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Clinical Laboratories and Pathology Groups

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University of Edinburgh Study Finds Antimicrobial Bacteria in Hospital Wastewater in Research That Has Implications for Microbiologists

The highly infectious bacteria can survive treatment at local sewage plants and enter the food chain of surrounding populations, the study revealed

Researchers at the University of Edinburgh (UE) in Scotland found large amounts of antimicrobial-resistance (AMR) genes in hospital wastewater. These findings will be of interest to microbiologists and clinical laboratory managers, as the scientists used metagenomics to learn “how abundances of AMR genes in hospital wastewater are related to clinical activity.”

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.

Using Metagenomics to Surveille Hospital Patients

Antimicrobial resistance is creating super bacteria that are linked to increases in hospital-acquired infections (HAIs) nationwide. Dark Daily has reported many times on the growing danger of deadly antimicrobial resistant “super bugs,” which also have been found in hospital ICUs (see “Potentially Fatal Fungus Invades Hospitals and Public Is Not Informed,” August 26, 2019.)

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.”

AMR bacteria also are being spread by human touch throughout city subways, bus terminals, and mass transportation, making it difficult for the Centers for Disease Control and Prevention (CDC) to identify the source of the outbreak and track and contain it. This has led microbiologists to conduct similar studies using genetic sequencing to identify ways to track pathogens through city infrastructures and transportation systems. (See, “Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways,” December 13, 2013.)

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;
  • Finally, they complete the genetic sequencing on an Illumina HiSeq4000 System.

The researchers reported these findings:

  • 181 clinical isolates were identified in the samples of wastewater;
  • 1,047 unique bacterial genes were detected across all samples;
  • 19 genes made up more than 60% of bacteria in samples;
  • Overriding bacteria identified as Pseudomonas and Acinetobacter environmental samples (Pseudomonas fluorescens and Acinetobacter johnsonii) were most likely from hospital pipes;
  • Gut-related bacteria—Faecalibacterium, Bacteroides, Bifidobacterium, and Escherichia, were more prevalent in the hospital samples than in those from the community;
  • 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.  

—Donna Marie Pocius

Related Information:

Secrets of the Hospital Underbelly: Abundance of Antimicrobial-Resistance Genes in Hospital Wastewater Reflects Hospital Microbial Use and Inpatient Length of Stay

Antibiotic-Resistance Genes Trouble Hospital Water; Study Emphasizes Importance of Antibiotic Stewardship Programs, Expert Says

Fact Sheet: Antibiotic Resistance

United States Gathers 350 Commitments to Combat Antibiotic Resistance, Action Must Continue

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

Dark Daily E-briefings: Hospital-Acquired Infections

NIH Study Reveals Surprising New Source of Antibiotic Resistance that Will Interest Microbiologists and Medical Laboratory Scientists

Mayo Clinic Researchers Find Some Bacteria Derail Weight Loss, Suggest Analysis of Individuals’ Microbiomes; a Clinical Lab Test Could Help Millions Fight Obesity

CDC reports more than 93-million US adults are obese, and health issues related to obesity include heart disease, stroke, type 2 diabetes, and cancers

In recent years, the role of the human microbiome in weight loss or weight gain has been studied by different research groups. There is keen interest in this subject because of the high rates of obesity, and diagnostic companies know that development of a clinical laboratory test that could assess how an individual’s microbiome affects his/her weight would be a high-demand test.

This is true of a study published this year in Mayo Clinic Proceedings. Researchers at Mayo Clinic looked at obese patients who were in an active lifestyle intervention program designed to help them lose weight. It was determined that gut microbiota can have a role in both hindering weight loss and supporting weight loss.

Gut Microbiota More Complicated than Previously Thought

The Mayo researchers determined “an increased abundance of Phascolarctobacterium was associated with [successful weight loss]. In contrast, an increased abundance of Dialister and of genes encoding gut microbial carbohydrate-active enzymes was associated with failure to [lose] body weight. A gut microbiota with increased capability for carbohydrate metabolism appears to be associated with decreased weight loss in overweight and obese patients undergoing a lifestyle intervention program.”

