Clostridium difficile Infection Is Associated With Increased Risk of Death and Prolonged Hospitalization in Children

Julia Shaklee Sammons () 0 1 2 Russell Localio 1 Rui Xiao 1 Susan E. Coffin 0 1 2 Theoklis Zaoutis 1 2 3 0 Infection Prevention and Control 1 Received 16 October 2012; accepted 6 February 2013; electronically published 26 March 2013. of Philadelphia, Department of Infection Prevention and Control , Main Building, Clinical Infectious Diseases 2013;57(1):1-8 The Author 2013. Published by Oxford University Press on behalf of the Infectious Diseases Society of America. All rights reserved. For Permissions , please 2 Division of Infectious Diseases, and Departments of 3 The Center for Pediatric Clinical Effectiveness Research, The Children's Hospital of Philadelphia , Pennsylvania Background. Clostridium difficile infection (CDI) is associated with significant morbidity and mortality among adults. However, outcomes are poorly defined among children. Methods. A retrospective cohort study was performed among hospitalized children at 41 children's hospitals between January 2006 and August 2011. Patients with CDI (exposed) were matched 1:2 to patients without CDI (unexposed) based on the probability of developing CDI ( propensity score derived from patient characteristics). Exposed subjects were stratified by C. difficile test date, suggestive of community-onset (CO) versus hospital-onset (HO) CDI. Outcomes were analyzed for matched subjects. Results. We identified 5107 exposed and 693 409 unexposed subjects. Median age was 6 years (interquartile range [IQR], 2-13 years) for exposed and 8 years (IQR, 3-14 years) for unexposed subjects. Of these, 4474 exposed were successfully matched to 8821 unexposed by propensity score. In-hospital mortality differed significantly (CDI, 1.43% vs matched unexposed, 0.66%; P < .001). Mortality rates were similar between CO-CDI and matched subjects. However, mortality rates were significantly greater among HO-CDI compared with matched unexposed (odds ratio, 6.73 [95% confidence interval {CI}, 3.77-12.02]). Mean differences in length of stay (LOS) and total cost were significant: 5.55 days (95% CI, 4.54-6.56 days) and $18 900 (95% CI, $15 100-$22 700) for CO-CDI, and 21.60 days (95% CI, 19.29-23.90 days) and $93 600 (95% CI, $80 000-$107 200) for HO-CDI. Conclusions. Pediatric CDI is associated with increased mortality, longer LOS, and higher costs. These findings underscore the importance of antibiotic stewardship and infection control programs to prevent this disease in children. - Clostridium difficile is the most common cause of hospital-acquired diarrhea among adults and is associated with significant morbidity, mortality, and healthcare costs [1, 2]. Over the past decade, the epidemiology of C. difficile infection (CDI) has changed dramatically in conjunction with the emergence of a hypervirulent strain of C. difficile, referred to as the North American pulsed-field gel electrophoresis type 1 strain (NAP1), including a rise in CDI among persons in the community [3]. In addition, several studies have reported an increase in CDI among children in both inpatient and ambulatory care settings [48]. Still, outcomes associated with CDI among children are poorly characterized. Among adults, CDI is associated with increased mortality and healthcare utilization among hospitalized patients, particularly in intensive care settings and among those with comorbidities [914]. However, dedicated studies evaluating the impact of CDI on outcomes of hospitalized children are limited. Historically, C. difficile was believed to cause less significant disease among children compared with adults; however, severe cases of CDI have been reported, and the NAP1 strain has been identified in children [1518]. As the epidemiology of CDI has changed, additional studies evaluating associated outcomes are needed to better understand its impact among hospitalized children. MATERIALS AND METHODS Study Design We performed a retrospective, multicenter cohort study to assess outcomes associated with CDI among a cohort of hospitalized children at 41 free-standing childrens hospitals. Primary outcomes were in-hospital mortality, length of stay (LOS), and total standardized cost. This study was reviewed and approved by the Institutional Review Board of the Childrens Hospital of Philadelphia. Data Source The Pediatric Health Information System (PHIS) database is a comprehensive database containing clinical and financial details of >6 million admissions from 43 Child Health Corporation of America hospitals. Member hospitals represent 17 of 20 major metropolitan areas across the United States, with one childrens hospital representing each city. Data elements include demographics, admission and discharge dates, International Classification of Diseases, Ninth Revision, Clinical Modification (ICD-9-CM) diagnosis and procedure codes, payer information, and specific financial utilization data ( pharmacy, imaging, and clinical services). All patients have a primary diagnosis code plus up to 20 secondary diagnoses, coded at discharge. Pharmacy data include the date, type, and administration route of any medication ordered. Study Population Children aged 12 months to 18 years admitted to PHIS hospitals for at least 3 days between 1 January 2006 and 1 August 2011 were eligible for the study. Patients with CDI (exposed) were identified by the presence of an ICD-9-CM code for CDI (code 008.45) plus a C. difficile test charge, based on a validated case finding tool [19]. This ICD-9-CM code is the only code specific for CDI. For subjects with multiple CDI-related admissions, only the first admission was used. Patients without CDI (unexposed) were selected from among hospitalized children without the CDI ICD-9-CM code. Exposed subjects tested for C. difficile before hospital day 3 were defined as having community-onset (CO) CDI, as patients presenting with symptoms upon admission would be expected to be tested by that time [14]. Exposed subjects tested on or after hospital day 3 were defined as having hospital-onset (HO) CDI. Day of admission was defined as hospital day 0. Data Collection All data were obtained from the PHIS database. Clinical and demographic data collected included age, sex, race, comorbid diagnoses, in-hospital procedures, and medication exposure, including antimicrobial agents, proton pump inhibitors or H2 blockers, and total parenteral nutrition. The presence of comorbidities was assessed using a previously validated ICD-9-CM codebased diagnostic classification system for pediatric chronic conditions [20]. Data collected on underlying severity of illness included admission to the intensive care unit (ICU) and receipt of respiratory (supplemental oxygen or mechanical ventilation) or pressor support (dopamine, epinephrine, dobutamine, or norepinephrine). Data Analysis Propensity Score Matching To balance important patient characteristics between groups, we implemented stratified and propensity scorebased matching. We developed propensity scores that represented e (...truncated)