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Researchers Use Whole Genome Sequencing to Make Surprising Discovery about Hospital-Acquired C. Diff Infections

By analyzing strains of the bacterium from a hospital ICU, the scientists learned that most infections were triggered within patients, not from cross-transmission

Tracking the source of Hospital-acquired infections (HAI) has long been centered around the assumption that most HAIs originate from cross-transmission within the hospital or healthcare setting. And prevention measures are costly for hospitals and medical laboratories. However, new research puts a surprising new angle on a different source for some proportion of these infections.

The study suggests that most infections caused by Clostridioides difficile (C. Diff), the bacterium most responsible for HAIs, arise not from cross-transmission in the hospital, but within patients who already carry the bacterium.

The research team, led by immunologist Evan Snitkin, PhD, and microbiologist Vincent Young, MD, PhD, both from the University of Michigan (UM), and epidemiologist Mary Hayden, MD, of Rush University Medical Center in Chicago, analyzed fecal samples from more than 1,100 patients in Rush Medical Center’s intensive care unit over a nine-month period.

A researcher performed whole genome sequencing on 425 strains of the bacterium isolated from the samples and found “very little evidence that the strains of C. diff from one patient to the next were the same, which would imply in-hospital acquisition,” according to a UM news story.

“In fact, there were only six genomically supported transmissions over the study period. Instead, people who were already colonized were at greater risk of transitioning to infection,” UM stated.

Arianna Miles-Jay, PhD, a postdoctoral fellow in The Snitkin Lab at the University of Michigan and Manager of the Genomic Analysis Unit at the Michigan Department of Health and Human Services, performed the genomic sequencing. “By systematically culturing every patient, we thought we could understand how transmission was happening. The surprise was that, based on the genomics, there was very little transmission,” she said in the UM news story.

The researchers published their findings in the journal Nature Medicine titled, “Longitudinal Genomic Surveillance of Carriage and Transmission of Clostridioides Difficile in an Intensive Care Unit.”

Evan Snitkin, PhD

“Something happened to these patients that we still don’t understand to trigger the transition from C. diff hanging out in the gut to the organism causing diarrhea and the other complications resulting from infection,” said Evan Snitkin, PhD (above), Associate Professor of Microbiology and Immunology, and Associate Professor of Internal Medicine, Division of Infectious Diseases at University of Michigan, in a UM news story. Medical laboratories involved in hospital-acquired infection prevention understand the importance of this research and its effect on patient safety. (Photo copyright: University of Michigan.)

Only a Fraction of HAIs Are Through Cross-Transmission

In the study abstract, the researchers wrote that “despite enhanced infection prevention efforts, Clostridioides difficile remains the leading cause of healthcare-associated infections in the United States.”

Citing data from the US Centers for Disease Control and Prevention (CDC), HealthDay reported that “nearly half a million C. diff infections occur in the United States each year. Between 13,000 and 16,000 people die from the bacterium, which causes watery diarrhea and inflammation of the colon. Many of these infections and deaths have been blamed on transmission between hospitalized patients.”

The new study, however, notes that 9.3% of the patients admitted to the ICU carried toxigenic (produces toxins) C. diff, but only 1% acquired it via cross-transmission. The carriers, the study authors wrote, “posed minimal risk to others,” but were 24 times more likely to develop a C. diff infection than non-carriers.

“Our findings suggest that measures in place in the ICU at the time of the study—high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff, and single patient rooms —were effective in preventing C. diff transmission,” Snitkin told HealthDay. “This indicates that to make further progress in protecting patients from developing C. diff infections will require improving our understanding of the triggers that lead patients asymptomatically carrying C. diff to transition to having infections.”

Recognizing Risk Factors

Despite the finding that infections were largely triggered within the patients, the researchers still emphasized the importance of taking measures to prevent hospital-acquired infections.

“In fact, the measures in place in the Rush ICU at the time of the study—high rates of compliance with hand hygiene among healthcare personnel, routine environmental disinfection with an agent active against C. diff, and single patient rooms—were likely responsible for the low transmission rate,” the UM news story noted.

One expert not involved with the study suggested that hospitals’ use of antibiotics may be a factor in causing C. diff carriers to develop infections.

