Clostridium difficile infection is associated with increased risk of death and prolonged hospitalization in children.

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.

Recent trends in the epidemiology and treatment of C. difficile infection in children.

PURPOSE OF REVIEW: Clostridium difficile is the most common cause of healthcare-associated diarrhea among adults in Western countries, and is increasingly recognized as an important pathogen in children. This review provides an update on the changing epidemiology of C. difficile infection (CDI) for pediatric providers and summarizes current knowledge regarding available therapies. RECENT FINDINGS: The incidence of CDI has more than doubled among adults over the past decade, with a particular rise in incidence among patients presenting from the community. CDI has also increased among children in both inpatient and outpatient settings and there is growing evidence that specific populations of children may be at highest risk. Antibiotic-based therapies remain the mainstay of treatment for CDI, but new therapies have been developed with potential future applications in children. Use of nonantibiotic-based therapies is limited in children, but their use has been studied among adults with intractable or recurrent disease. SUMMARY: The rise in incidence of CDI over the past decade warrants increased recognition by pediatric providers. Knowledge of the pediatric populations at highest risk for infection as well as the options for therapy will improve understanding of this changing disease.

Administration of Palivizumab in the NICU.

BACKGROUND: The American Academy of Pediatrics recommends palivizumab prophylaxis against respiratory syncytial virus (RSV) for infants at high risk for severe disease within 72 hours of hospital discharge to prevent community-associated RSV. The American Academy of Pediatrics does not recommend palivizumab to prevent health care-associated RSV (HA-RSV). METHODS: A retrospective, multicenter cohort of hospitalized infants who received nondischarge palivizumab (NDP) between January 2009 and December 2013 was established from 14 hospitals. NDP was defined as a charge for palivizumab >7 days before hospital discharge and no previous documented RSV. Infants were considered high risk for severe disease if they had chronic lung disease, chronic heart disease, or prematurity. Nondischarge palivizumab use was examined for high- and low-risk infants. HA-RSV was defined as an RSV-positive test (polymerase chain reaction, enzyme immunoassays, or culture) >3 days after admission and the frequency was measured for infants who did and did not receive NDP. RESULTS: We identified 1263 patients who received at least 1 dose of NDP, most of whom were classified as high risk (80%). Among high-risk patients, the predictors of receipt of NDP included longer length of stay, institution, and no comorbid conditions. Most of the low-risk patients (88%) who received NDP had no comorbid conditions. NDP use varied widely among institutions. Overall, 25 eligible patients developed HA-RSV; 17 of whom received NDP. CONCLUSIONS: Despite current recommendations, palivizumab for prevention of HA-RSV was common, even among patients at low risk of severe RSV.

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.

Present or absent on admission: results of changes in National Healthcare Safety Network surveillance definitions.

In January 2013, the National Healthcare Safety Network definition of "present on admission" was created. Using existing surveillance data from 2013, we identified health care-associated infections (HAIs) that met prior present on admission criteria but not the new definition. We identified a number of infections classified as HAI despite evidence that infection was clinically present on admission. These findings have important implications for states with mandatory HAI reporting using National Healthcare Safety Network definitions.

Diagnosis and Management of Clostridium difficile Infection by Pediatric Infectious Diseases Physicians.

BACKGROUND: The incidence of C difficile infection (CDI) has risen among children; however, optimal management of CDI within a diverse pediatric population remains unclear. Although adult guidelines recommend oral vancomycin for treatment of second recurrence or severe CDI, dedicated pediatric data to support pediatric specific management guidelines are lacking. Our objective was to describe current CDI management practices by pediatric infectious diseases (ID) physicians. METHODS: We surveyed pediatric members of the Emerging Infections Network, a network of infectious diseases (ID) physicians across North America, in October 2012. Clinical vignettes were used to determine how physicians modify CDI management based on clinical presentation or presence of comorbidities, including solid organ transplantation, inflammatory bowel disease, and neutropenia. RESULTS: Of the 285 physicians surveyed, 167 (59%) responded. There were no significant differences in geography, level of experience, or hospital type between respondents and non-respondents. All respondents (100%) used oral metronidazole for the initial occurrence of mild CDI in a normal host. Management varied substantially for mild CDI in patients with a variety of comorbidities, in whom metronidazole therapy was less frequently preferred (41-79%). For management of severe CDI, 65% preferred oral vancomycin alone or in combination with at least one other agent. For a second recurrence, oral vancomycin alone or in combination was preferred by 92%. Among 125 respondents who reported using alternative therapies for recurrent or severe CDI, 23 (18%) recommend fecal microbiota transplantation, while 20 (16%) reported using fidaxomicin. CONCLUSIONS: Pediatric ID physicians prefer metronidazole for treatment of mild CDI in healthy children, but management strategies vary for patients with comorbidities or recurrent or severe disease. These findings highlight the need for pediatric comparative effectiveness studies aimed at determining the optimal treatment for pediatric CDI.

Reducing catheter-associated urinary tract infections: a quality-improvement initiative.

BACKGROUND: Catheter-associated urinary tract infections (CAUTIs) are among the most common health care-associated infections in the United States, yet little is known about the prevention and epidemiology of pediatric CAUTIs. METHODS: An observational study was conducted to assess the impact of a CAUTI quality improvement prevention bundle that included institution-wide standardization of and training on urinary catheter insertion and maintenance practices, daily review of catheter necessity, and rapid review of all CAUTIs. Poisson regression was used to determine the impact of the bundle on CAUTI rates. A retrospective cohort study was performed to describe the epidemiology of incident pediatric CAUTIs at a tertiary care children's hospital over a 3-year period (June 2009 to June 2012). RESULTS: Implementation of the CAUTI prevention bundle was associated with a 50% reduction in the mean monthly CAUTI rate (95% confidence interval: -1.28 to -0.12; P = .02) from 5.41 to 2.49 per 1000 catheter-days. The median monthly catheter utilization ratio remained unchanged; ∼90% of patients had an indication for urinary catheterization. Forty-four patients experienced 57 CAUTIs over the study period. Most patients with CAUTIs were female (75%), received care in the pediatric or cardiac ICUs (70%), and had at least 1 complex chronic condition (98%). Nearly 90% of patients who developed a CAUTI had a recognized indication for initial catheter placement. CONCLUSIONS: CAUTI is a common pediatric health care-associated infection. Implementation of a prevention bundle can significantly reduce CAUTI rates in children.

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.