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
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)
Decline in hospital-acquired conditions (HACs) overall since 2010 attributed to increased attention to safety protocols and practices by hospital staff in cooperation with clinical laboratory services
It’s now been almost nine years since the Medicare Program stopped paying hospitals and other providers for certain hospital-acquired conditions (HACs). Included in this list are hospital-acquired infections (HAIs). The goal is to substantially reduce the number of HACs and HAIs, thus improving patient outcomes, while substantially reducing the healthcare costs associated with these conditions.
So, almost nine years into these programs, has there been progress on these goals? This is a question of key interest to Medical laboratories and pathology groups because they have a front-line role in working with clinicians to diagnose and treat HAIs, while also looking to identify the transmission of HAIs within the hospital.
A recent report by the Agency for Healthcare Research and Quality (AHRQ), a division of the US Department of Health and Human Service (HHS), indicates that there has been progress in the goal of reducing HACs. The AHRQ report noted a 21% decline in HACs between 2010 and 2015. Data collected during that time indicates a reduction of more than 3.1 million HACs and nearly 125,000 patient deaths due to HACs.
In 2015 alone, nearly one million fewer HAC incidents occurred. The reduction saved “approximately $28 billion in healthcare costs,” an outcome which, the AHRQ report notes, is the result of increased attention to safety protocols in hospitals and a “period of concerted effort by hospitals throughout the country to reduce adverse events.”
Clinical Pathologists/Laboratories Play Key Role in HAI Prevention
Though many reported incidents are associated with adverse drug events, HAIs have been significantly reduced in recent years due to focused efforts on infection prevention. The report notes that clinical pathologists have become vital players in infection prevention programs, and that increased coordination between hospital medical laboratories and clinicians played a crucial role in the reduction.
Eileen O’Rourke is an Infection Preventionist at the Lankenau Medical Center in Philadelphia. And she has served as a leader and consultant for hospital-based infection prevention programs in Pennsylvania since 1984. In an article on the Wolters Kluwer Pharmacy OneSource blog, O’Rourke noted that successful infection prevention and control requires development of “a highly visible and administratively supported infection prevention and control program with qualified and trained personnel.” Clinical pathologists are part of that support team, providing surveillance, testing, and interpretation of data essential for identifying epidemiological origins of infection and pathogen distribution. And the vital services that clinical laboratories provide to reduce HAIs center on surveillance, prevention, and control.
The chart above was calculated on US Dollars in 2012. Since then, thanks to contributions by medical laboratories and pathologists in collaboration with hospitals, those costs have decreased significantly. (Image copyright: MLive.com.)
In an article for Lab Testing Matters, John Daly MD, Chief Medical Officer at the Commission on Office Laboratory Accreditation, and former Director of Clinical Laboratories for the Duke University Health System, highlights the importance of surveillance. He states that it is “an essential element of an infection control program” providing “data to identify infected patients and determine the site of infection” as well as “factors that contributed to the infection.” Medical laboratories must, Daly stresses, provide “easy access to high-quality and timely data and give guidance and support on how to use its resources for epidemiologic purposes.”
Daly argues that medical laboratories function as liaisons to clinical services, working to “improve the quality of specimens sent to the laboratory and promoting appropriate use of cultures and other laboratory tests.” The laboratory should, according to Daly, be involved in all aspects of the infection control programs. This ensures:
- Proper specimen collection;
- Accurate and rapid testing; and
- Accurate reporting of laboratory data.
Laboratory Data Provide ‘Early Warning’ for HAI Surveillance Systems
Robert A. Weinstein, MD, wrote in his 1978 article, “The Role of the Microbiology Laboratory in Surveillance and Control of Nosocomial Infections,” that medical laboratories and pathologists are central to prevention and control of HAIs. Laboratory records, Weinstein remarked, serve as important data sources that can identify early spread of infection, thus becoming an “early warning system” for a potential outbreak of infections. The sampling that laboratories perform identifies not only the strain of infection, but the method by which infection is spread, and the best treatment options. Nearly 40 years later his statements ring truer than ever, as anatomic pathology laboratory data continues to reveal patterns of infection faster and more precisely than ever before.
Sarah Mahoney, PhD, is a research scientist at Navitor Pharmaceuticals in Cambridge, Mass. In an article published in the American Journal of Clinical Pathology, she states that in surveilling patterns of infection, pathologists also decipher the source of infection. Mahoney wrote that it is “necessary to identify the causative organism” for surveillance and management control of HAIs. She also noted that pathologists must strive to discriminate between “hospital- and community-acquired infection” in order to provide clinicians with guidance for treatment, and to map “infection transmission within a clinical setting.”
