The UE study sheds light on the types of bacteria in
wastewater that goes down hospital pipes to sewage treatment plants. The study
also revealed that not all infectious agents are killed after passing through
waste treatment plants. Some bacteria with antimicrobial (or antibiotic)
resistance survive to enter local food sources.
The scientists concluded that the amount of AMR genes found
in hospital wastewater was linked to patients’ length-of-stays and consumption
of antimicrobial resistant bacteria while in the hospital.
In a paper the University of Edinburgh published on medRxiv, the researchers wrote: “There was a higher abundance of antimicrobial-resistance genes in the hospital wastewater samples when compared to Seafield community sewage works … Sewage treatment does not completely eradicate antimicrobial-resistance genes and thus antimicrobial-resistance genes can enter the food chain through water and the use of [processed] sewage sludge in agriculture. As hospital wastewater contains inpatient bodily waste, we hypothesized that it could be used as a representation of inpatient community carriage of antimicrobial resistance and as such may be a useful surveillance tool.”
Additionally, they wrote, “Using metagenomics to identify
the full range of AMR genes in hospital wastewater could represent a useful
surveillance tool to monitor hospital AMR gene outflow and guide environmental
policy on AMR.”
Antimicrobial stewardship programs are becoming increasingly critical to preventing the spread of AMR bacteria. “By having those programs, [there are] documented cases of decreased antibiotic resistance within organisms causing these infections,” Paul Fey, PhD, of the University of Nebraska Medical Center, told MedPage Today. “This is another indicator of how all hospitals need to implement stewardship programs to have a good handle on decreasing antibiotic use.” [Photo copyright: University of Nebraska.]
Don’t Waste the Wastewater
Antibiotic resistance occurs when bacteria change in response to medications to prevent and treat bacterial infections, according to a World Health Organization (WHO) fact sheet. The CDC estimates that more than 23,000 people die annually from two million antibiotic-resistance infections.
Wastewater, the UE scientists suggest, should not go to
waste. It could be leveraged to improve hospitals’ detection of patients with antimicrobial
resistance, as well as to boost environment antimicrobial-resistance polices.
They used metagenomics (the study of genetic material
relative to environmental samples) to compare the antimicrobial-resistance
genes in hospital wastewater against wastewater from community sewage
points.
The UE researchers:
First collected samples over a 24-hour period from various areas in a tertiary hospital;
They then obtained community sewage samples from various locations around Seafield, Scotland;
Antimicrobial-resistance genes increased with longer length of patient stays, which “likely reflects transmission amongst hospital inpatients,” researchers noted.
Fey suggests that further research into using sequencing
technology to monitor patients is warranted.
“I think that monitoring each patient and sequencing their
bowel flora is more likely where we’ll be able to see if there’s a significant
carriage of antibiotic-resistant organisms,” Fey told MedPage Today. “In
five years or so, sequencing could become so cheap that we could monitor every
patient like that.”
Fey was not involved in the University of Edinburgh
research.
Given the rate at which AMR bacteria spreads, finding antibiotic-resistance
genes in hospital wastewater may not be all that surprising. Still, the University
of Edinburgh study could lead to cost-effective ways to test the genes of
bacteria, which then could enable researchers to explore different sources of
infection and determine how bacteria move through the environment.
And, perhaps most important, the study suggests clinical
laboratories have many opportunities to help eliminate infections and slow
antibiotic resistance. Microbiologists can help move their organizations forward
too, along with infection control colleagues.
Contrary to CMS and Joint Commission programs implemented in 2017 to reduce them, incidents of hospital-acquired infections have risen for the past few years
Nevertheless, a recent Leapfrog Group report indicates hospitals are finding it increasingly difficult to remove infections all together. This has many healthcare leaders concerned.
The report, which was analyzed by Castlight Health, states that the number of hospitals reporting zero infections has declined significantly since 2015, according to a news release. According to the Leapfrog Group’s report:
Two million people acquire HAIs every year;
90,000 people die annually from HAIs;
HAI costs range from $1,000 to $50,000 depending on the infection.
Hospitals spend $28 to $45 billion annually on HAI costs, Healthcare Finance reported.
