Gut bacteria surveillance may blunt deadly infections in leukemia transplant patients

For patients with acute leukemia, the road to a bone marrow transplant is long, punishing, and punctuated by hospital stays that can quietly reshape the microbial landscape of the gut. A new study from Verona University Hospital in Italy suggests that keeping close watch on that landscape may matter more than clinicians once thought. Researchers followed 100 adults with acute myeloid or lymphoblastic leukemia from the moment of diagnosis through allogeneic hematopoietic stem cell transplantation, a procedure in which donor stem cells are infused to rebuild the patient’s blood and immune system after intensive chemotherapy. Their findings, published in Frontiers in Cellular and Infection Microbiology, offer a nuanced answer to one of the most debated questions in transplant medicine: does carrying multidrug-resistant organisms in the gut doom these patients, or can careful surveillance and targeted antibiotics tame the threat?

The answer, according to the team led by hematologist Cristina Tecchio, is a qualified no. Rectal colonization with multidrug-resistant organisms, or MDROs, was detected in 35 percent of the transplant recipients, yet not a single patient died of an MDRO-related infection within the first 100 days after transplantation. That zero infection-related mortality is striking, because gut colonization with resistant bacteria has repeatedly been linked in other studies to deadly bloodstream infections and poorer survival in transplant recipients. The Verona data suggest that the danger is real but manageable, provided clinicians know who is carrying what and act on that knowledge quickly.

The study was retrospective and longitudinal, reviewing hospital records of patients transplanted at the Verona hematology unit between April 2019 and April 2025. All patients were screened for MDROs by rectal swab at hospital admission and weekly during every hospitalization, from induction chemotherapy onward. The microbiology behind the screening is technically demanding: swabs were streaked onto selective media designed to flush out extended-spectrum beta-lactamase-producing Enterobacterales, carbapenemase-producing strains, and vancomycin-resistant enterococci. Carbapenemase production was confirmed with rapid biochemical tests, and enzyme types were identified with an immuno-chromatographic assay detecting NDM, OXA-48, KPC, VIM, and IMP-like carbapenemases. Clonality was assessed with an infrared spectroscopy system that clusters bacterial isolates by their spectral fingerprints, allowing the team to determine whether bacteria recovered months apart were the same strain.

That technical rigor paid off in an unexpected discovery. Of the 44 MDRO strains detected across the cohort, 70.5 percent had already been isolated in the same patients during previous hospital stays for induction or consolidation chemotherapy. In other words, most of the resistant bacteria found around the time of transplant were not new arrivals; they were old tenants that had persisted through weeks of treatment, sometimes disappearing from screening only to reappear during the profound neutropenia that follows the conditioning regimen. The researchers confirmed this persistence in two patients using clonality analysis and PCR, which detected the same ESBL resistance genes, blaCTX-M1 in one case and blaSHV in the other, in isolates recovered before and after transplantation.

This finding carries a sober clinical implication: a single negative rectal swab does not reliably mean the gut has been cleared. Negative results may reflect intermittent carriage, bacterial loads below the detection threshold of culture-based screening, sampling variability, or temporary suppression of the colonizing population by antibiotics. The Verona team argues that a patient’s longitudinal microbiological history, including the species, resistance phenotype, and date of every prior isolation, may be more informative than the most recent screening result. They call for that information to be systematically transferred between referring hematology units and transplant centers and incorporated into pre-transplant risk assessment.

The epidemiology of colonization itself was revealing. Enterobacterales, a family of Gram-negative gut bacteria that includes Escherichia coli and Klebsiella pneumoniae, accounted for 72.7 percent of all MDROs, mostly ESBL-producing strains. Nearly half of colonized patients, 45.7 percent, were already positive at hospital admission for the transplant, while the rest became positive during hospitalization, within 33 days after the infusion. Notably, four patients colonized with ESBL-producing E. coli or K. pneumoniae later shifted their resistance patterns, acquiring carbapenem resistance, a change that narrows treatment options considerably. The researchers acknowledge that routine fluoroquinolone prophylaxis, given until neutrophil engraftment, may have exerted selective pressure on the intestinal microbiota, favoring the persistence and expansion of resistant Enterobacterales.

