Risk factors for in-hospital mortality among a cohort of children with Clostridium difficile infection.

OBJECTIVE: The incidence of Clostridium difficile infection (CDI) has increased and has been associated with poor outcomes among hospitalized children, including increased risk of death. The purpose of this study was to identify risk factors for all-cause in-hospital mortality among children with CDI. METHODS: A multicenter cohort of children with CDI, aged 1-18 years, was established among children hospitalized at 41 freestanding children's hospitals between January 1, 2006 and August 31, 2011. Children with CDI were identified using a validated case-finding tool (ICD-9-CM code for CDI plus C. difficile test charge). Only the first CDI-related hospitalization during the study period was used. Risk factors for all-cause in-hospital mortality within 30 days of C. difficile test were evaluated using a multivariable logistic regression model. RESULTS: We identified 7,318 children with CDI during the study period. The median age of this cohort was 6 years [interquartile range (IQR): 2-13]; the mortality rate was 1.5% (n=109); and the median number of days between C. difficile testing and death was 12 (IQR, 7-20). Independent risk factors for death included older age [adjusted odds ratio (OR, 95% confidence interval), 2.29 (1.40-3.77)], underlying malignancy [3.57 (2.36-5.40)], cardiovascular disease [2.06 (1.28-3.30)], hematologic/immunologic condition [1.89 (1.05-3.39)], gastric acid suppression [2.70 (1.43-5.08)], and presence of >1 severity of illness marker [3.88 (2.44-6.19)]. CONCLUSION: Patients with select chronic conditions and more severe disease are at increased risk of death. Identifying risk factors for in-hospital mortality can help detect subpopulations of children that may benefit from targeted CDI prevention and treatment strategies.

Variation in Risk of Hospital-Onset Clostridium difficile Infection Across ß-Lactam Antibiotics in Children With New-Onset Acute Lymphoblastic Leukemia.

BACKGROUND: Antibiotic exposure is common among children with leukemia. However, limited data exist regarding the risk of Clostridium difficile infection (CDI) across anti-pseudomonal ß-lactam antibiotics commonly used for fever and neutropenia. METHODS: A multicenter cohort of children with newly diagnosed acute lymphoblastic leukemia (ALL) was established from 43 freestanding children's hospitals from 1999 to 2009. Patients were followed until their index CDI event, defined by the CDI ICD-9 code plus a C difficile test charge, or until 180 days from ALL diagnosis. Cox proportional hazards models were performed to identify the hazards of CDI after exposure to anti-pseudomonal ß-lactams, adjusting for demographics, other antibiotic exposures, severity of illness, antacids, gastrointestinal manipulation, and confounding by hospital. RESULTS: A cohort of 8268 ALL patients was assembled; median age was 5.5 years (interquartile range, 3.26-10.58). Two-hundred sixty-eight (3.2%) patients developed CDI within 180 days of ALL diagnosis. Each 1-day increase in exposure to an anti-pseudomonal ß-lactam within the prior 30 days was associated with a significantly increased risk for CDI (hazard ratio [HR], 1.05; 95% confidence interval [CI], 1.01, 1.09). Ceftazidime (HR, 1.05; 95% CI, 1.02, 1.08) and cefepime (HR, 1.07; 95% CI, 1.02, 1.12) were each independently associated with CDI. CONCLUSIONS: Efforts to reduce total exposure to anti-pseudomonal ß-lactam agents may help to reduce the risk of CDI in children with newly diagnosed ALL. Cefepime and ceftazidime were independently associated with CDI, whereas anti-pseudomonal penicillins and carbapenems were not. These findings, if confirmed, have potential implications for antibiotic choice during periods of fever and neutropenia.

Clostridium difficile Infection in children.

Clostridium difficile is the most common cause of health care-associated diarrhea among adults in the United States and is associated with significant morbidity and mortality. During the past decade, the epidemiology of C difficile infection (CDI) has changed, including a rise in the rate and severity of infection related to the emergence of a hypervirulent strain as well as an increase in disease among outpatients in community settings. Although less is known about CDI among pediatric patients, C difficile is increasingly recognized as an important pathogen among children. In this review, we discuss recent updates in the incidence and epidemiology of CDI among children, including risk factors for infection, and highlight the importance of CDI in special populations of children, particularly those with inflammatory bowel disease or cancer. In addition, we review current knowledge in the areas of diagnosis and management of CDI among children and highlight future areas for research.