NEW YORK (GenomeWeb) – In a large-scale yearlong microbiome project, researchers at the University of Chicago and their collaborators have documented how bacteria colonize a newly opened hospital and spread back and forth between patients, staff members, and surfaces.
The study, published in Science Translational Medicine today, provides a detailed map of the flow of bacteria within a hospital environment and serves as a foundation for future studies of the transmission of hospital-acquired infections.
"We now have a roadmap of the hospital environment and are able to generate specific interventional hypotheses for future work," said Jack Gilbert, senior author of the study and director of the Microbiome Center as well as a professor of surgery at the University of Chicago.
While the study found plenty of bacteria on hospital surfaces, despite rigorous cleaning, those microbes were mostly benign. "It was not like the hospital was riddled with superbugs," Gilbert said. "We hear about that so much, we assume when we go into a hospital, there are just tons of killer organisms around. We just were not able to find any evidence of that at all."
His group had previously analyzed microbial communities in homes and offices to try and understand how bacteria move between people and surfaces, and how they evolve under selection pressure, and the opening of a new hospital provided them with an opportunity to do this in a healthcare environment.
For their study, the researchers analyzed samples taken at the Center for Care and Discovery, a new hospital that is part of the University of Chicago, during the two months before it opened in February 2013 and for 10 months afterwards.
Samples came from 10 patient rooms and two nursing stations on two floors, one caring for surgical patients and one for cancer patients. One patient room on each floor was sampled daily, the others weekly. All patient rooms were cleaned on a daily basis and more stringently after patients were discharged.
The researchers analyzed more than 6,500 microbial samples in total. In patient rooms, they swabbed bedrails, floors, faucet handles, and gloves, while samples from the nurse stations came from chair armrests, faucets, computer mice, countertops, floors, and phones. Patient skin swabs were taken from their hands, nose, armpit, and, initially, the groin area, and hospital staff had their hands, nose, cell phone, pager, shirt hem, and shoes sampled. In addition, tap water and air filter samples were analyzed.
Samples were frozen and sent to Argonne National Laboratory for sequencing analysis. For most, the scientists amplified the V4 region of the 16S rRNA gene and sequenced the amplicons using Illumina HiSeq 2000 and MiSeq machines. In addition, 92 samples were analyzed by shotgun metagenomic sequencing, using the Illumina HiSeq.
As soon as the hospital opened and patients and staff moved in, bacteria associated with human skin, such as Corynebacterium, Staphylococcus, and Streptococcus, started to replace species on surfaces that had dominated prior to that, such as Acinetobacter and Pseudomonas.
Also, when patients first arrived, they acquired microbes present on surfaces in their room. Despite extensive cleaning between patients, there are always residual microbes lingering around, and it is technically impossible to sterilize the environment, Gilbert explained. However, he said, none of the events where patients picked up microbes from their room were linked to adverse health outcomes.
However, after a day, bacteria tended to move in the other direction, from patients' skin to the room, indicating that their microbiome was taking over and that bacteria from the room "were not competitive on the patient's skin, so they were eradicated," he said.
The researchers also found that staff members, who usually wore gloves or a mask when they entered patient rooms, transferred more of their microbes to patients, who did not wear any protective gear, than patients transferred to them, but again, this did not have any adverse health outcomes.
Clinical factors, such as whether patients were receiving chemotherapy, antibiotics, or were recovering from surgery, did not appear to have a big impact on the diversity of bacteria on patients' skin.
Interestingly, during the summer months, when humidity was higher, staff members had more similar microbiomes than in the winter, suggesting that they exchanged microbes more frequently during that time.
The metagenomic analysis of samples collected from the same hospital rooms over several months revealed the presence of antibiotic resistance genes over time, which was almost always greater on room surfaces than on skin. Antibiotic resistance was most often associated with Staphylococcus aureus, Staphylococcus epidermidis, and Corynebacterium striatum for skin samples, and with Escherichia coli and Pseudomonas aeruginosa for surface samples.
Gilbert said that the increase in antibiotic resistance might result from general selection pressure. Preliminary data, which the paper did not report, suggest that the hospital environment is a more stressful ecosystem for many microorganisms because it is so stringently cleaned, he said, which favors stress-resilient strains. Such stress resilience could be the ability to colonize skin more effectively, resistance to antibiotics, or tolerance to factors like drought. However, he said, further testing is needed to determine whether selection is linked to increased disease levels.
Another interesting point the researchers did not report, he said, is that they did not find any correlation between the degree of microbial exchange between patients and their environment and their likelihood of acquiring a hospital-associated infection. "We had a few patients with hospital-associated infections, but those patients were not sharing more microbes with their environment, there was not an increased degree of traffic," Gilbert said.
Hospital-associated infections, he said, may be due to "incredibly rare sporadic events" that the study was unable to catch because it did not track patients' microbiomes around the clock.
His team is now planning a follow-up study with a group from the Centers for Disease Control and Prevention where they will closely monitor the movements of every single person in a hospital room and how they interact with surfaces. They idea is to study "whether any of the organisms which [patients] acquire have any relationship to disease burden or adverse or positive health outcomes during their hospital stay," he said. "But we need a greater degree of resolution to be able to pinpoint events that could be challenging a healthcare environment."
While the Chicago hospital project may not have an immediate clinical impact, it lays the groundwork for future similar studies and provides new ideas for infection control. "Now we know that people are exchanging microbes with their environment constantly – it's a bidirectional superhighway, almost," Gilbert said, and it may never be possible to control all sources of organisms patients may come into contact with.
One idea that has come out of the study, he said, is to strengthen the resilience of patients to pathogens by making their skin or intestinal system less stressful to bacteria. Animal research, for example, has shown that surgery can activate immune pathways that make the animals' gastrointestinal tract less hospitable to microbes, which in turn activates their virulence, he said.
Interventions that reduce the amount of stress microbes experience may be able to counteract this. "Maybe we can get to the point where we use probiotic formulations, either through consumption, or on the skin, or maybe even in the environment of the hospital, to reduce the likelihood that a virulent organism will activate a disease pathways in those environments," Gilbert said. "We're not there yet but getting very close."