“These findings suggest that while we should continue our current infection prevention strategies, attention should also be given to identifying the individuals who are asymptomatic carriers and finding ways to reduce their risk of developing an infection, like carefully optimizing antibiotic usage and recognizing other risk factors,” Hannah Newman, Senior Director of Infection Prevention at Lenox Hill Hospital in New York City, told HealthDay.

Snitkin, however, told HealthDay that other factors are likely at play. “There is support for antibiotic disruption of the microbiota being one type of trigger event, but there is certainly more to it than that, as not every patient who carries C. diff and receives antibiotics will develop an infection.”

Another expert not involved with the study told HealthDay that “many patients are already colonized,” especially older ones or those who have been previously hospitalized.

“A lot of their normal flora in their GI tract can be altered either through surgery or antibiotics or some other mechanism, and then symptoms occur, and that’s when they are treated with antibiotics,” said Donna Armellino, RN, Senior VP of Infection Prevention at Northwell Health in Manhasset, New York.

Whatever is taking place, hospital-acquired infections kill thousands of people every years. It’s on the federal Centers for Medicare and Medicaid Services’ (CMS) “never event” list of hospital-acquired conditions (HOC) that should never happen to hospital patients. This affects reimbursement to hospitals for treatment of infections under Medicare’s Hospital-Acquired Condition Reduction Program

This research also demonstrates the value of faster, cheaper, more accurate gene sequencing for researching life-threatening conditions. Microbiologists, Clinical laboratory scientists, and pathologists will want monitor further developments involving these findings as researchers from University of Michigan and Rush University Medical Center continue to learn more about the source of C. diff infections.

—Stephen Beale

Related Information:

The Surprising Origin of a Deadly Hospital Infection

Patient-to-Patient Transmission Not to Blame for Most C. Difficile Infections in Hospitals

Longitudinal Genomic Surveillance of Carriage and Transmission of Clostridioides difficile in an Intensive Care Unit

Could Proximity of Toilets to Sinks in Medical Intensive Care Units Contribute to Hospital-Acquired Infections?

Microbiologists will be interested to learn of new research designed to better identify sources of hospital-acquired infections, including investigating possibilities that have not been previously considered

Does the proximity of toilets to sinks in medical intensive care units (MICUs) affect the health and recovery of the patients staying there? Until recently, that wasn’t questioned. But clinical laboratory managers will be interested to learn why researchers now believe this could very well lead to nosocomial infections—also known as hospital-acquired infections (HAIs)—a topic Dark Daily has covered extensively for many years.

Researchers at the Medical College of Wisconsin (MCW), Milwaukee, found that sinks located near toilets in patient rooms were four times more likely to have Klebsiella pneumoniae carbapenemase (KPC)-producing organisms in their drains than sinks that were located farther away from toilets, according to an Elsevier press release.

In a study published in the American Journal of Infection Control (AJIC), a journal of the Association for Professionals in Infection Control and Epidemiology (APICE), the authors wrote that no other formal research had been conducted to determine whether the location of sinks in patient rooms is relevant to the spread of infections.

Thus, the results of this research could impact not only the hygiene and disinfectant procedures of healthcare workers, but the designs of future MICU rooms and possibly even change the plumbing requirements throughout entire healthcare facilities. These new findings may also create new factors for hospital infection control teams and microbiologists to consider when investigating the sources of nosocomial infections.

The MCW researchers conducted their investigation in a 600-bed Wisconsin hospital with a 26-bed MICU “in which each room has:

  • “a patient bed;
  • “two sinks; and,
  • “a toilet without physical barriers in between.

“Each room is surface-cleaned (including sink bowls, but not drains) with hydrogen peroxide/peracetic acid on a daily basis. Separate cloths are used to clean each of the two sinks in patient rooms to avoid cross-contamination,” the study notes.

Photo copyright: Medical College of Wisconsin, Milwaukee

The photo above (taken from the MCW study) illustrates the configuration of the medical intensive care unit room surveyed in this study. The location of the toilet with a sink adjacent to the toilet and sink far from the toilet are all labeled. (Photo copyright: Medical College of Wisconsin, Milwaukee.)

