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Intensity of Therapy for Malignancy and Risk for Recurrent and Complicated Clostridium difficile Infection in Children

Willis, Zachary I. MD*; Nicholson, Maribeth R. MD, MPH; Esbenshade, Adam J. MD, MSCI; Xu, Meng MS§; Slaughter, James C. DrPH§; Friedman, Debra L. MD, MS; Edwards, Kathryn M. MD; Di Pentima, Maria C. MD, MPH

Journal of Pediatric Hematology/Oncology: August 2019 - Volume 41 - Issue 6 - p 442–447
doi: 10.1097/MPH.0000000000001411
Original Articles

Clostridium difficile infection (CDI) is common in pediatric oncology patients and is often associated with recurrences and complications. We hypothesized that higher intensity of chemotherapy would be associated with these outcomes. We conducted a retrospective cohort study including all cases of primary CDI in children with malignancy in our institution for over 7 years. Intensity of chemotherapy was measured by the Intensity of Treatment Rating Scale, third edition, ranging from level 1 (minimal) to 4 (highest). Outcomes included recurrence within both 56 and 180 days, CDI-associated complications, and primary treatment failure (PTF). Risk of recurrence was compared using Cox proportional hazards regression. Among 192 patients with CDI and malignancy, 122 met inclusion criteria. CDI recurred in 27% (31/115) of patients followed for 56 days and 46% (48/104) of patients followed for 180 days. Fourteen patients (11.4%) had a CDI-associated complication, including 4 intensive care unit admissions and 3 surgical procedures, but no deaths. Ten patients (8.2%) had PTF. Although PTF and severe complications were infrequent, recurrence was common in our cohort. None of these outcomes were associated with level of treatment intensity. More research is required to assess oncologic and nononcologic risk factors for CDI recurrence, PTF, and severe CDI-associated complications.

*Department of Pediatrics, Division of Pediatric Infectious Diseases, University of North Carolina School of Medicine, Chapel Hill, NC

Departments of Pediatrics, D. Brent Polk Division of Gastroenterology, Hepatology, and Nutrition

Pediatrics, Division of Hematology and Oncology


Pediatrics, Division of Pediatric Infectious Diseases, Vanderbilt University School of Medicine, Nashville, TN

Department of Pediatrics, Division of Pediatric Infectious Diseases, Goryeb Children’s Hospital, Morristown, NJ

Z.I.W. and M.R.N. contributed equally.

Z.I.W. was supported by an NIH training grant, T32 AI095202 (PI: Mark Denison, MD); M.R.N. was supported by a CTSA KL2 award, No.UL1 TR000445 (PI Hartmann) and additional support was from an NIH/NCATS grant support UL1 TR000445 for REDCap (Vanderbilt University).

The authors declare no conflict of interest.

Reprints: Maribeth R. Nicholson, MD, MPH, Division of Pediatric Gastroenterology, Hepatology, and Nutrition, Monroe Carell Jr. Children’s Hospital at Vanderbilt 2200 Children’s Way, Nashville, TN 37232 (e-mail:

Received September 26, 2018

Accepted December 13, 2018

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