“I think it’s far too easy to let something slip, so it’s clear that there really needs to be a renewed focus on getting back to zero. We do still see some hospitals that are getting to zero, so it’s clearly possible,” Erica Mobley (above), Leapfrog Group’s Director of Operations, told Fierce Healthcare. (Photo copyright: LinkedIn.)
Regressing Instead of Progressing Toward Total HAI Elimination
Leapfrog Group’s report is based on 2017 hospital survey data submitted by 2,000 providers. The data indicates that in just two years the number of hospitals reporting zero HAIs dropped by up to 50%. The reported HAIs include:
Central line-associated bloodstream infections (CLABSI) occurring in Intensive Care and other units: 12.7% of hospitals reporting zero CLABSI infections in 2017, down from 25% in 2015;
The remaining infection measures studied by Leapfrog Group had less dramatic decreases over the same time period, according to Fierce Healthcare. Nevertheless, they are significant. They include:
Surgical site infections (SSI) following colon surgery: 19% zero infections compared to 23% previously;
Clostridium difficile (C. difficile) inpatient infections: 3% zero inpatient infections in 2017, compared to 5% in 2015.
Joint Commission Studies Antimicrobial Program Progress
Hospitals have revised their antimicrobial programs, which originally operated on a “top-down” structure, to programs that include clinicians from throughout entire provider organizations;
Health information technology (HIT) can enable real-time opportunities to launch antimicrobial therapy and treat patients; and,
Some barriers exist in getting resources to integrate technology and analyze data.
“These programs used expansion of personnel to amplify the antimicrobial stewardship programs’ impact and integrated IT resources into daily workflow to improve efficiency,” the researchers wrote. “Hospital antimicrobial stewardship programs can reduce inappropriate antimicrobial use, length of stay, C. difficile infection, rates of resistant infections, and cost.”
What Do CMS and Joint Commission Expect?
According to Contagion, while the Joint Commission program is part of medication management, CMS places its requirements for the antimicrobial stewardship program under “infection prevention.”
CMS requirements for an antimicrobial stewardship program include:
Developing antimicrobial stewardship program policies and procedures;
Implementing hospital-wide efforts;
Involving antimicrobial stakeholders for focus on antimicrobial use and bacterial resistance;
Setting evidence-based antimicrobial use goals; and,
Reducing effects of antimicrobial use in areas of C. difficile infections and antibiotic resistance.
Leapfrog Group’s data about fewer hospitals reporting zero infections offers opportunities for hospital laboratory microbiology professionals to get involved with hospital-wide antimicrobial program teams and processes and help their hospitals progress back to zero HAIs. Clinical laboratories, both hospital-based and independent, also have opportunities to contribute to improving the antimicrobial stewardship efforts of the physicians who refer them specimens.
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.
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 (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.
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.”
Is gut microbiota the fabled fountain of youth? Researchers at Valenzano Research Lab in Germany found it works for killifish. Could it work for other vertebrates as well?
Research into the microbiomes of humans and other animals is uncovering tantalizing insights as to how different microbes can be beneficial or destructive to the host. It is reasonable to expect ongoing research will eventually give microbiologists and clinical laboratories useful new medical laboratory tests that assess an individual’s microbiome for diagnostic and therapeutic purposes.
Human microbiota (AKA, microbiome) have been identified as having a key role in several different health conditions. In previous ebriefings, Dark Daily reported on several breakthroughs involving the microbiome that bring the promise of precision medicine ever closer. Research and clinical studies are contributing to more accurate diagnoses, identification of best drugs for specific patients, and, enhanced information for physician decision-making, to name just a few benefits.
Valenzano Lab published its study online in August. The team of scientists and researchers led by Dario Valenzano, PhD, focused on the longevity of the turquoise killifish (Nothobranchius furzeri), a tiny fish native to the African countries of Mozambique and Zimbabwe. They found that when older killifish ate the fecal matter of younger killifish they lived longer. The fecal matter carried the microbiota to the older fish and extended their lifespans.