The MCW researchers found:

  • “KPC–producing organisms persist in sink drains in intensive care units without recent history of carbapenem-resistant Enterobacteriaceae infections;
  • “A high prevalence of [beta-lactamase Klebsiella pneumoniae carbapenemase] (blaKPC) polymerase chain reaction-positive (54%) and culture-positive (9%) sink drains; and,
  • “Sinks near toilets were four times more likely to be positive (87%) than sinks distal to toilets (22%).”

However, the MICU did not have any documented interactions with KPC-producing organisms within the past year, the press release noted.

“This study, if validated, could have major implications for infection control,” study authors, Blake Buchan, PhD (left), and Silvia Munoz-Price, MD, PhD (right), stated in the press release. “If sinks next to toilets are indeed a reservoir for KPC, additional interventions—such as modified hand hygiene practices and sink disinfection protocols—may be needed to stem the risk of transmission among healthcare providers and patients alike.” (Photos copyright: Medical College of Wisconsin.)

“This study, if validated, could have major implications for infection control,” study authors, Blake Buchan, PhD (left), and Silvia Munoz-Price, MD, PhD (right), stated in the press release. “If sinks next to toilets are indeed a reservoir for KPC, additional interventions—such as modified hand hygiene practices and sink disinfection protocols—may be needed to stem the risk of transmission among healthcare providers and patients alike.” (Photos copyright: Medical College of Wisconsin.)

Other Studies into KPCs, HAIs, and Human Gut Microbiota

Another study, which looked at the risk factors for carbapenem-resistant KPC (CRKP) in pediatric patients in Beijing Children’s Hospital, found that hematologic malignancies and previous cephalosporin administration were better predictors of mortality due to CRKP bloodstream infections than mechanical ventilation for septic shock.

And, in a study published in the Oxford Academic journal Clinical Infectious Diseases, researchers associated with the Rush University Medical Center in Chicago, and the University of Michigan Medical School, Ann Arbor, found that “increased relative abundance of Klebsiella pneumoniae carbapenemase-producing Klebsiella pneumoniae within [human] gut microbiota is associated with risk of bloodstream infection in long-term acute care hospital patients.”

Dark Daily reported on a similar study conducted at Stanford University School of Medicine last year. (See, “Stanford University Study Traces Hospital-Acquired Bloodstream Infections to Patients’ Own Digestive Tract,” November 19, 2018.)

New technologies that allow researchers to follow novel, unexplored paths to learn about potential sources of infections might contribute to fewer hospital-acquired infections and improved outcomes for both patients and those who work in healthcare settings.

Medical laboratories play a critical important role in this by identifying and typing bacteria in hospital settings, especially those that are resistant to current antibiotics. New approaches to locating such bacteria continue to be investigated and the tools available to learn more about them are becoming more powerful and widely available.

Regardless of the origin, protecting staff and patients from HAIs is critical. Clinical laboratory involvement in protecting patients, and monitoring, investigating, and managing outbreaks, are key to controlling the spread of these dangerous bacteria.

—Dava Stewart

Related Information:

A Reservoir of Bacteria: Sink Drains Next to Toilets In Patient Rooms May Harbor Dangerous Organisms

The Relevance of Sink Proximity to Toilets on the Detection of Klebsiella pneumonia Carbapenemase Inside Sink Drains

Risk Factors for Carbapenem-resistant K. pneumonia Bloodstream Infection and Predictors of Mortality in Chinese Pediatric Patients

Increased Relative Abundance of Klebsiella pneumoniae Carbapenemase-producing Klebsiella pneumoniae Within the Gut Microbiota Is Associated with Risk of Bloodstream Infection in Long-term Acute Care Hospital Patients

New Molecular Diagnostic Approaches to Bacterial Infections and antibacterial Resistance

Stanford University Study Traces Hospital-Acquired Bloodstream Infections to Patients’ Own Digestive Tract

Microbiologists Determine That Workout Warriors Are Drinking from Reusable Water Bottles Contaminated with Bacteria Found to Cause Hospital-Acquired Infections

Brazilian study finds Staph, E. coli, and other bacteria that contribute to hospital-acquired infections in reusable water bottles used by members of multiple fitness centers

In the latest example of Microbiologists swabbing and culturing samples taken from common, everyday items, a research team in Brazil has found germs associated with hospital-acquired infections (HAIs) infections on reusable water bottles carried by individuals working out in local fitness clubs. 