How do bacteria impede weight loss? Vandana Nehra, MD, Mayo Clinic Gastroenterologist and co-senior author of the study, explained in a news  release.

“Gut bacteria have the capacity to break down complex food particles, which provides us with additional energy. And this is normally is good for us,” she says. “However, for some individuals trying to lose weight, this process may become a hindrance.”

Put another away: people who more effectively metabolized carbohydrates were the ones who struggled to drop the pounds, New Atlas pointed out.

Vandana Nehra, MD (left), and Purna Kashyap, MBBS (right), are Mayo Clinic Gastroenterologists and co-senior authors of the Mayo study. “While we need to replicate these findings in a bigger study, we now have an important direction to pursue in terms of potentially providing more individualized strategies for people who struggle with obesity,” Nehra noted in the news release. Thus, precision medicine therapy for obese individuals could be based on Mayo Clinic’s research. (Photo copyright: Mayo Clinic.)

Mayo Study Provides Clues to Microbiota Potential in Weight Loss

The Mayo researchers wanted to know how gut bacteria behave in people who are trying to lose weight.

They recruited 26 people, ranging in age from 18 to 65, from the Mayo Clinic Obesity Treatment Research Program. Fecal stool samples, for researchers’ analysis, were collected from participants at the start of the three-month study period and at the end.  The definition of successful weight loss was at least 5% of body weight.

Researchers found the following, according Live Science:

  • 2 lbs. lost, on average, among all participants;
  • Nine people were successful, losing an average of 17.4 lbs.;
  • 17 people did not meet the goal, losing on average just 3.3 lbs.; and,
  • More gut bacterial genes that break down carbohydrates were found in stool samples of the unsuccessful weight loss group, as compared to the successful dieters.

The researchers concluded that “An increased abundance of microbial genes encoding carbohydrate-active enzyme pathways and a decreased abundance of Phascolarctobacterium in the gut microbiota of obese and overweight individuals are associated with failure to lose at least 5% weight following a 3-month comprehensive lifestyle intervention program.”

Purna Kashyap, MBBS, Mayo Clinic Gastroenterologist and co-senior author of the study, told Live Science, “The study suggests there is a need to take the microbiome into account in clinical studies (on weight loss), and it also provides an important direction to pursue in terms of providing individualized care in obesity.” The very basis of precision medicine.

Future Weight-Loss Plans Based on Patient’s Microbiota

The Mayo Clinic researchers acknowledged the small sample size and need for more studies with larger samples over a longer time period. They also noted in their paper that Dialister has been associated with oral infections, such as gingivitis, and its role in energy expenditure and metabolism is unclear.

Still, the study suggests that it may soon be possible to give people individualized weight loss plans based on their gut bacteria. Clinical laboratory professionals and pathologists will want to stay abreast of follow-up studies and replication of findings by other research teams. A future medical laboratory test to analyze patients’ microbiomes could help obese people worldwide as well as lab business volume.

—Donna Marie Pocius

Related Information:

Gut Microbial Carbohydrate Metabolism Hinders Weight Loss in Overweight Adults Undergoing Lifestyle Intervention with a Volumetric Diet

Gut Microbiota from Twins Discordant for Obesity Modulate Metabolism in Mice

CDC: Adult Obesity Facts

Makeup of an Individual’s Gut Bacteria May Play Role in Weight Loss, Mayo Study Suggests

Struggle to Lose Weight? Your gut Bacteria May Be to Blame

Your Gut Bacteria May Make It Harder to Lose Weight

Diet Hit a Snag? Your Gut Bacteria May be Partly to Blame

Can’t Lose Weight? Your Gut Bacteria Could be to Blame, According to Study

Richness of Human Gut Microbiome Correlates with Metabolic Markers

Annual Medical Spending Attributable to Obesity: Payer- and Service-Specific Estimates

5 Ways Gut Bacteria Affect Your Health

Cornell Researchers Identify Gut Microbes That May Help Some People Remain Thin; Findings Could Result in Clinical Laboratory Tests to Analyze Microbiomes of Individuals

Clinical Laboratories Might Soon be Diagnosing Obesity and Guiding Therapies that Utilize Engineered Microbes

Researchers in Two Separate Studies Discover Gut Microbiome Can Affect Efficacy of Certain Cancer Drugs; Will Findings Lead to a New Clinical Laboratory Test?

