Some ‘Hospital-Acquired’ Infections Traced to Patient’s Own Microbiome

Posted on October 23rd, 2018 by Dr. Francis Collins

While being cared for in the hospital, a disturbingly large number of people develop potentially life-threatening bloodstream infections. It’s been thought that most of the blame lies with microbes lurking on medical equipment, health-care professionals, or other patients and visitors. And certainly that is often true. But now an NIH-funded team has discovered that a significant fraction of these “hospital-acquired” infections may actually stem from a quite different source: the patient’s own body.

In a study of 30 bone-marrow transplant patients suffering from bloodstream infections, researchers used a newly developed computational tool called StrainSifter to match microbial DNA from close to one-third of the infections to bugs already living in the patients’ large intestines [1]. In contrast, the researchers found little DNA evidence to support the notion that such microbes were being passed around among patients.

About 1 in 50 American patients will acquire at least one infection during their hospital stays [2]. Such infections are responsible for tens of thousands of deaths each year, making them a leading cause of mortality in the United States [3].

Hospital-acquired infections caught the attention of Ami Bhatt, Stanford University, Palo Alto, CA, during her medical residency in internal medicine. When her patients developed a bloodstream infection, Bhatt naturally wanted to address the source of infection. But she found that determining the source could be complicated.

While thinking about possible sources of hospital-acquired infections, Bhatt considered the microbiome, the thousands of microbes that naturally live in and on the human body. The microbiome is increasingly recognized for its many essential roles in our metabolism, our immunity, and even our mental health. She wondered whether microbes from the microbiome might invade the bloodstream of some patients, especially those whose immune systems were already compromised.

Bhatt and colleagues, including first authors Fiona Tamburini and Tessa Andermann, focused on the gut, the natural habitat for many hundreds of diverse microbial species. Her team enrolled a total of 30 patients undergoing bone marrow transplants at Stanford University Hospital and collected from them weekly stool samples, each with an abundance of microbial life from the gut.

Bone marrow transplant patients take medications to suppress the immune system. That’s done to discourage their bodies from attacking precious donor cells. But being immunocompromised, patients are also at increased risk for infection.

Each time a transplant patient developed a bloodstream infection within 30 days of having the gut microbes collected from his or her stool samples, the researchers grew the infection-causing bacterium from the blood and sequenced its DNA.

The next step was to look for an exact DNA match between the infection-causing bacterium and one in the patient’s stool sample. That would indicate the infection-causing microbe came from the gut microbiome.

While conceptually simple, it was anything but easy. They had to compare the DNA of a single bacterial strain to all the DNA data extracted from the hundreds of microbial residents in the patient’s gut microbiome. The analysis also required extreme precision. The researchers liken the challenge to reassembling many hundreds of different photographs that had been chopped into small pieces, mixed together, and then shaken up before attempting to match them to some other photo.

The researchers managed this daunting task using their StrainSifter tool. Their analysis showed that one-third of the stool samples contained precisely the same microbial strain that made the patients ill. Interestingly, there was scant evidence that those strains were also found in the blood or stool of other patients in the same hospital. In other words, the bugs didn’t appear to be spreading from person to person.

The findings suggest that rather than “catching” an infection from the environment or another person, many of the patients were becoming ill due to a microbial imbalance within their own bodies. Bhatt noted that the study participants were often heavily treated with antibiotics and other medications in the hospital. Without careful management, their bodies could become breeding grounds for infectious and antibiotic-resistant bacteria.

In fact, the clinical and DNA data confirmed the gastrointestinal presence of antibiotic-resistant strains of Escherichia coli and Klebsiella pneumonia, common causes of severe pneumonia, urinary tract infections, and other potentially serious conditions. In the guts of those bone marrow transplant patients, they also found other disease-causing pathogens not normally found in the gut.

While optimal sanitary practices remain critical, the findings suggest preventing hospital-acquired infections could be more complicated than once thought. Correctly pinpointing the source of an infection may require more thoughtful consideration and care for each patient’s own unique microbiome. The good news is the emerging ability to trace the source of bloodstream infections will help health-care providers devise more targeted and effective methods to prevent and manage hospital-acquired infections in the future.

References:

[1] Precision identification of diverse bloodstream pathogens in the gut microbiome. Tamburini FB, Andermann TM, Tkachenko E, Senchyna F, Banaei N, Bhatt AS. Nat Med. 2018 Oct 15. doi: 10.1038/s41591-018-0202-8.

[2] Health-care Associated Infection Data. Centers for Disease Control and Prevention.

3] Estimating health care-associated infections and deaths in U.S. hospitals, 2002. Klevens RM, Edwards JR, Richards CL Jr, Horan TC, Gaynes RP, Pollock DA, Cardo DM. Public Health Rep. 2007 Mar-Apr;122(2):160-6.

Links:

Human Microbiome Project (NIH)

Bhatt Lab (Stanford University, Palo Alto, CA)

NIH Support: National Center for Advancing Translational Sciences; National Cancer Institute