Dark Daily recently reported on a University of Pennsylvania Perelman School of Medicine study which showed that healthcare providers unknowingly spread deadly bacteria—including Staphylococcus aureus (Staph)—with their clothing and even stethoscopes throughout healthcare networks nationwide. Microbiologists and other clinical laboratory professionals battle HAIs that result from such contaminations every day.

The Brazilian study, which was published in the Journal of Exercise Physiology Online, the official research journal of the American Society of Exercise Physiologists (ASEP), has concluded that infrequent washing of reusable water bottles creates a reservoir of deadly germs that also include Staph and E. coli.

Their results may cause gym members to consider the impact the bottles they tote can have on their health.

Worse than Licking a Dog Toy

The researchers analyzed the presence of different bacterial strains in the water bottles of 30 fitness club members at two different fitness center locations, as well as 30 new unused bottles. They also conducted antimicrobial susceptibility tests for the isolated strains.

The scientists found contamination in 90% of the used plastic bottles, while none of the new bottles showed signs of bacterial contamination. Twenty-five (83%) of the used bottles contained Staph (26.66%) and E. coli (16.66%). In addition, four of the reused bottles tested positive for the presence Pseudomonas, an antibiotic-resistant bacterium that also causes HAIs.

“We tested in a real-world scenario, by surprise, asking for those who were arriving at the gym at those particular days, stated Gilmar Weber Senna, PhD, Professor at the Federal University of Rio de Janeiro, in a Runner’s World article. “We did this to avoid an intentional over-cleaning.”

Similar results were found in testing performed by the website That study revealed an average athlete’s water bottle contained 313,499 viable bacteria cells (313,400 colony-forming units per square centimeter).

“To put it bluntly, drinking from the average refillable bottle can be many times worse than licking your dog’s toy,” Treadmill Reviews noted.

Philip M. Tierno, Jr., Professor of Microbiology and Pathology at New York University and NYU Langone Medical Center, is not surprised by the findings of the Brazilian study, which found that 83% of fitness club members’ reusable water bottles were contaminated with bacteria. He suggests frequent handwashing before refilling reusable water bottles will help prevent spreading the bacteria. Clinical pathologists will agree that diligent cleaning of hands, clothes, and medical instruments can prevent the spread of deadly diseases. (Photo copyright: NYU Langone Health.)

CDC Downplays Presence of Staph and E. coli

Despite the ick-factor of the water-bottle testing results, Runner’s World also notes that the Centers for Disease Control and Prevention (CDC) determined that Staph bacteria can be found in the noses of 30% of the population, while E. coli is present in healthy gastro intestinal tracts, with only certain strains causing illness.

The Brazilian study’s authors also noted that most of the bacteria isolated in their research belong to the Enterobacteria group, which lives in the intestines and are pathogenic. Thus, the researchers surmised that “manipulation with contaminated hands may contribute to the colonization of the [reusable water bottles].

“We conclude the best way to avoid bacterial proliferation in the [reusable water bottles] is to make sure they are correctly and frequently cleaned, such as daily washing with neutral soup in association with proper hand hygiene to prevent contamination,” Senna and co-authors wrote.

Philip M. Tierno, Jr, PhD, Professor of Microbiology and Pathology at New York University (NYU) and the NYU Langone Medical Center supports the study’s conclusions. He suggests water bottles likely become contaminated through handling by their owners, an issue proper hand hygiene can help remedy. He recommends properly washing hands before filling a gym water bottle.

“Wash 20 seconds,” Tierno told Runner’s World. “Get soap on the top and bottom of hands and in between digits and under the nail bed. Run your hands like a claw in the center of the opposite palm to get suds into the nail bed, and sing the song ‘Happy Birthday’ twice to wash hands adequately.”

Reusable water bottles also should be cleaned thoroughly, preferably in a dishwasher.

Until the general public begins routinely following such advice, microbiologists and clinical pathologists will remain the tip of the spear in infection control programs and education. But that should not stop clinical laboratory managers from implementing constant monitoring and cleaning protocols to stop the spread of infectious bacteria in their labs.

—Andrea Downing Peck

Related Information:

Just How Filthy Is Your Reusable Water Bottle?

