Sarah Smathers

Epidemiological Features of Clostridium difficile-Associated Disease Among Inpatients at Children's Hospitals in the United States, 2001–2006

OBJECTIVE. Clostridium difficile is the main cause of nosocomial and antibiotic-associated diarrhea in adults. Recently, the incidence and severity of C difficile-associated disease in adults have been increasing. Whether similar phenomena are occurring among children remains unknown. Our study describes the epidemiological features of C difficile-associated disease in hospitalized children. METHODS. We conducted a retrospective cohort study of hospitalized children with C difficile-associated disease at 22 freestanding childrens hospitals in the United States, from 2001 to 2006. Cases of C difficile-associated disease were defined as a hospitalized child with a discharge code for C difficile infection, a laboratory billing charge for a C difficile toxin assay, and receipt of antimicrobial therapy for C difficile-associated disease. RESULTS. We identified 4895 patients with C difficile-associated disease. Over the study period, the annual incidence of C difficile-associated disease increased from 2.6 to 4.0 cases per 1000 admissions and from 4.4 to 6.5 cases per 10 000 patient-days. The median age of children with C difficile-associated disease was 4 years. Twenty-six percent of patients were <1 year of age. The majority of patients (67%) had underlying chronic medical conditions. The colectomy and all-cause mortality rates among children with C difficile-associated disease did not increase during the study period. CONCLUSIONS. The annual incidence of C difficile-associated disease in hospitalized children increased significantly from 2001 to 2006. However, the rates of colectomy and in-hospital death have not increased in children with C difficile-associated disease as they have among adults. The risk factors and outcomes for children with C difficile-associated disease remain to be defined in future studies.

Trends in the incidence of methicillin-resistant Staphylococcus aureus infection in children's hospitals in the United States.

BACKGROUND The incidence of and outcomes associated with methicillin-resistant Staphylococcus aureus (MRSA) infection in hospitalized children have been incompletely characterized. METHODS We performed a retrospective, observational study using the Pediatric Health Information System, a database of clinical and financial data from >40 freestanding US childrens hospitals. Using discharge coding data, we characterized S. aureus infections in children <18 years of age who were hospitalized during the period from 1 January 2002 through 31 December 2007. RESULTS During this 6-year study period, we identified 57,794 children with S. aureus infection, 29,309 (51%) of whom had MRSA infection. The median age of patients with S. aureus infection was 3.1 years (interquartile range, 0.8-11.2 years), and less than one-third of these patients had complex, chronic medical conditions. Over time, there was a significant increase in cases of MRSA infection (from 6.7 cases per 1000 admissions in 2002 to 21.1 cases per 1000 admissions in 2007; P = .02, by test for trend), whereas the incidence of methicillin-susceptible S. aureus infection remained stable (14.1 cases per 1000 patient-days in 2002 to 14.7 cases per 1000 patient-days in 2007; P = .85, by test for trend). Of the 38,123 patients whose type of infection was identified, 23,280 (61%) had skin and soft-tissue infections. The incidences of skin and soft-tissue infection, pneumonia, osteomyelitis, and bacteremia that were caused by S. aureus increased over time, and these increases were due exclusively to MRSA. The mortality rate for hospitalized children with MRSA infection was 1% (360 of 29,309 children). CONCLUSIONS There has been a recent increase in the number of hospitalized children with MRSA infection. This increase is largely driven by, but is not limited to, an increase in skin and soft-tissue infections. The mortality rate for hospitalized children with MRSA infection is low.

Risk factors and outcomes associated with severe Clostridium difficile infection in children

Background: The incidence and severity of Clostridium difficile infection (CDI) is increasing among adults; however, little is known about the epidemiology of CDI among children. Methods: We conducted a nested case-control study to identify the risk factors for and a prospective cohort study to determine the outcomes associated with severe CDI at 2 childrens hospitals. Severe CDI was defined as CDI and at least 1 complication or ≥2 laboratory or clinical indicators consistent with severe disease. Studied outcomes included relapse, treatment failure, and CDI-related complications. Isolates were tested to determine North American pulsed-field gel electrophoresis type 1 lineage. Results: We analyzed 82 patients with CDI, of whom 48 had severe disease. Median age in years was 5.93 (1.78–12.16) and 1.83 (0.67–8.1) in subjects with severe and nonsevere CDI, respectively (P = 0.012). All patients with malignancy and CDI had severe disease. Nine subjects (11%) had North American pulsed-field gel electrophoresis type 1 isolates. Risk factors for severe disease included age (adjusted odds ratio [95% confidence interval]: 1.12 [1.02, 1.24]) and receipt of 3 antibiotic classes in the 30 days before infection (3.95 [1.19, 13.11]). If infants less than 1 year of age were excluded, only receipt of 3 antibiotic classes remained significantly associated with severe disease. Neither the rate of relapse nor treatment failure differed significantly between patients with severe and nonsevere CDI. There was 1 death. Conclusions: Increasing age and exposure to multiple antibiotic classes were risk factors for severe CDI. Although most patients studied had severe disease, complications were infrequent. Relapse rates were similar to those reported in adults.