If the link between certain types of gut bacteria and improved effectiveness of certain cancer treatments can be leveraged, then medical laboratories could soon have another diagnostic tool to use in supporting physicians with cancer care

From improving treatments for chronic diseases to extending lives, gut microbiome (bacteria that is part of human microbiota) has been at the forefront of developing clinical laboratory testing and anatomic pathology diagnostic technologies in recent years. Now, two studies recently published in the online journal Science confirm research that the “composition” of gut bacteria may have a significant influence on the effectiveness of certain cancer drugs.

The goal of both studies was to determine whether there was a link between gut bacteria and the efficacy of cancer drugs known as PD-1 inhibitors. These drugs are used for several types of cancer, including:

  • Melanoma;
  • Lung;
  • Bladder; and,
  • Stomach cancers.

They function by freeing up the immune system to attack cancer cells.

Greater Bacterial Diversity in Gut Brings Improved Response to PD-1 Inhibitors

One of the studies, “Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients,” found that a microbiome populated with “good” bacteria can elevate the potency of certain drug treatments. The researchers discovered that the gut bacteria in patients who responded well to PD-1 inhibitors differed from that found in patients who did not respond to the treatment.

For this study, researchers at the MD Anderson Cancer Center at the University of Texas collected oral, gut, and fecal microbiome samples and tumor biopsies from 112 patients with advanced melanoma. Clinical laboratorians took the samples before and after PD-1 treatments. They divided the patients into two groups—responders and non-responders—and profiled each microbiome using genetic sequencing.

“What we found was impressive: There were major differences both in the diversity and composition of the gut microbiome in responders versus non-responders,” Jennifer Wargo, MD, MMSc, leader of the study, told STAT. “Those who did well had greater bacterial diversity in their gut, whereas those whose tumors didn’t much shrink had fewer varieties of microbes present.”

Melanoma patients who experienced success with PD-1 therapy had a more diverse microbiome and higher concentrations of bacteria known as Ruminococcus and Faecalibacterium. Patients involved in the study who did not respond well to PD-1 therapy had the presence of another bacterium called Bacteroidales.

Jennifer Wargo, MD (above center) with her team at the MD Anderson laboratories. The researchers cautioned that clinical trials are needed before a definitive conclusion can be reached on whether altering gut bacteria can improve the effectiveness of PD-1 therapy. “If you’re changing the microbiome, depending on how you do it, it may not help you—and it might harm you,” Wargo emphasized in STAT. “Don’t try this at home.” (Photo copyright: MD Anderson.)

Antibiotics Can Reduce Effectiveness of PD-1Therapy

The other study, “Gut Microbiome Influences Efficacy of PD-1-based Immunotherapy Against Epithelial Tumors,” discovered that some drug therapies were less effective in patients who were also taking antibiotics to treat infections shortly before beginning treatment with PD-1 drugs.

Researchers for this study, led by Laurence Zitvogel, MD, PhD, of the Gustave Roussy Cancer Campus in Villejuif, France, examined 249 patients who were given a PD-1 inhibitor for lung, kidney, or urinary tract cancers. A little over one fourth of these patients had recently taken antibiotics, which can strip the gut of essential bacteria necessary to treat infections.

The team found that patients who had ingested an antibiotic relapsed faster and did not live as long as patients who had not taken an antibiotic before receiving PD-1 therapy. When they analyzed variances between patients who responded well to treatment versus patients who did not, they detected the presence of Akkermansia muciniphila, a mucin-degrading bacterium, in the responders.

Personalized Treatment Based on Each Patient’s Gut Microbiome

The culmination of this type of research raises questions about how cancer medications may interact with microbiomes.