Microbial Contamination in Shaker Bottles among Members of Fitness Centers

A Look Under the Cap: Water Bottle Germs Revealed

Stanford University Study Traces Hospital-Acquired Bloodstream Infections to Patients’ Own Digestive Tract

CMS Missed 96 Hospitals with Suspected HAI Reporting Due to Limited Use of Analytics, OIG Report Reveals

Collaboration between Pathologists, Medical Laboratories, and Hospital Staff Substantially Reduced Hospital-Acquired Infections, AHRQ Reports

Leapfrog Group Report Shows Hospitals Failing to Eliminate Hospital-Acquired Infections; Medical Laboratories Can Help Providers’ Antimicrobial Stewardship Programs

Microbiologists Take Note! UPenn Study Using Next-Generation Sequencing Finds Stethoscopes Harbor Vast Amounts of Bacteria, Including Staphylococcus Aureus, Which Causes Deadly Hospital-Acquired Infections

Researchers also found Staph and other bacteria on stethoscopes after they had been cleaned, leading to scrutiny of cleaning agents and methods

Microbiologists, anatomic pathologists, and clinical laboratory leaders should be intrigued by a university study which found stethoscopes worn by caregivers contained vast amounts of bacteria, including Staphylococcus aureus (Staph), a major cause of hospital-acquired infections (HAIs).

Using next-generation DNA sequencing, University of Pennsylvania Perelman School of Medicine researchers found the deadly bacteria on stethoscopes stored and used in, of all places, an intensive care unit (ICU), where patients are particularly vulnerable to infection.

Even more compelling was the discovery of DNA from the Staph bacteria on the stethoscopes even after they were cleaned. Though the tests could not differentiate between live and dead bacteria, the researchers found other non-Staph bacteria as well, including Pseudomonas and Acinetobacter.

Similar conditions could no doubt be found in most healthcare settings in America, highlighting the critical importance for rigorous cleaning procedures and protocols.

The researchers published their paper in Infection Control and Hospital Epidemiology, the journal of the Society for Healthcare Epidemiology of America (SHEA).

Deadly Bacteria Becoming Harder to Kill

HAIs are becoming increasingly difficult to prevent partly because Staph bacteria, such as Methicillin-resistant Staphylococcus aureus (MRSA), are becoming increasingly resistant to antibiotics, according to the Centers for Disease Control and Prevention (CDC).

“The study underscores the importance of adhering to rigorous infection control procedures, including fully adhering to CDC-recommended decontamination procedures between patients, or using single-patient use stethoscopes kept in each patient’s room,” said Ronald Collman, MD (above), the study’s senior author and Professor of Medicine, Pulmonary, Allergy, and Critical Care at UPenn’s Perelman School of Medicine, in a news release. (Photo copyright: Penn Medicine.)

The researchers acknowledged that previous culture-based bacterial studies looked at stethoscopes, but noted the results fell short of the view next-generation sequencing technology can offer for identifying bacteria, as well as determining the effectiveness of cleaning chemicals and regiments.

“Culture-based studies, which focus on individual organisms, have implicated stethoscopes as potential vectors of nosocomial bacterial transmission [HAI]. However, the full bacterial communities that contaminate in-use stethoscopes have not been investigated,” they wrote in Infection Control and Hospital Epidemiology.

Study Employs RNA Deep-Sequencing

The UPenn researchers used bacterial 16 ribosomal RNA (16S rRNA gene) deep-sequencing to study the bacteria, Becker’s Healthcare explained.

The stethoscopes analyzed were in-use as follows:

• 20 worn by physicians, nurses, and respiratory therapists;

• 20 single patient-use disposable stethoscopes available in ICU patient rooms; and,

• 10 unused single-use disposable stethoscopes to serve as a control.

All stethoscopes worn and/or used in the ICU were found to be contaminated with abundant amounts of Staphylococcus DNA. “Definitive” amounts of Staph was found by researchers on 24 of 40 tested devices, noted MedPage Today.

“Genera relevant to healthcare-associated infections (HAIs) were common on practitioner stethoscopes, among which Staphylococcus was ubiquitous and had the highest relative abundance (6.8% to 14% of containment bacterial sequences),” the researchers noted in their paper.

