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Infectious medicine, virology

Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy

Leukemia volume 34, pages 312–316 (2020)Cite this article

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Up to half of patients with solid tumors and >80% of those with hematologic malignancies develop a fever during chemotherapy-induced neutropenia [1]. Current practice includes antibacterial prophylaxis with escalation to broader-spectrum antibiotics at the onset of neutropenic fever (NF). However, because microbiological workup remains negative in most NFs [2], this practice represents an empiric antimicrobial attack rather than a mechanistic approach inspired by precisely defined pathogenesis. The fear of failing to diagnose and adequately treat a catastrophic infection in the immunocompromised patient has resulted in heavy antibiotic exposure during the period of neutropenia. Unfortunately, this approach has led to serious adverse consequences, including increased antibiotic resistance and Clostridium difficile infection. Thus, there is an urgent need to re-evaluate the prevailing antimicrobial paradigm.

Bloodstream infection (BSI) accounts for 10–25% of all NFs [2]. Cytotoxic therapy impairs gut barrier integrity, facilitating bacterial translocation and increasing the risk of BSI [3]. In addition, antibiotics disrupt the gut microbiota, which normally prevents pathogen colonization [4], provides tonic stimulation to the gut barrier [5], and facilitates recovery from chemotherapy-induced injury. Therefore, it is likely that iatrogenic damage to the microbiota contributes to BSI and NF during chemotherapy. Using serum flagellin as a culture-independent surrogate for motile bacteremia, we demonstrate that specific changes in the indigenous gut microbiota precede BSI.

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Acknowledgements

AR was supported by grants from the University of Minnesota (Medical School Innovation award and Foundation grant for new faculty) and a Marrow on the Move grant from the Division of Hematology, Oncology, and Transplantation. In addition, funding from Achieving Cures Together and Hubbard Broadcasting Foundation supported this research. We thank Markas Welke, Andrea Hoeschen, and Kevin Olson for coordinating sample collections. Sequence data were processed and analyzed using the resources of the Minnesota Supercomputing Institute.

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Authors and Affiliations

  1. Division of Hematology, Oncology, and Transplantation, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    Armin Rashidi, Shernan G. Holtan & Daniel J. Weisdorf

  2. Department of Surgery, University of Minnesota, Minneapolis, MN, 55455, USA

    Thomas Kaiser & Christopher Staley

  3. BioTechnology Institute, University of Minnesota, St. Paul, MN, 55108, USA

    Thomas Kaiser, Alexander Khoruts & Christopher Staley

  4. Division of Gastroenterology, Hepatology, and Nutrition, Department of Medicine, University of Minnesota, Minneapolis, MN, 55455, USA

    Carolyn Graiziger, Tauseef Ur Rehman & Alexander Khoruts

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  1. Armin Rashidi
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Correspondence to Armin Rashidi.

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Rashidi, A., Kaiser, T., Graiziger, C. et al. Specific gut microbiota changes heralding bloodstream infection and neutropenic fever during intensive chemotherapy. Leukemia 34, 312–316 (2020). https://doi.org/10.1038/s41375-019-0547-0

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