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Exposure to antibiotics with anaerobic activity before respiratory viral infection is associated with respiratory disease progression after hematopoietic cell transplant

Bone Marrow Transplantation volume 57, pages 1765–1773 (2022)Cite this article

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Abstract

We examined associations between specific antibiotic exposures and progression to lower respiratory tract disease (LRTD) following individual respiratory viral infections (RVIs) after hematopoietic cell transplantation (HCT). We analyzed allogeneic HCT recipients of all ages with their first RVI during the first 100 days post-HCT. For the 21 days before RVI onset, we recorded any receipt of specific groups of antibiotics, and the cumulative sum of the number of antibiotics received for each day (antibiotic-days). We used Cox proportional hazards models to assess the relationship between antibiotic exposure and progression to LRTD. Among 469 patients with RVI, 124 progressed to LRTD. Compared to no antibiotics, use of antibiotics with broad anaerobic activity in the prior 21 days was associated with progression to LRTD after adjusting for age, virus type, hypoalbuminemia, neutropenia, steroid use, and monocytopenia (HR 2.2, 95% CI 1.1–4.1). Greater use of those antibiotics (≥7 antibiotic days) was also associated with LRTD in adjusted models (HR 2.2, 95% CI 1.1–4.3). Results were similar after adjusting for lymphopenia instead of monocytopenia. Antibiotic use is associated with LRTD after RVI across different viruses in HCT recipients. Prospective studies using anaerobe-sparing antibiotics should be explored to assess impact on LRTD in patients undergoing HCT.

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Fig. 1: Cumulative incidence of proven/probable/possible LRTD by tertiles of number of antibiotic-days in the 21 days before RVI, overall and by virus.
Fig. 2: Cumulative incidence of proven/probable/possible LRTD by categories of antibiotic-days for antibiotic-days of antibiotics with broad anaerobic activity in the 21 days before RVI, overall and by virus.
Fig. 3: Model estimates for unadjusted and adjusted associations of antibiotic exposures in the 21 days prior to 1 day before RVI onset with progression to proven/probable/possible LRTD.

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Data availability

Data supporting the findings from this study are available from the corresponding author upon reasonable request.

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Acknowledgements

We thank Chris Davis, Madeline Kesten and Ryan Basom for database services.

Funding

This work was supported by the National Institutes of Health (grant numbers K23AI139385 to CO, R01HL081595 and K24HL093294 to MB, CA18029 to WML [clinical database]); the Fred Hutchinson Cancer Center Vaccine and Infectious Disease Division (biorepository); Seattle Children’s Research Institute Clinical Research Scholars Program Award to CO.

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Author notes

  1. Chikara Ogimi

    Present address: Pediatric Infectious Diseases, National Center for Child Health and Development, Tokyo, Japan

  2. These authors contributed equally: Chikara Ogimi, Elizabeth M. Krantz.

Authors and Affiliations

  1. Pediatric Infectious Diseases Division, Seattle Children’s Hospital, Seattle, WA, USA

    Chikara Ogimi, Alpana Waghmare, Ashley Akramoff, Anthony Mallory & Janet A. Englund

  2. Department of Pediatrics, University of Washington, Seattle, WA, USA

    Chikara Ogimi, Catherine Liu, Alpana Waghmare & Janet A. Englund

  3. Vaccine and Infectious Disease Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Chikara Ogimi, Elizabeth M. Krantz, Jonathan L. Golob, Catherine Liu, Alpana Waghmare, Keith R. Jerome, Steven A. Pergam, David N. Fredricks & Michael Boeckh

  4. Clinical Research Division, Fred Hutchinson Cancer Center, Seattle, WA, USA

    Wendy M. Leisenring, Victor A. Chow, Steven A. Pergam, David N. Fredricks & Michael Boeckh

  5. Department of Laboratory Medicine and Pathology, University of Washington, Seattle, WA, USA

    Keith R. Jerome

  6. Division of Medical Oncology, University of Washington, Seattle, WA, USA

    Victor A. Chow

  7. Department of Medicine, University of Washington, Seattle, WA, USA

    Steven A. Pergam, David N. Fredricks & Michael Boeckh

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Contributions

Authorship contribution: CO designed this study, assisted in analysis, interpreted results, and wrote the manuscript; EMK and WML performed the statistical analysis and wrote the manuscript; JLG, CL, AW, SAP and DNF provided clinical input, interpretation of results, and reviewed the manuscript; KRJ provided technical oversight for laboratory, and reviewed the manuscript; JAE and MB provided oversight, designed this study, interpreted results, and reviewed the manuscript.

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Correspondence to Chikara Ogimi or Michael Boeckh.

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Competing interests

AW reports grant support from Ansun Biopharma, Allovir, VB Tech, Amazon, Inc, GlaxoSmithKline and Pfizer, and is an Advisory Board Member for Kyorin Pharmaceutical. JAE reports grant support from AstraZeneca, Merck, Pfizer, GlaxoSmithKline and Novavax, an Advisory Board Member and consultant for Sanofi Pasteur, Meissa Vaccines, Teva Pharmaceuticals and Astra Zeneca. MB reports grant support from Amazon, GSK, Janssen, Gilead and VirBio, and a consultant for Allovir, Merck, Janssen, Gilead, Kyorin Pharmaceuticals, and VirBio, and an Advisory Board Member for Evrys Bio. All other authors report no potential conflicts. Conflicts that the editors consider relevant to the content of the manuscript have been disclosed.

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Ogimi, C., Krantz, E.M., Golob, J.L. et al. Exposure to antibiotics with anaerobic activity before respiratory viral infection is associated with respiratory disease progression after hematopoietic cell transplant. Bone Marrow Transplant 57, 1765–1773 (2022). https://doi.org/10.1038/s41409-022-01790-8

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