Colonization did translate into more infections, even if those infections proved survivable. Bloodstream infections caused by MDROs occurred in 20 percent of carriers compared with only 3.1 percent of non-carriers, a statistically significant difference, and MDRO-related urinary tract infections occurred in 20 percent of carriers versus 6 percent of non-carriers. Seven of the nine patients who developed MDRO-related bloodstream infections were rectal carriers, underscoring the gut as the likely reservoir. Yet none of these infections was life-threatening, no patient required intensive care, and there were no carbapenem-resistant bloodstream infections at all. The team attributes this tempered severity to targeted empirical antibiotics: when fever struck, colonized patients were treated according to their known resistance profiles rather than with a one-size-fits-all regimen, and therapy was continued for at least 14 days after an MDRO-related bloodstream infection, withdrawn only after two consecutive negative blood cultures.

Survival analysis told a subtler story. Overall survival was significantly lower in MDRO carriers at univariate analysis, with estimated survival of 53.4 percent versus 80.6 percent beyond 24 months, and carriers had 2.37 times the risk of death compared with non-carriers. But when the researchers adjusted for disease status in a multivariable Cox model, the association between colonization and survival dissolved, with only active disease at transplant, which carried a 5.11-fold higher hazard of death, remaining significant. Transplant-related mortality showed a similar pattern, a trend toward significance at univariate analysis that vanished after adjustment. The interpretation offered by the authors is that MDRO colonization may primarily reflect cumulative healthcare exposure, repeated antimicrobial pressure, and greater underlying disease and treatment complexity, rather than acting as an independent determinant of mortality.

The study has clear limitations that the authors confront directly. It was retrospective, single-center, and relatively small, with few outcome events, rendering the multivariable analyses exploratory and potentially underpowered. Clonality of recurrent strains could be confirmed in only two cases. The center’s bundle of supportive practices, including weekly surveillance, standardized prophylaxis, protective isolation, and a low-microbial diet, was implemented as routine care and not evaluated independently, so its individual contribution to the favorable outcomes cannot be isolated. Multicenter studies with larger cohorts are needed to validate the findings.

Even so, the message resonates at a time when antimicrobial resistance is climbing worldwide and transplant medicine is expanding. The Verona results suggest that the prognostic weight of gut MDRO colonization in acute leukemia transplant recipients is not fixed; it can be lightened by systematic surveillance that extends beyond admission screening, by awareness of each patient’s past colonization history, and by the prompt use of targeted antibiotics followed by rapid de-escalation when cultures come back negative. In a field where conflicting studies have left clinicians uncertain about how much to fear resistant gut bacteria, this Italian cohort offers a pragmatic middle path: the bacteria are common, the infections are more frequent in carriers, but with vigilance and tailored therapy, the deadliest outcomes may be preventable.

Subject of Research: Infectious Diseases

Article Title: Rectal colonization with multidrug-resistant organisms in adult acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective, longitudinal, single-center study

Article References: Tamellini, E., Bonetto, C., Mazzariol, A., Mazzaferri, F., Diani, E., Tolio, F., Pagnin, S., Vatteroni, A., Crema, A., Schena, A., & Tecchio, C. (2026). Rectal colonization with multidrug-resistant organisms in adult acute leukemia patients undergoing allogeneic hematopoietic stem cell transplantation: a retrospective, longitudinal, single-center study. Frontiers in Cellular and Infection Microbiology, 16, Article 1902132. https://doi.org/10.3389/fcimb.2026.1902132

Image Credits: AI Generated

DOI: 10.3389/fcimb.2026.1902132

Keywords: multidrug-resistant organisms, stem cell transplantation, acute leukemia, antimicrobial resistance, bloodstream infection, rectal colonization, infection surveillance, Rectal, colonization, multidrug-resistant, organisms, adult