A study by researchers at Washington University School of Medicine in St. Louis has found evidence that points to an unexpected source of bacteria that can cause hospital-associated infections: the hospitalized patients themselves, even when no bacteria are detectable in the bladder beforehand. The study results indicated that inserting sterile catheters into the urinary tracts of mice can result trigger dormant Acinetobacter baumannii bacteria that were hidden in the animals’ own bladder cells to emerge, multiply, and cause urinary tract infections (UTIs).
The findings, reported in Science Translational Medicine, suggest that screening patients for hidden reservoirs of dangerous bacteria could supplement infection-control efforts and help prevent deadly infections. “You could sterilize the whole hospital, and you would still have new strains of A. baumannii popping up,” said Mario Feldman, PhD, a professor of molecular microbiology. “Cleaning is just not enough, and nobody really knows why. This study shows that patients may be unwittingly carrying the bacteria into the hospital themselves, and that has implications for infection control. If someone has a planned surgery and is going to be catheterized, we could try to determine whether the patient is carrying the bacteria and cure that person of it before the surgery. Ideally, that would reduce the chances of developing one of these life-threatening infections.”
Feldman is co-senior author of the team’s published paper, which is titled “Catheterization of mice triggers resurgent urinary tract infection seeded by a bladder reservoir of Acinetobacter Baumannii,” in which the authors concluded, “Our findings could, in the future, potentially lead to the implementation of new preemptive strategies to mitigate the risk of A. baumannii infections and subsequent hospital outbreaks.”
Hospitals have strict hygiene and sanitation protocols to protect patients from bacteria that rarely sicken healthy people but can be deadly for vulnerable patients already hospitalized with serious illnesses. Nearly 100,000 people die every year in U.S. hospitals of infections they develop after being admitted. But despite intense infection-control efforts, new strains of bacteria keep on emerging, seemingly out of nowhere, to infect people in hospitals worldwide.
“Health care–associated infections are often associated with the use of medical devices such as catheters and ventilators, surgical procedures, transmission between patients and health care workers, and overuse of antibiotics,” the authors explained, citing WHO figures indicating that the direct cost of healthcare-associated infections to hospitals is at least $35.7 billion in the United States. “Annually, about two million patients suffer from health care–associated infections, and nearly 100,000 patients are estimated to die in the United States,” the authors further wrote.
A. baumannii is a major threat to hospitalized people, causing many cases of UTIs in patients with urinary catheters (catheter-associated urinary tract infections, CAUTI), pneumonia in people on ventilators, and bloodstream infections in people with central-line catheters into their veins. The bacteria are notoriously resistant to a broad range of antibiotics, so such infections are challenging to treat and easily can turn deadly. “Recently, the frequency of multidrug resistance in A. baumannii has greatly increased, and it is currently the Gram-negative bacterium displaying one of the highest rates of multidrug resistance worldwide,” the investigators stated. “Reflecting its growing impact on global health, the WHO and CDC have classified this bacterial species as an urgent, high-priority threat in need of new therapeutics.”
For the newly reported study, Feldman teamed up with co-senior author Scott J. Hultgren, PhD, the Helen L. Stoever professor of molecular microbiology and an expert on UTIs, to investigate why so many A. baumannii UTIs develop after people receive catheters. Most UTIs among otherwise healthy people are caused by the bacterium Escherichia coli. Research has shown that E. coli can hide out in bladder cells for months after a UTI seems to have been cured, and then re-emerge to cause another infection.
Feldman and Hultgren—along with co-first authors Jennie E. Hazen, a graduate student, and Gisela Di Venanzio, PhD, an instructor in molecular microbiology—investigated whether A. baumannii can, similarly to E. coli, hide inside cells. They studied mice that had experienced a UTI caused by A. baumannii infection. The mice also had weakened immune systems because, like people, healthy mice can fight off A. baumannii. Once the initial infections in the test mice had resolved and no bacteria were detected in the animals’ urine for two months, the researchers inserted catheters into the mice’s urinary tracts, using a sterile technique. They found that within 24 hours, about half of the animals developed UTIs caused by the same strain of A. baumannii that had been responsible for the initial infection.
“The bacteria must have been there all along, hiding inside bladder cells until the catheter was introduced,” Hultgren said. “Catheterization induces inflammation, and inflammation causes the reservoir to activate, and the infection blooms.” The authors further wrote, “Here, using a murine model of infection, we demonstrate that A. baumannii can survive for months in a bladder reservoir within the host and that the insertion of a medical device such as a catheter can trigger a resurgent infection.”
Since A. baumannii rarely causes symptoms in otherwise healthy individuals, many people who carry the bacteria may never know they’re infected, the researchers said. As part of their study, the team searched the scientific literature and discovered that about 2% of healthy people carry A. baumannii in their urine.
“I wouldn’t put much weight on the precise percentage, but I think we can say with certainty that some percentage of the population is walking around with A. baumannii,” Feldman commented. “As long as they’re basically healthy, it doesn’t cause any problems, but once they’re hospitalized, it’s a different matter. “Given that about 2% of the human population may exhibit asymptomatic A. baumannii bacteriuria, we propose that patients can unknowingly enter the clinic already harboring the pathogen, long after an initial colonization event,” the team continued. “We propose that these host reservoirs could, in turn, become activated upon intervention with a medical device such as a catheter, resulting in the triggering of a resurgent infection.”
Feldman further commented, “This changes how we think about infection control. We can start considering how to check if patients already have Acinetobacter before they receive certain types of treatment; how we can get rid of it; and if other bacteria that cause deadly outbreaks in hospitals, such as Klebsiella, hide in the body in the same way. That’s what we’re working on figuring out now.”
The authors also pointed out that while around 20% of A. baumannii clinical isolates are from urinary sources, the most important clinical manifestation of A. baumannii is pneumonia, and ventilator-associated pneumonia is the most common type of infection caused by A. baumannii. Thus, they said, “future experiments will aim to decipher whether resurgent infections can be triggered in the context of the respiratory tract.”