Cleaning Methods Also Examined

The researchers also studied the hospital’s cleaning agents and procedures:

• 10 practitioner stethoscopes were examined before and after a standard 60-second cleaning procedure using hydrogen peroxide wipes;

• 20 additional stethoscopes were assessed before and after cleaning by practitioners using alcohol wipes, hydrogen peroxide wipes, or bleach wipes.

All methods reduced bacteria. But not to the levels of a new stethoscope, the study showed.

“Stethoscopes used in an ICU carry bacterial DNA reflecting complex microbial communities that include nosocomially important taxa. Commonly used cleaning practices reduce contamination but are only partially successful at modifying or eliminating these communities,” the researchers concluded in their paper.

Prior Studies to Find and Track Dangerous Bacteria

Studies tracking bacteria where people live, work, and travel are not new. For years, medical technologists and microbiologists have roamed the halls of hospitals and other clinical settings to swab and culture different surfaces and even articles of clothing. These efforts are often associated with programs to reduce nosocomial infections (HAIs).

One such study revealed that about 47% of neckties worn by clinicians carried HAIs, according to a New York Hospital Medical Center (now New York-Presbyterian Queens) study. Dark Daily reported on this finding 10 years ago. (See, “Antibiotic Neckties Are Latest Healthcare Fashion Trend,” May 25, 2007.)

And, on a larger scale, in 2013, researchers at Weill Cornell Medical College in New York City (NYC) used next-generation gene sequencing to track pathogens in the NYC subway system. The project, called PathoMap, involved collecting 1,404 surface samples from 468 NYC subway stations to develop a system for spotting and tracking potential microbial threat due to bioterrorism or emergent disease. (See, “Microbiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways,” December 13, 2013.)

This new study by UPenn Perelman School of Medicine researchers—published in a peer-reviewed medical journal—will hopefully serve as a contemporary reminder to doctors and other caregivers of how bacteria can be transmitted and the critical importance of cleanliness, not only of hands, but also stethoscopes (and neckties).  

Hospital-based medical laboratory leaders and microbiology professionals also can help by joining with their infection control colleagues to advocate for CDC-recommended disinfection and sterilization guidelines throughout their healthcare networks.

—Donna Marie Pocius

Related Information:

Molecular Analysis of Bacterial Contamination on Stethoscopes in an Intensive Care Unit

Stethoscopes Loaded with Bacteria, Including Staphylococcus

ICU Stethoscopes Teeming with Bacteria

Bacteria Remains After Cleaning Stethoscopes: Four Study Insights

Predictors of Heavy Stethoscope Contamination Following a Personal Examination

Centers for Disease Control and Prevention: Guidelines for Disinfection of Healthcare Equipment

Antibiotic Neckties are Latest Healthcare Fashion TrendMicrobiologists at Weill Cornell Use Next-Generation Gene Sequencing to Map the Microbiome of New York City Subways

Stanford University Study Traces Hospital-Acquired Bloodstream Infections to Patients’ Own Digestive Tract

New bioinformatic tool finds gut microbiota may be ‘potential reservoir of bloodstream pathogens’ suggesting patients’ own bodies can be source of infections

Clinical laboratories in hospitals and health networks throughout the nation are collaborating in the priority effort to reduce deaths from sepsis and related blood infections. Now comes news that researchers at Stanford have identified an unexpected source of bloodstream infections. This finding may help medical laboratories contribute to faster and more accurate diagnoses of blood infections, particularly for hospital inpatients.

Lax infection-control practices often are blamed for hospital-acquired infections (HAIs). And HAIs certainly have been responsible for many tragic avoidable deaths. However, new research from Stanford University School of Medicine shows that hospital staff, other patients, or unclean instruments may not be solely responsible for all infections that present during hospital stays. According to Stanford researchers, a patient’s own digestive tract can be the surprising culprit for many bloodstream infections. This finding confirms a common belief that the patient’s microbiome probably is involved in many blood infections.

Clinical pathologists have become vital players in infection prevention programs, as hospitals intensify their focus on reducing HAIs. That’s especially in light of the Centers for Medicare and Medicaid Services (CMS) implementation of the pay-for-performance Hospital-Acquired Condition (HAC) Reduction Program. Now, Stanford researchers have found that for many hospital patients their own bodies may be the source of infections.

The researchers published their findings in Nature Medicine.