Moving Microbiome from One Gut to Another
To perform the research, Valenzano and his team first treated killifish that were nine and a half weeks old (considered middle-aged) with antibiotics to cleanse their gut flora. The fish were then placed in a sterile aquarium containing the gut contents of young adult killifish that were just six weeks old. Although killifish won’t typically eat feces, they would nip at the gut contents in the water and swallow some of the microbes from the younger fish in the process. The researchers discovered that the transplanted microbes were able to successfully colonize the stomachs of the older fish.
Dario Valenzano, PhD (above), gazes at an older Killifish, the subject in his research into increased aging at the Valenzano Research Lab in Cologne, Germany. Studies of the microbiomes of different species is expected to eventually give microbiologists new and useful clinical laboratory tests. (Photo copyright: Max Planck Institute for Biology of Aging.)
When the middle-aged killifish reached the age of 16 weeks—considered elderly—their gut microbiomes were still similar to that of a six-week-old fish. The process had a noticeable effect on the lifespan of the killifish that received the microbiome transplants from the young fish. They lived 41% longer than killifish that received microbes from middle-aged fish and their longevity increased by 37% over fish that were not exposed to any treatment at all. In addition, at 16 weeks, the killifish who had received the transplants were much more active than fish of the same age who had not received the transplants.
“These results suggest that controlling the composition of the gut microbes can improve health and increase life span,” the study paper noted. “The model system used in this study could provide new ways to manipulate the gut microbial community and gain key insights into how the gut microbes affect aging. Manipulating gut microbes to resemble a community found in young individuals could be a strategy to delay the onset of age-related diseases.”
Transferring Fecal Microbiota to Save/Extend Human Lives
Previous research has indicated there may be a connection between microbiomes and aging in some animals, and that the diversity of gut microbes decreases with age. This study proved that this same pattern is true in turquoise killifish.
However, Valenzano does not know how the microbes are affecting the lifespans of the older killifish. “It is possible that an aging immune system is less effective at protecting the micro-organisms in the intestines, with the result that there is a higher prevalence of pathogens in older guts. The gut microbiota in a young organism could help to counter this and therefore support the immune system and prevent inflammation. This could lead to longer life expectancy and better health,” he stated in a press release.
“You can really tell whether a fish is young or old based on its gut microbiota,” Valenzano told Nature. He noted, however, that it is too early to determine if fecal transplants can be used in humans to extend life. “I wouldn’t go that far. This is really early evidence that this has a potential positive effect.”
There is, however, a similar procedure used in humans called Fecal Microbiota Transplant or FMT that has demonstrated promising results in treating certain illnesses.
In a fecal transplant, fecal matter is collected from an approved donor, treated, and placed in a patient during a colonoscopy, endoscopy, sigmoidoscopy, or enema. The purpose of the transplant is to replace good bacteria in a colon that has undergone an event that caused the colon to be inundated with bad bacteria, such as Clostridium difficile, resulting in C. diff. infection, a life-threatening illness that, according to the Centers for Disease Control and Prevention (CDC), kills tens of thousands of people each year.
“The challenge with all of these experiments is going to be to dissect the mechanism. I expect it will be very complex,” stated Heinrich Jasper, PhD, in the Nature article. Jasper is a professor at the Buck Institute for Research on Aging in Novato, California. His lab is working on similar research with microbiome transplants in fruit flies. He predicts this type of longevity research will be performed on other animals in the future.
Valenzano’s and Jasper’s research may eventually create new diagnostic tools for microbiologists to assess the microbiome of individual patients. This technology may also enable microbiologists to advise pathologists and clinical laboratories regarding what specific microbes may be harmful and what microbes may be therapeutically beneficial to patients.
As science learns more about the human genome, new companies are being formed to offer consumers at-home microbiology test kits, a development many microbiologists consider worrisome
Can consumers rely on the accuracy of at-home microbiology tests that promise to give them useful information about their microbiome? That’s just one question being asked by clinical laboratory scientists and microbiologists in response to the proliferation of companies offering such tests.
Advances in gene sequencing technology, new insights into the human microbiome, and more sophisticated software to analyze test data are fueling the growth of companies that want to offer consumers at-home microbiology test kits. And no less an authority than the American Academy of Microbiology (ASM) states in a 2017 report, that knowledge of the microbiome can revolutionize healthcare as “insights acquired from NGS [next-generation sequencing] methods can be exploited to improve our health as individuals and the greater public health.”
