A new study of drug-resistant bacteria moving freely between organs could save lives

Oxford University has published a critical new study about what causes antimicrobial resistance (AMR) and what it does. The results, which were published in Nature Communications, show for the first time that AMR bacteria can move from a patient's gut microbiome to their lungs, increasing the risk of infections that can kill them.

The research team, led by the Department of Biology at Oxford University, claims that putting these findings into practice could save lives since it emphasizes the significance of preventing dangerous bacteria from spreading from the gut to other organs where they can cause fatal illnesses.

The Pseudomonas aeruginosa bacterium was found in the patient's gut microbiome during the investigation. One of the most common germs to infect patients in hospitals is this species, which is also highly resistant to antibiotics.

Most people don't think of Pseudomonas as dangerous when it's part of a healthy gut microbiome, but it can cause infections in hospitalized patients' lungs that can kill them.

During their stay in the hospital, the study's patient was given the antibiotic meropenem to treat a possible urinary tract infection (UTI). After being treated with meropenem, non-resistant bacteria in the gut and lungs were killed. This made it possible for antibiotic-resistant Pseudomonas to grow and spread.

Then, the study found that, during antibiotic therapy, Pseudomonas translocated from the gut to the patient's lungs, developing even higher levels of drug resistance.

"Hospital-acquired infections are one of the biggest burdens of AMR. Our work shows that pathogenic bacteria from a patient's gut microbiome can disseminate to the lung, where they may cause difficult-to-treat infections. These findings underscore the importance of eliminating AMR bacteria from the gut microbiome of hospitalized patients, even when they are not causing infection," explained Professor Craig MacLean, Department of Biology.

The study findings could prove important for disease control in hospitals

AMR is becoming a bigger problem in hospitals. Therefore, it's crucial for patients who are already at risk to stop the germs from spreading to other crucial organs like the lung. It can be challenging to pinpoint the source of the bacteria that cause these dangerous illnesses, though.

This work demonstrates how the gut microbiome might serve as a reservoir for AMR infections that can move to the lungs and potentially cause deadly diseases like pneumonia.

The results of this study show that antibiotic use can have significant effects on bacteria that aren't the real targets of antibiotic treatment. The researchers also think that getting rid of AMR pathogens from the gut microbiome of hospitalized patients could help stop serious infections.

To gauge how long the patient had been infected with Pseudomonas, researchers examined them periodically while in the hospital. By building a time-calibrated bacterial family tree, they could look at how the infection changed over time, how it spread, and where it was. There was also a lot of genetic diversity in the gut, which supports the idea that the microbiome may be a source of AMR.

The patient, in this case, got a response from their immune system to the AMR bacteria in their lungs, which stopped the infection from becoming pneumonia. However, a reduced immune system is common in persons in dire situations, especially during the winter, making the body less capable of warding off disease.

AMR strategies frequently concentrate on minimizing infection from outside sources, but it's equally essential to comprehend how AMR can arise and spread inside a patient.

By collecting samples from a much larger cohort, the researchers now plan to determine how frequently gut-to-lung bacterial translocation occurs in susceptible patients.

Lead author of the study Professor Craig MacLean (Department of Biology), said: "There is a clear need to develop new approaches to the challenges that antimicrobial resistance presents. Our study shows how gut-lung translocation and antibiotic use can combine to drive the spread of AMR within a single patient. Insights like this are needed to develop new interventions to prevent resistant infections. For example, our study highlights a potential benefit of eliminating AMR bacteria like Pseudomonas aeruginosa from the gut microbiome of hospitalized patients, even when these bacteria are not causing infection."

You can view the study for yourself in the journal Nature Communications.

Study abstract:

"Bacteria have the potential to translocate between sites in the human body, but the dynamics and consequences of within-host bacterial migration remain poorly understood. Here we investigate the link between gut and lung Pseudomonas aeruginosa populations in an intensively sampled ICU patient using a combination of genomics, isolate phenotyping, host immunity profiling, and clinical data. Crucially, we show that lung colonization in the ICU was driven by the translocation of P. aeruginosa from the gut. Meropenem treatment for a suspected urinary tract infection selected for elevated resistance in both the gut and lung. However, resistance was driven by parallel evolution in the gut and lung coupled with organ specific selective pressures, and translocation had only a minor impact on AMR. These findings suggest that reducing intestinal colonization of Pseudomonas may be an effective way to prevent lung infections in critically ill patients."