Hospitals Rely on Medical Laboratories and Pathologists to Help Reduce HAIs
The concerted effort to reduce HACs and HAIs was inspired by incentives put forth by the US government. In 2008-2009, the Centers for Medicare and Medicaid Services (CMS) ceased paying for hospital-acquired conditions, including HAIs. Since that time, hospitals have worked to prevent and better manage HAIs. In the years since those incentives went into effect, hospitals have increasingly relied on medical laboratories and pathologists to provide necessary testing to prevent HAIs.
The CDC’s Antimicrobial Stewardship Programs create a further need for lab professionals to be involved in the identification, prevention, and treatment of HAIs. The core elements of the program state that the role of diagnostic laboratory testing—especially rapid diagnostic tests—is imperative in providing the necessary data needed to combat HAIs. The pressure is on for hospitals to reduce HAIs further to save lives and reduce costs. Thus, there is increased pressure on medical laboratories as well.
In an article in the College of American Pathologists’ online journal Cap Today,
Larry Massie, MD, Professor of Pathology at the University of New Mexico, and Chair of Pathology and Laboratory Medicine for the New Mexico VA Health Care System in Albuquerque, states that turn-around time is crucial for HAIs, but that laboratories often have difficulty keeping up with large volumes of samples. Massie suggests the use of new technologies could speed up turnaround time, particular for large healthcare providers.
The fight to reduce HAIs and HACs is showing significant progress, and clinical laboratories, working in tandem with clinicians and prevention programs, are a fundamental part of the success of HAI reduction. Clinical pathologists and laboratories often are the front line in prevention and management of HAIs, and the work they do in identifying infections is essential in the assessment and control of those infections.
— Amanda Warren
National Scorecard on Rates of Hospital-Acquired Conditions 2010 to 2015: Interim Data from National Efforts to Make Health Care Safer
How Hospitals Can Reduce Hospital-Acquired Infections
HAI Data and Statistics
Hospital Acquired Infection: Molecular Study and Infection Control Guidelines
Rapid Sequencing and Characterization of Pathogens in Hospital-Acquired Infections
The Role of the Microbiology Laboratory in Surveillance and Control of Nosocomial Infections
Core Elements of Hospital Antibiotic Stewardship Program
Pressure’s on to Halt Nosocomial Infections
Hospital Acquired Infections
Surveillance of Hospital-acquired Infections: A Model for Settings with Resource Constraints
The Laboratory and Infection Control
Role of the Microbiologist in Infection Control and Hospital Epidemiology
Study Finds Occupying Hospital Bed Previously Used by Patient Receiving Antibiotics Increases Odds of Developing C.diff Infection
Medicaid policy takes effect on July 1, 2012, and mirrors existing Medicare policy
Medicare was the first government program to announce that it would not reimburse hospitals for certain hospital-acquired conditions. Pathologists will be interested to learn that the Medicaid program is now prepared to institute a similar non-reimbursement policy. This fulfills a Dark Daily prediction that other government and private health programs would copy this Medicare policy.
As of July 1, 2012, Medicaid will no longer reimburse hospitals for treatment of certain hospital-acquired conditions (HAC). The Centers for Medicare and Medicaid Services (CMS) published its final rule on June 6th as a way of aligning Medicaid’s HAC policies with those of the Medicare program. The new Medicaid HAC rule becomes a baseline policy on top of which States can still attach their own HAC reimbursement restrictions.
American Hospital Association claims accuracy of posted HAC data not established
In further step to create transparency in patient outcomes delivered by individual hospitals, the Centers for Medicaid and Medicare Services (CMS) has posted on its website information on eight hospital-acquired conditions (HAC). However, many hospital industry leaders were not happy with this action.
The CMS data is specific to individual healthcare facilities that treat Medicare patients. It includes info on two types of hospital-acquired infections (HAI), blood compatibility, and air embolisms. Pathologists and clinical laboratory managers will recognize that medical laboratory testing plays an important role in diagnosing and monitoring several of these conditions.
That’s not news to pathologists, who often see how physicians mis-order or mis-interpret clinical laboratory tests
Each month, one out of seven Medicare patients is injured or killed by their healthcare providers. These medical errors cost taxpayers hundreds of millions of dollars each year. And, that doesn’t even include the cost of follow-up care for the injured patients who survive.
Those and other conclusions are part of a recently released study by the Department of Health and Human Services (HHS) Office of Inspector General (OIG) titled “Adverse Events in Hospitals: National Incidence Among Medicare Beneficiaries.”