Bacteria Causing Blood Infections Found in Patients’ Stool Samples After Bone Marrow Transplants

Using a new bioinformatic computational tool called StrainSifter, the Stanford University team rapidly and accurately identified a surprising infection source in a group of hospitalized patients—microbes already living in the patients’ large intestines—a Stanford University news release explained.

The researchers analyzed blood and stool samples from 30 patients who developed bloodstream infections after receiving bone marrow transplants between October 2015 and June 2017 at Stanford Hospital. The researchers sought to determine whether the bacteria isolated from the patients’ blood also was found in stool specimens that had been collected prior to the transplants. The process required sequencing not only the patients’ DNA, but also analyzing the genomes of all the individual microbial strains resident in each patient’s stool.

“Just finding E. coli in a patient’s blood and again in the patient’s stool doesn’t mean they’re the same strain,” Ami Bhatt, MD, PhD, Assistant Professor of Hematology and Genetics at Stanford, explained in the news release. Bhatt served as senior author of the study. (Photo copyright: Stanford University.)

Analysis found that more than one-third of the patients’ stool samples (11) contained detectable levels of the same bacterial strain that had caused those patients’ bloodstream infections.

“Because the gut normally harbors more than 1,000 different bacterial strains, it’s looked upon as a likely culprit of bloodstream infections, especially when the identified pathogen is one known to thrive inside the gut,” Ami Bhatt, MD, PhD, Assistant Professor of Hematology and Genetics at Stanford, said in the news release. “But while this culpability has been assumed—and it’s an entirely reasonable assumption—it’s never been proven. Our study demonstrates that it’s true.”

Clinical and DNA data confirmed the gastrointestinal presence of Escherichia coli and Klebsiella pneumonia, common causes of pneumonia, urinary tract infections, and other potentially serious conditions. In addition, they found other disease-causing pathogens in the gut that they would not have expected to be there.

“We also find cases where typically nonenteric [outside the intestine] pathogens, such as Pseudomonas aeruginosa and Staphylococcus epidermidis, are found in the gut microbiota, thereby challenging the existing informal dogma of these infections originating from environmental or skin sources,” Fiona Tamburini, a senior graduate student, and postdoctoral scholar Tessa Andermann, MD, MPH, Infectious Disease Medical Fellow, wrote in Nature Medicine.

New Tool for Precision Medicine

Bhatt believes being able to trace the source of bloodstream infections will help doctors provide more targeted treatments for HAIs and potentially lead to effective prevention methods. This will create a new opportunity for microbiology laboratories to provide the necessary diagnostic tests designed to guide therapeutic choices of attending physicians.

“Until now, we couldn’t pinpoint those sources with high confidence,” Bhatt said in the news release. “That’s a problem because when a patient has a bloodstream infection, it’s not enough simply to administer broad-spectrum antibiotics. You need to treat the source, or the infection will come back.”

Bhatt says the computational tool has the potential to allow medical practitioners to quickly identify whether a pathogen responsible for a patient’s bloodstream infection came from a break in the skin, leaked through the intestinal wall into the blood, or was passed on through an inserted catheter or other object.

Bhatt’s team focused on the intestines for their study because it’s the home of 1,000 to 2,000 different germs. Dark Daily has reported often on developments involving human gut bacteria (AKA, microbiome) in e-briefings going back to 2013. While these gut bacteria do not typically cause problems, Bhatt said, “It’s only when they show up in the wrong place—due, for example, to leaking through a disrupted intestinal barrier into the bloodstream—that they cause trouble.”

Because nearly 40% of immunocompromised patients who spend up to six weeks in a hospital develop bloodstream infections, the Stanford findings could signal a major breakthrough in preventing HAIs. However, larger studies are needed to validate the researchers’ contention that the gut is a “potential reservoir of bloodstreams pathogens.”

If true, microbiologists and clinical pathologists may in the future have a new method for helping hospitals identify, track, and treat blood-born infections as well as and preventing HAIs.

—Andrea Downing Peck

Related Information: 

Study Traces Hospital-Acquired Bloodstream Infections to Patients’ Own Bodies

Hospital-Acquired Condition Reduction Program Fiscal Year 2019 Fact Sheet

Precision Identification of Diverse Bloodstream Pathogens in the Gut Microbiome

Multiple Dark Daily E-briefings on Human Gut Bacteria (Microbiome)