strong argument for changing the way hospital rooms and other healthcare facilities are disinfected. (more…)

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