Infection Control & Hospital Epidemiology (2019), 40,420–426 doi:10.1017/ice.2019.23
Original Article
Risk factors for Clostridium difficile infection in pediatric inpatients: A meta-analysis and systematic review Scott Anjewierden BS1,a
, Zheyi Han BS1,a, Charles B. Foster MD2, Chaitanya Pant MD3 and
Abhishek Deshpande MD, PhD4,5 1Cleveland Clinic Lerner College of Medicine, Case Western Reserve University, Cleveland, Ohio, USA, 2Center for Pediatric Infectious Diseases, Cleveland Clinic Children’s, Cleveland, Ohio, USA, 3Division of Gastroenterology, Hepatology and Motility, Department of Internal Medicine, University of Kansas Medical Center, Kansas City, Kansas, USA, 4Medicine Institute Center for Value Based Care Research, Cleveland Clinic, Cleveland, Ohio, USA and 5Department of Infectious Diseases, Cleveland Clinic, Cleveland, Ohio, USA
Abstract
Objective: To summarize risk factors for Clostridioides (formerly Clostridium) difficile infection (CDI) in hospitalized pediatric patients as determined by previous observational studies. Design: Meta-analysis and systematic review. Patients: Studies evaluating risk factors for CDI in pediatric inpatients were eligible for inclusion.
Method:Wesystematically searched MEDLINE,Webof Science, Scopus, andEMBASEfor subject headings and text words related to CDI and pediatrics from 1975 to 2017. Two of the investigators independently screened studies, extracted and compiled data, assessed study quality, and performed the meta-analysis.
Results: Of the 2,033 articles screened, 14 studies reporting 10,531,669 children met the inclusion criteria. Prior antibiotic exposure (odds ratio [OR], 2.14; 95% confidence interval [CI], 1.31–3.52) and proton pump inhibitor (PPI) use (OR, 1.33; 95% CI, 1.07–1.64) were associated with an increased risk of CDI in children. Subgroup analyses using studies reporting only adjusted results suggested that prior antibiotic exposure is not a significant risk factor for CDI. H2 receptor antagonist (H2RA) use (OR, 1.36; 95% CI, 0.31–5.98) and that female gender (OR, 0.87; 95% CI, 0.74–1.03) did not play a significant role as a risk factor for developing CDI.
Conclusion: Prior antibiotic exposure appears to be an important risk factor for CDI based on the combined analysis but not significant using adjusted studies. PPI use was associated with an increased risk of CDI. Judicious and appropriate use of antibiotics and PPIs may help reduce the risk of CDI in this vulnerable population.
(Received 20 November 2018; accepted 19 January 2019)
Clostridioides (formerly Clostridium) difficile is one of the most fre- quent causes of hospital-acquired infections in both adult and pedi- atric patients.1,2 The incidence and healthcare burden of C. difficile infection (CDI) in the hospitalized pediatric population has increased in the past 20 years,3–6mostly attributed to the emergence of the new, hypervirulent strain B1/NAP1/027.7 Althoughmost chil- dren recover without long-term sequelae, CDI in hospitalized chil- dren is associated with increased mortality, length of stay, and hospital cost,5 and it is an independent predictor of subsequent colectomy and discharge to short- or long-term care facility.8 In adult patients, CDI is associated with discrete risk factors including advanced age, antibiotic exposure, prolonged
aAuthors of equal contribution. PREVIOUS PRESENTATION: An abstract containing data used in this study was pre-
sented at the 2018 CSCTR Midwest Clinical and Translational Research Meeting on April 26, 2018, in Chicago, Illinois. Author for correspondence: Abhishek Deshpande, Email:
abhishekdp@gmail.com Cite this article: Anjewierden S, et al. (2019). Risk factors for Clostridium difficile
infection in pediatric inpatients: A meta-analysis and systematic review. Infection Control & Hospital Epidemiology, 40: 420–426,
https://doi.org/10.1017/ice.2019.23
© 2019 by The Society for Healthcare Epidemiology of America. All rights reserved. Methods
All procedures used in this study were consistent with Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) guidelines.14
hospitalization, proton-pump inhibitor use, immunocompromised state, and other medical comorbidities.9 In comparison, risk factors for CDI in children are less well-defined. Notably, antibiotic and proton pump inhibitor (PPI) use have only been variably associated with CDI risk in children.10–12 Additionally, current understanding of pediatric CDI is further complicated by the fact that up to 70% of infants <1 month and up to 2 years of age are colonized with C. difficile but do not develop clinical illness until 12–24 months of age.13 Therefore, closer examination of currently avail- able evidence is needed to better understand the significance and implications of potential risk factors for pediatric CDI. The aim of this meta-analysis and systematic review was to evaluate the association of previously identified risk factors with CDI in hospitalized children.
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