Antibiotic resistance is often spread in the gut microbiota of hospitalized people

A targeted decontamination could be a strategy to control the spreading of carbapenem-resistance plasmids both amoung patients and within patients.
Table of Contents

• Resistance transfer
• Transfer hotspots

What is already known on this topic
Bacteria that are resistant to the carbapenem group of antibiotics — also known as carbapenemase-producing enterobacteriaceae (CPE) — are being increasingly found in clinical settings. CPE typically carry circular molecules of DNA called plasmids that harbor genes conferring resistance against carbapenem antibiotics. CPE can spread from patient to patient in hospitals, or they can transfer their resistance plasmids to resident bacteria in the gut microbiota of patients. However, the contribution of each of these process to the overall spread of carbapenem resistance in hospitals is poorly understood.

What this research adds
Over two years, researchers analyzed epidemiological data from more than 9,000 patients and combined them with genome information from 250 enterobacteria. Bacteria carrying carbapenem-resistance plasmids, such as Klebsiella pneumoniae and Escherichia coli, were often spread between individuals in specific hospital wards. The researchers also found evidence of the transfer of carbapenem-resistance plasmids between bacteria within the same person.

Conclusion

The findings could help to develop new strategies to control the spread of carbapenem-resistant bacteria within hospitals.

Antibiotic resistant bacteria, which are able to survive and even proliferate in the presence of an antibiotic, are one of the biggest threats to global health. New research shows that antibiotic resistance is often spread between bacteria in the gut of hospitalized people.

The findings, published in Nature Microbiology, could help to develop new strategies to control the spread of antibiotic resistance within hospitals.

Carbapenemase-producing enterobacteriaceae (CPE) — bacteria that are resistant to the carbapenem group of antibiotics — are being increasingly found in clinical settings. CPE typically carry circular molecules of DNA called plasmids that harbor genes conferring resistance against carbapenem antibiotics. Unlike chromosomal DNA, which is only transmitted from mother to daughter cells, plasmids can be transmitted between unrelated bacteria, giving microbes resistance to one or more antibiotics.

Scientists have known that CPE can spread from patient to patient in hospitals, or they can transfer their resistance plasmids to resident bacteria in the gut microbiota of patients. However, the contribution of each of these process to the overall spread of carbapenem resistance in hospitals is poorly understood, the researchers say.

To identify the spread routes of a carbapenem-resistance plasmid in a hospital setting, Álvaro San Millán at the Hospital Universitario Ramón y Cajal and his colleagues analyzed epidemiological data from more than 9,000 patients over a period of two years. Then, the team combined these data with genome sequence information from 250 enterobacteria.

Resistance transfer

From March 2014 to March 2016, the researchers collected more than 28,000 rectal swabs from 9,275 patients, and they isolated 171 enterobacteria strains carrying carbapenem-resistance plasmids from 105 patients. Klebsiella pneumoniae was the microbe that carried resistance plasmids most frequently. However, the team detected resistance plasmids in other enterobacterial species, including Escherichia coli.

In several individuals who carried bacteria with carbapenem-resistance plasmids, the researchers observed a co-colonization of the gut microbiota with more than one bacterial species carrying the plasmid. This suggests that carbapenem-resistance plasmids are transferred between bacteria within the same person, the authors say.

Genetic analyses of the plasmids confirmed a pervasive transfer between bacteria within the same patient, the researchers say.

Transfer hotspots

Next, the team analyzed the spread of the most frequent K. pneumoniae and E. coli resistance-carrying strains within four hospital wards. K. pneumoniae strains carrying carbapenem-resistance plasmids were transmitted within every ward and even between wards, with neurosurgery being the ward with the highest frequency of transmission of the resistant strains.

The neurosurgery ward included 11 rooms with 20 beds, and of the 16 patients colonized with K. pneumoniae carbapenem-resistant strains, six had stayed in the same room. This suggests that the room acted as a hotspot for K. pneumoniae colonization and transmission, the researchers say.

Transmission events of other K. pneumoniae carbapenem-resistant strains were found in the pneumology and the gastroenterology wards, and another one between the gastroenterology and urology wards. Similarly, between-patient transfers of a carbapenem-resistant strain of E. coli were identified in the gastroenterology ward and between the gastroenterology and urology wards.

The findings could help to design interventions to control the spread of carbapenem-resistance plasmids both between patients, by detecting transfer hotspots, and within patients, by clearing the plasmids from the patients’ gut microbiota through targeted decontamination.