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Texas A&M study reveals how antibiotic use during leukemia treatment reshapes the gut microbiome

Research shows that routine infection prevention during chemotherapy can alter microbial diversity and impact antibiotic resistance.

a portrait of a woman wearing glasses inside a research laboratory.

Dr. Jessica Galloway-Peña studies how antibiotic use during chemotherapy affects the gut microbiome and infection risk.

Credit: Nadya Pichkasova, Texas A&M University College of Veterinary Medicine and Biomedical Sciences

Patients undergoing intensive chemotherapy for acute myeloid leukemia are routinely treated with multiple antibiotics to prevent infection, a practice that new research from Texas A&M University shows can significantly reshape the gut microbiome and influence the risk of antibiotic-resistant infections.

In a study published in the journal Antibiotics, researchers examined how antibiotic use during remission induction chemotherapy — the initial, intensive phase of treatment aimed at eliminating leukemia cells — affected the gut microbiome and the collection of antibiotic resistance genes in patients with acute myeloid leukemia (AML), a fast-growing cancer of the blood and bone marrow.

“Because doctors would rather be safe than sorry, they start treating their patients with antibiotics when they get a fever, even if they don’t have a bacteria-positive culture,” said Dr. Jessica Galloway-Peña, assistant professor in the Texas A&M College of Veterinary Medicine and Biomedical Sciences’ Department of Veterinary Pathobiology. “However, our study shows that antibiotic use during treatment can be refined in ways that protect patients while also limiting unintended effects on the microbiome.”

The research is part of a long-term effort to better understand how chemotherapy alters the microbiome and how these changes impact infection risk and treatment outcomes, said Galloway-Peña, the principal investigator of the study.

“We are trying to convince oncologists and infectious disease doctors to move away from the idea that antibiotics are always harmless,” Galloway-Peña said. “In some cases, they can create problems further down the line.”

A high-risk period for infection

In the United States alone, AML is diagnosed in about 1% of all cancers — or roughly 20,000 to 22,000 people each year — making infection risk in this population a significant clinical concern.

Patients with AML face an elevated risk of infection because chemotherapy suppresses immune function and damages the lining of the gastrointestinal tract, allowing bacteria that normally live in the gut to escape into the bloodstream.

“The bacteria are thought to get out of the gut and translocate into the bloodstream,” Galloway-Peña said. “These patients are not only at risk for infections from outside sources but also from organisms that already live within their own bodies.”

According to Galloway-Peña, patients undergoing remission induction chemotherapy can receive, on average, about six different antibiotics during their initial inpatient treatment, which often lasts about four weeks.

“Instead of potentially helping you, empirical antibiotic treatment can actually increase your risk,” she said, referring to the risk of antibiotic-resistant infections later. “We kill off the good bacteria that keep resistant organisms in check, and we end up selecting for antibiotic-resistant organisms that are already present in the gut.”

Antibiotic exposure and unexpected patterns

The study also analyzed antibiotic administration alongside data from the microbiome and resistome — the comprehensive collection of all antibiotic resistance genes — to understand how different treatment patterns affected the genetic landscape of the gut.

They found that patients who were treated with a wider variety of antibiotics ended up with fewer kinds of antibiotic-resistance genes than expected.

The team initially expected that exposure to more antibiotics would lead to greater resistance, but that was not the case. According to Galloway-Peña, reducing the diversity of bacteria in the gut also reduces “the number of possible combinations,” which may limit how easily antibiotic resistance genes are transferred.

Linezolid stands out

Linezolid, a powerful antibiotic used to treat certain serious bacterial infections, including MRSA, is commonly used in patients with AML to treat suspected or confirmed gram-positive infections, particularly during prolonged hospital stays when patients are highly vulnerable to infection.

Linezolid is often prescribed for several days or longer during inpatient treatment, depending on infection risk and clinical response.

The study found that increased exposure to linezolid was associated with a greater loss of microbiome diversity. Previous research has shown that this loss can make it easier for harmful bacteria to take hold and cause infection.

At the same time, longer linezolid use was associated with a reduced risk of colonization by antibiotic-resistant organisms. Colonization occurs when antibiotic-resistant bacteria live on or in the body without causing immediate symptoms.

“Each additional day of linezolid basically reduces your risk of antibiotic-resistant colonization,” Galloway-Peña said.

These findings help clarify the relationship between microbiome disruption and antibiotic-resistant infections, showing that the two are not always directly linked.

“Even though the loss of diversity is associated with infection, it doesn’t necessarily mean that it’s associated with antibiotic-resistant infection,” Galloway-Peña said. “You have to keep those two concepts separate.”

Looking ahead

Future research will focus on using genomic and microbiome data to guide more personalized antibiotic treatment strategies, with the goal of better tailoring care to individual patients.

“Not all treatment is one size fits all,” she said. “With the advances of medicine, we could definitely get to a point to where we can personalize therapy based on somebody’s own microbiome.”

More information: Characterization of Antibiotic Administration Factors Associated with Microbiome Disruption and Subsequent Antibiotic-Resistant Infection and Colonization Events in Acute Myeloid Leukemia Patients Receiving Chemotherapy
DOI: 10.3390/antibiotics14080770
https://www.mdpi.com/2079-6382/14/8/770

Journal: Antibiotics