@article{f7ac1913eaae4464b64cf1c5f7915731,
title = "Risk Factors Associated with Severe Clostridioides difficile Infection in Patients with Cancer",
abstract = "Introduction: Antibiotic use is a risk factor for Clostridioides difficile infection (CDI). Few studies have correlated use of prior antibiotic classes with CDI, microbiome composition, and disease severity in patients with cancer. We hypothesized that previous antibiotic exposure and fecal microbiome composition at time of presentation are risk factors for severe CDI in patients with cancer. Methods: This non-interventional, prospective, cohort study examined 200 patients with cancer who had their first episode or first recurrence of CDI. C. difficile was identified using nucleic acid amplification testing. Univariate analysis was used to determine significant risk factors for severe CDI. Fecal microbiome composition was determined by sequencing the V3/V4 region of 16 s rDNA encoding gene. Differential abundance analyses were used to single out significant microbial features which differed across severity levels. Results: On univariate analysis, factors associated with severe CDI included the presence of toxin A/B in stools (odds ratio [OR] 2.14 [1.05–4.36] p = 0.04 and prior 90-day metronidazole use (OR 2.66 [1.09–6.50] p = 0.03). Although alpha and beta diversity was similar between disease severity groups and toxin A/B in stools, increased abundance of Bacteroides uniformis, Ruminococcaceae, and Citrobacter koseri were associated with protection from severe CDI (p < 0.05) and depletion of anaerobes was higher in patients with prior metronidazole exposure. Conclusion: Use of metronidazole for non-CDI indications within 90 days prior to diagnosis and presence of toxin A/B in stools were associated with severe CDI. Findings provide valuable insights into risk factors for severe CDI in an underserved population with cancer that warrants further exploration.",
keywords = "Anaerobes, Cancer, Clostridioides difficile, Metronidazole, Microbiome",
author = "Francisco, {Denise Marie A.} and Liangliang Zhang and Ying Jiang and Adilene Olvera and Javier Adachi and Guevara, {Eduardo Yepez} and Aitken, {Samuel L.} and Garey, {Kevin W.} and Peterson, {Christine B.} and Do, {Kim Anh} and Ryan Dillon and Obi, {Engels N.} and Robert Jenq and Okhuysen, {Pablo C.}",
note = "Funding Information: This work is supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who also funded the journal{\textquoteright}s Rapid Service Fee. Funding Information: We thank the participants of this study. This work is supported by Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA, who also funded the journal{\textquoteright}s Rapid Service Fee. All authors contributed to the study conception and design. Material preparation, data collection and analysis were performed by Denise Marie Francisco, MD, Adilene Olvera, MPH MLS and Eduardo Yepez Guevara, MD. Statistical analysis was performed by Denise Marie Francisco, MD, Liangliang Zhang, Ying Jiang. The drafts of the manuscript were written by Denise Marie Francisco, MD with the guidance of Pablo C. Okhuysen, MD and all authors commented and added on previous versions of the manuscript. All authors read and approved the final manuscript. Denise Marie Francisco, MD has no competing interests and she has changed her affiliation to the University of Illinois College of Medicine in Peoria. Samuel L. Aitken has also changed his affiliation to the University of Michigan. Ryan Dillon, MsC and Engels N. Obi, PhD are employed under Merck Sharp & Dohme Corp., a subsidiary of Merck & Co., Inc., Kenilworth, NJ, USA. Pablo C. Okhuysen, MD has faculty grant/research support from Merck Sharp and Dohme Corp, Deinove, Summit, Melinta and Napo. He is a paid consultant to Napo and is a consultant with Ferring Pharmaceuticals, Inc. This study was performed in accordance with the Helsinki Declaration of 1964 and its later amendments. The study was reviewed and approved by the University of Texas MD Anderson Cancer Center Institutional Review Board (OHRP IORG0000083). Written, informed consent was obtained from all study subjects prior to enrollment in the study and included consent to publish data in aggregate and devoid of all identifiers. A portion of the data was presented during the Infectious Diseases Society of America – IDWeek 2020 (October 21–25, 2020 held as a virtual conference, online) as an abstract entitled “Metronidazole Exposure Prior to Clostridiodes difficile Infection (CDI) is a Risk Factor for Severe C. difficile Disease in Cancer Patients”. The de-identified datasets generated during and/or analyzed during the current study are available from the corresponding author on reasonable request. Publisher Copyright: {\textcopyright} Merck & Co., Inc., Rahway, NJ, USA and its affiliates, and Denise Marie Francisco, Liangliang Zhang, Ying Jiang, Adilene Olvera, Javier Adachi, Eduardo Yepez Guevara, Samuel Aitken, Kevin Garey, Christine Peterson, Kim-Anh Do, Robert Jenq and Pablo Okhuysen 2022.",
year = "2023",
month = jan,
doi = "10.1007/s40121-022-00722-9",
language = "English (US)",
volume = "12",
pages = "209--225",
journal = "Infectious Diseases and Therapy",
issn = "2193-8229",
publisher = "Springer Healthcare",
number = "1",
}