The first evidence: drug-resistant bacteria can spread from the gut to the lungs

A new study published by the University of Oxford during World Antimicrobial Awareness Week has important findings
on the emergence and persistence of antimicrobial resistance (AMR).
The findings, published today in the journal Nature Communications, provide the first direct evidence
that AMR bacteria migrate from a patient's gut microbiota to the lungs, increasing the risk of deadly infections.

The team, led by the University of Oxford's Department of Biology, said applying the findings could save lives because it highlighted the importance of preventing pathogenic bacteria from moving from the gut to other organs, which can lead to serious infections
.

The study was conducted
on a patient carrying Pseudomonas aeruginosa as part of the gut microbiome.
The bacteria are one of the leading causes of nosocomial infections and are particularly good at fighting antibiotics
.
When Pseudomonas is embedded in healthy intestinal flora, it is not usually considered dangerous, but it can cause serious infections
in the lungs of hospitalized patients.

During hospitalization, patients are treated
with the antibiotic meropenem for suspected urinary tract infection (UTI).
Meropenem treatment resulted in the killing of non-resistant bacteria in the gut and lungs, and the growth and proliferation of antibiotic-resistant Pseudomonas mutants
.
It was then discovered that Pseudomonas transferred from the intestine to the patient's lungs during antibiotic treatment, where it evolved higher levels of
antibiotic resistance.

"Hospital-acquired infections are one of the biggest burdens of
antibiotic resistance.
Our research shows that pathogenic bacteria from a patient's own gut flora can spread to the lungs, where they can cause infections
that are difficult to treat.
These findings highlight the importance of clearing AMR bacteria from the intestinal flora of hospitalized patients, even if they do not cause infection," said
Professor Craig MacLean from the Department of Biology.

As antibiotic resistance comes under increasing attention in hospitals, preventing the spread of antibiotic-resistant bacteria to other vital organs, such as the lungs, is critical
for vulnerable patients.
However, the source of the bacteria that cause these serious infections is difficult to determine
.
The study shows how the gut microbiota acts as a reservoir for antimicrobial-resistant pathogens that can move to the lungs, where they have the potential to cause life-threatening diseases
such as pneumonia.

The results of this study suggest that eliminating AMR pathogens from the gut microbiota of hospitalized patients can help prevent serious infections, and it highlights how antibiotic use can have a profound impact
on bacteria beyond the actual targets of antibiotic treatment.

The researchers tested patients during their hospital stay to track how long
they were infected with Pseudomonas.
Using a genetic method, they built a time-calibrated bacterial family tree that allowed them to analyze the progression and location of the infection, in addition to its evolution
.
They also found a high degree of genetic diversity in the gut, which also suggests that the microbiome may be a reservoir
for drug resistance.

Fortunately, the patient in this case developed an immune response to AMR bacteria in the lungs, preventing the infection from causing pneumonia
.
However, many people in critical situations, especially during the winter months, have weakened immune systems, which means the body is less
able to fight off disease.
Antibiotic resistance policies often focus on reducing infections from outside, but it is also critical
to understand how antibiotic resistance develops and spreads in patients.

The researchers now intend to assess how often
bacterial metastasis from the gut to the lungs occurs in susceptible patients by collecting samples from a larger cohort.

Professor Craig MacLean (Department of Biology), lead author of the study, said: "There is a clear need to develop new approaches to address the challenges
posed by antimicrobial resistance.
Our study shows how gut-lung translocation and antibiotic use combine to drive the spread
of antibiotic resistance in individual patients.
Such insights
are needed to develop new interventions to prevent drug-resistant infections.
For example, our study highlights the potential benefit of eliminating AMR bacteria such as Pseudomonas aeruginosa from the intestinal flora of hospitalized patients, even if these bacteria do not actually cause infection
.
”