“Should we be profiling the gut microbiome in cancer patients going into immunotherapy?” asked Wargo in the STAT article. “And, should we also be limiting, or closely monitoring, the antibiotic use in these patients?

“This is all very context-specific, and multiple different factors need to be considered on how best to change the microbiome,” she continued. “When it comes to optimizing cancer therapy, treatments will have to be heavily personalized, based on what a patient’s gut microbiome looks like already.”

Diagnostic tests that could determine whether a certain drug will be beneficial for a patient would perform a critical role in healthcare decision-making. Since cancer drug treatments can cost tens of thousands of dollars or more, it would be advantageous to know which therapies would be optimal for individual patients. The hope is that in the future, clinicians, working with anatomic pathologists and clinical laboratories, will have the tools needed to ascertain if patient’s microbiomes will best work with a particular drug and if they would likely encounter any side effects.

—JP Schlingman

Related Information:

Patients’ Gut Bugs May Play Role in Cancer Care

Gut Microbiome Modulates Response to Anti–PD-1 Immunotherapy in Melanoma Patients

Gut Microbiome Influences Efficacy Of PD-1–Based Immunotherapy Against Epithelial Tumors

Your Gut Bacteria Could Determine How You Respond to Cutting-edge Cancer Drugs

The Bacteria in Your Gut Could Help Determine if a Cancer Therapy Will Work

Attention Microbiologists and Medical Laboratory Scientists: New Research Suggests an Organism’s Microbiome Might Be a Factor in Longer, More Active Lives

Get the Poop on Organisms Living in Your Gut with a New Consumer Laboratory Test Offered by American Gut and uBiome

Mayo Clinic and Whole Biome Announce Collaboration to Research the Role of the Human Microbiome in Women’s Diseases Using Unique Medical Laboratory Tests

Precision Healthcare Milestone Reached as Food and Drug Administration Clears New Multi-Marker Medical Laboratory Test to Detect Antibiotic-Resistant Bacteria

FDA issues press release following clearance of a clinical lab test to detect genetic markers that indicate the presence of Carbapenem-resistant Enterobacteriaceae

Clearance by the US Food and Drug Administration (FDA) of a new rapid, multi-marker genetic test designed to identify bacteria that are resistant to Carbapenem antibiotics was considered significant enough that the federal agency issued a press release announcing that the test was cleared and now available for use by physicians and clinical laboratories in the United States.

In the race to develop molecular assays and genetic tests for infectious disease that deliver improved sensitivity and specificity with a faster time-to-answer, this new test offers all three benefits. Results are available in just 48 minutes, for example.

It was on June 29, 2016, that the FDA cleared Cepheid’s Xpert Carba-R rapid-diagnostic test for marketing in the United States. This is the first clinical laboratory test cleared for market by the FDA that detects healthcare-associated infections (AKA, hospital-acquired infections or HAIs) through the use of genetic markers taken directly from clinical samples. The assay tests for genetic markers that indicate the presence of Carbapenem-resistant Enterobacteriaceae (CRE). (more…)

Get the Poop on Organisms Living in Your Gut With a New Consumer Laboratory Test Offered by American Gut and uBiome

American Gut is using test results to create a microbiome database for use by researchers to better understand how microbes impact human health

Have you ever wondered what lurks in the dark corridors of your bowels? Now you can find out. Two entrepreneurial organizations—one a not-for-profit and the other a new clinical lab company—are charting new medical laboratory territory with the offer of an inexpensive poop test that reveals the type of microbes residing in your gut.

Where to Get Your Gut Microbes Analyzed

The not-for-profit organization American Gut, or British Gut in the United Kingdom (UK), which launched as crowd-funding projects on FundRazr, involve a private research project called the Human Food Project (HFP), which was initiated to compare the microbiomes of populations around the world. The Human Food Project is seeking a better understanding of modern disease by studying the coevolution of humans and their microbes.

People who pay American Gut’s $99 test fee (£75 for the UK project) receive a test kit to collect a stool sample to mail back for DNA sequencing. The test results will be provided to participants, but also benefit microbiome research. (more…)

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