Scientists have used genome sequencing to find out how far a drug-resistant gastrointestinal bacterium can spread within a hospital and to highlight the challenge hospitals face in controlling infection.
Enterococcus faecium is a bacterium that is commonly found in the gastrointestinal tract and usually resides there without causing the host’s problems. However, a potentially life-threatening infection can occur in immunocompromised patients.
Over the past three decades, strains have emerged that are resistant to front-line antibiotics like ampicillin and vancomycin, which limits treatment options – and of particular concern is that these strains are common in hospital-acquired E. faecium infections.
A team of scientists at Cambridge University and the London School of Hygiene and Tropical Medicine has developed an approach that combines epidemiological and genomic information to capture the spread of bacteria in healthcare. This has helped hospitals identify sources of infection and provide information about infection control measures.
In a study published today in Natural microbiologyThe team applied this technique to the spread of drug-resistant E. faecium in a hospital.
“We have known for over two decades that hospital patients can catch and spread drug-resistant E. faecium. To prevent it from spreading, we need to understand where the bacteria live – their ‘reservoirs’ – and how they are transmitted.
Most previous studies have relied on the cultivation of bacteria from samples. But as we have shown, sequencing the entire genome – with a view to the DNA of the bacteria – combined with detailed patient and environmental samples can be a powerful tool for documenting the spread and showing ways to prevent further outbreaks. ”
Dr. Theodore Gouliouris, Study Author, First Author, Department of Medicine, Cambridge University
The team tracked 149 hematology patients admitted to Addenbrooke’s Hospital under the NHS Foundation Trust of Cambridge University Hospitals over a six-month period. They took stool samples from the patients and swabs from the hospital setting and cultured them for E. faecium.
Genomic analysis of the bacteria was much more effective in identifying hospital-acquired E. faecium: out of 101 patients who could be tracked, genomic analysis found that two-thirds of patients acquired E. faecium, compared with less than half using culture methods alone .
Almost half (48%) of the swabs taken from the hospital were positive for vancomycin-resistant E. faecium. This comprised 36% of the medical devices, 76% of the non-contact areas such as ventilation slots, 41% of the sleeping places and 68% of the shared bathrooms tested.
The researchers showed that even a thorough cleaning couldn’t eradicate the bacteria. The hospital performed a thorough cleaning on one ward over a three-day period during the study when patients were moved to another location. However, when the team examined locations before the patients returned to the ward, they found that 9% of the samples still tested positive for the bacteria. Within three days of the patients returning to the ward, around half of the sites examined tested positive.
Three quarters (74%) of the patients (111/149) were carriers of the A1 clade – a multi-resistant E. faecium strain that is common in hospitals and is resistant to the antibiotic ampicillin and often develops resistance to vancomycin. Of these 111 patients, 67 had strong epidemiological and genomic links to at least one other patient and / or their immediate environment.
“The fact that these cases were all linked to another patient or their environment strongly suggests that they had taken the multidrug-resistant bacteria into the hospital,” said Dr. Author Francesc Coll of the London School of Hygiene and Tropical Medicine.
Further genomic analyzes showed that there were several subtypes (defined by their genetic similarity) within this multi-resistant strain. However, it was not uncommon for a patient to carry more than one subtype, which – without detailed genome analysis – could distort attempts to identify the transmission route of an infection.
Notably, despite the prevalence of up to 115 subtypes, 28% of E. faecium acquisitions were caused by only two over-widespread subtypes. The authors found no evidence of resistance or tolerance to common disinfectants to explain the success of these subtypes.
Six study patients developed an “invasive infection,” which meant that they carried E. faecium asymptomatically in their intestines, but subsequently developed a symptomatic infection. When comparing the genomes of the infection and intestinal strains, the authors found that invasive E. faecium infections originated from the patient’s own intestines.
“Our study builds on previous observations that drug-resistant E. faecium strains can persist in the hospital environment despite standard cleaning. Nevertheless, we were surprised at how short-lived the effect of the deep cleansing was, ”added Dr. Gouliouris added.
“Despite the use of cleaning agents and procedures that have proven effective against the bug, we have found a high level of E. faecium adapted for hospitals. This shows how difficult it can be to control outbreaks in hospitals. ”
Senior author Professor Sharon Peacock of the Department of Medicine at the University of Cambridge added, “The high rates of infection with drug-resistant E. faecium in certain vulnerable patient populations and its ability to bypass cleaning measures are an important challenge for infection control.”
“Containing this global epidemic will require patient screening, adequate isolation and dedicated toilet facilities, improved and more frequent cleaning procedures, and more stringent hygiene practices for healthcare workers.
“But it is also a sign of how urgently we need to tackle the inappropriateness of antibiotics around the world, which is widely recognized as a catastrophic threat to our health and our ability to control infections.”
T. Gouliouris et al. (2020) Quantifying Enterococcus faecium Acquisition and Transmission Using Genomic Surveillance. Natural microbiology. doi.org/10.1038/s41564-020-00806-7.
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