Editorial commentary: Clostridium difficile in pediatric oncology patients: more questions than answers.

During the past decade, there has been a heightened interest in Clostridium difficile infection (CDI) and its changing epidemiology. According to PubMed, 366 articles were published from 1994 to 2004 about CDI epidemiology, and 1667 articles over the last 9 years.A confluence of factors contributed to the increased number of articles about CDI epidemiology: the emergence of a hypervirulent Clostridium difficile strain (called NAP1) that caused significantmorbidity and mortality among adults, a focus on patient safety and the elimination of healthcare-associated infections (HAIs), and the desire to reduce healthcare costs associated with HAI. CDI is the leading cause of HAI diarrhea, and rivals methicillin-resistant Staphylococcus aureus as the most common cause of HAI. During the last decade, the epidemiology of CDI in the pediatric population has only begun to become elucidated, and has been recently reviewed [1]. Thus, this commentary will focus on pediatric CDI and cancer. Describing CDI epidemiology in persons with cancer is inherently more difficult than in the general population. A problematic issue about CDI among patients with cancer is that its presentation may be confounded by the presence of neutropenic enterocolitis or antibiotic-associated diarrhea not caused by C. difficile. Despite this diagnostic dilemma, a multicenter study of adult cancer centers reports that the pooled incidence rate of hospital-onset CDI was more than twice the National Healthcare Safety Network rate of 7.8 cases per 10 000 patient-days [2]. The incidence of CDI in children was reported to be >15 times greater among children hospitalized with cancer compared with those without cancer [3]. Hospitalized children with malignancy accounted for 15% of a pediatric CDI cohort from a single center, and 25% when using administrative data from multiple freestanding children’s hospitals [4, 5]. Another retrospective, multicenter cohort study examining children with newly diagnosed acute myeloid leukemia (AML) found that 11% of patients had CDI, with a 14% recurrence rate [6]. As with adults with cancer, children with cancer may be more susceptible to CDI due to similar factors: increased contact with the healthcare system, immunosuppression due to chemotherapeutic agents, and repeated prolonged exposure to broad-spectrum antibiotics. In addition to broad-spectrum antibiotic exposure, there may be a differential risk of CDI among the antipseudomonal β-lactam antibioticsused inpatientsduring febrileneutropenia, with cefepime posing a greater risk than antipseudomonal penicillins [7, 8]. Another important risk factor is length of hospital stay associated with development of CDI [3, 7]. Again, each of these studies relies on large administrative databases. A multicenter study of children with AML demonstrated that mandatory hospitalization during prolonged neutropenia was associated with a higher relative incidence rate of CDI [9]. Hospital-onset CDI leads to longer hospitalizations for children admitted for newly diagnosed cancers, similar to findings in the general pediatric population [7, 10]. All pediatric studies of CDI in children with cancer are similar in 2 aspects: There were no deaths directly attributable to CDI, and no samples were collected for molecular analysis. Several limitations become clear when examining what is known about the epidemiology of CDI in children. With many multicenter studies examining risk factors for pediatric CDI relying on administrative databases, the conclusions are tempered by the limitations associated with such data sources: no microbiologic confirmation of laboratory tests, inferred inpatient antibiotic exposure (based on billing data and not medication administration record), and a lack of clinical information at the patient Received 15 April 2014; accepted 16 April 2014; electronically published 29 April 2014. Correspondence: Jason Kim, MD, MSCE, Division of Infectious Diseases, 1202 Abramson Research Center, The Children’s Hospital of Philadelphia, 34th and Civic Center Blvd, Philadelphia, PA 19104 ([email protected]). Clinical Infectious Diseases 2014;59(3):404–5 © The Author 2014. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions, please e-mail: journals. [email protected]. DOI: 10.1093/cid/ciu308