The move towards more “precision medicine” in terms of diagnostics and treatments, according to the ASM, is based in part on microbial genomic testing, which when combined with a patient’s medical history, clinical signs, symptoms, and human genomic information, can help “create treatment pathways that are individualized and tailored for each patient.”
However, critics worry about overreach given current limitations in the analysis and diagnosis of microbiome data produced by testing, particularly in connection to the rising number of consumer self-testing services aimed at the general public.
No Science to Back Up Claims of Accuracy for At-Home Microbiology Tests
A recent article from the MIT Technology Review, notes that these at-home microbiology testing services, while exciting, can only offer limited information—despite claims. Companies such as Thryve, for example, offer visitors to their website a $99 gut health kit, which they recommend using four times per year. The goal is to use the data to target regimens of supplements and “correct” problems the testing identifies.
Another company, uBiome, offers physician-ordered and customer-requested test kits that the company suggests can determine risk factors for disease. However, critics suggest science cannot currently back up those claims. Concerns about the value of such consumer self-testing, the legitimacy of recommendations based on “diagnoses,” and basic health privacy are leading to serious concerns within the scientific community.
Ethics and Realistic Expectations
One additional criticism of consumer self-testing of microbiomes involves privacy. An NPR article on the American Gut Project (AGP), which Dark Daily reported on in previous e-briefings, notes that those tested may be disclosing quite a bit of information about themselves. The article’s author points out basic privacy and value concerns about the AGP. American Gut Project is a crowd-funded “citizen science project,” and part of the larger global Earth Microbiome Project, described as a “massively collaborative effort to characterize microbial life on this planet.” (See Dark Daily, “Get the Poop on Organisms Living in Your Gut with a New Consumer Laboratory Test Offered by American Gut and uBiome,” September 9, 2015.)
One example of an at-home microbiology test marketed to consumers is the SmartGut by uBiome (above). It is “a microbiome screening test that uses precision sequencing technology to identify key microorganisms in your gut, both pathogenic and commensal.” (Photo copyright: uBiome.)
In her blog post on the Center for Microbiome Informatics and Therapeutics’ website, Tami Lieberman, PhD, claims that “microbiome profiling is messy (and I’m not just talking about the sample collection).” Lieberman submitted samples to American Gut and uBiome for her article. Lieberman’s skepticism of the services is based on two things:
1. There is no “gold standard” for microbiome DNA profiling technology or analysis methods at this time; and,
2. Human microbiomes are in her words, “a moving target, changing with age and diet.”
Thus, the best these services can provide, Lieberman argues, is a snapshot of gut microbes at one period of time. Additionally, she claims there is a danger in trying to interpret personal microbiome data. And, Lieberman is not alone in her criticism.
Science Must Be ‘On Guard’ Against Hype about the Usefulness of Microbiome Tests
Martin Blaser, MD, PhD, Director of the Human Microbiome Project at New York University, also criticizes at-home self-tests of microbiomes. In a New York Times article, Blaser points out that the enormous amount of data generated by microbiome testing is “basically uninterpretable” at this time. According to Blaser, scientists can chart the presence, absence, and levels of specific microbiomes and note correlations, but there is no way to know if changes to microbiomes in a particular patient signal disease risk, progression, or development.
The study of microbiomes is still in its nascent stages, so despite there being significant information correlating the presence or absence of specific microbes to diseases, Blaser states that scientists are currently unsure of what that correlation implies. They simply know the correlations exist.
The “gold rush” of companies offering consumers an at-home microbiology test requires skepticism, notes Hanage. He further urges researchers, press officers, and journalists to remain objective. Hanage writes, “Press officers must stop exaggerating results, and journalists must stop swallowing them whole.” Hanage warns that scientists should be on guard against the “buzz around the field” distorting scientific priorities and misleading the public at large. So, while studies of the human microbiome do carry vast potential for medical laboratories and pathologists to change healthcare and healthcare diagnostics, a healthy dose of skepticism is still the best medicine.