Recurrence rate of clostridium difficile infection in hospitalized pediatric patients with inflammatory bowel disease

Background: The incidence and associated morbidity of Clostridium difficile (CD) infection has been increasing at an alarming rate in North America. Clostridium difficile‐associated diarrhea (CDAD) is the leading cause of nosocomial diarrhea in the USA. Patients with CDAD have longer average hospital admissions and additional hospital costs. Evidence has demonstrated that patients with inflammatory bowel disease (IBD) have a higher incidence of CD in comparison to the general population. The aim of this study was to compare the rate of recurrence of CD in hospitalized pediatric patients with IBD compared to hospitalized controls. The secondary aim was to evaluate whether infection with CD resulted in a more severe disease course of IBD. Methods: This was a nested case control retrospective study of hospitalized pediatric patients. Diagnosis of CD was confirmed with stool Toxin A and B analysis. The following data were obtained from the medical records: demographic information, classification of IBD including location of disease, IBD therapy, and prior surgeries. In addition, prior hospital admissions within 1 year and antibiotic exposure were recorded. The same information was recorded following CD infection. Cases were patients with IBD and CD; two control populations were also studied: patients with CD but without IBD, and patients with IBD but without CD. Results: For aim 1, a total of 111 eligible patients with IBD and CD infection and 77 eligible control patients with CD infection were included. The rate of recurrence of CD in the IBD population was 34% compared to 7.5% in the control population (P < 0.0001). In evaluating the effect of CD infection on IBD disease severity, we compared the 111 IBD patients with CD to a second control population of 127 IBD patients without CD. 57% of IBD‐CD patients were readmitted with an exacerbation of disease within 6 months of infection with CD and 67% required escalation of therapy following CD infection, compared to 30% of IBD patients without CD (P < 0.001). Of the patients with IBD and CD, 44% of the cases were new‐onset IBD, 63% were on immunosuppression therapy, and 33% were on gastric acid suppression prior to infection. In comparing the IBD‐CD and control CD populations, there was no significant difference in antibiotic exposure: 33% of IBD patients and 26% of control patients were on antibiotics (P < 0.2). With regard to prior hospitalization, 10% of patients with IBD were hospitalized in the 30 days prior to infection in comparison to 27% of the control CD patients (P < 0.002). Conclusions: CD infection in patients with IBD results in a higher rate of recurrence and is associated with higher morbidity than the general population. Patients with IBD often required hospitalization and escalation of therapy following infection with CD, suggesting that CD resulted in increased severity of IBD disease. In addition, IBD patients were more likely develop community‐acquired CD, while the control patients developed nosocomial infections, indicating a higher susceptibility to CD infection in patients with IBD. (Inflamm Bowel Dis 2011;)

Presence of the epidemic North American Pulsed Field type 1 Clostridium difficile strain in hospitalized children.

A hypervirulent strain of Clostridium difficile-labeled North American Pulsed Field type 1 causes severe disease in adults. To determine the prevalence of NAP1 C. difficile in children, organisms from consecutive C. difficile toxin-positive stool samples at 2 childrens hospitals microbiology laboratories were characterized. We found that 19.4% of these samples were NAP1.

High Proportion of False-Positive Clostridium difficile Enzyme Immunoassays for Toxin A and B in Pediatric Patients

OBJECTIVES To determine the frequency of false-positive Clostridium difficile toxin enzyme immunoassay (EIA) results in hospitalized children and to examine potential reasons for this false positivity. DESIGN Nested case-control. SETTING Two tertiary care pediatric hospitals. METHODS As part of a natural history study, prospectively collected EIA-positive stools were cultured for toxigenic C. difficile, and characteristics of children with false-positive and true-positive EIA results were compared. EIA-positive/culture-negative samples were recultured after dilution and enrichment steps, were evaluated for presence of the tcdB gene by polymerase chain reaction (PCR), and were further cultured for Clostridium sordellii, a cause of false-positive EIA toxin assays. RESULTS Of 112 EIA-positive stools cultured, 72 grew toxigenic C. difficile and 40 did not, indicating a positive predictive value of 64% in this population. The estimated prevalence of C. difficile infection (CDI) in the study sites among children tested for this pathogen was 5%-7%. Children with false-positive EIA results were significantly younger than those with true-positive tests but did not differ in other characteristics. No false-positive specimens yielded C. difficile when cultured after enrichment or serial dilution, 1 specimen was positive for tcdB by PCR, and none grew C. sordellii. CONCLUSIONS Approximately one-third of EIA tests used to evaluate pediatric inpatients for CDI were falsely positive. This finding was likely due to the low prevalence of CDI in pediatric hospitals, which diminishes the tests positive predictive value. These data raise concerns about the use of EIA assays to diagnosis CDI in children.

Opportunities for antibiotic reduction in mechanically ventilated children.

Objective: To identify opportunities to safely reduce antibiotic use in critically ill children with moderately severe respiratory failure. Design: Prospective observational. Setting: Four pediatric intensive care units at three American tertiary care childrens hospitals. Patients: Children aged 2 months to 18 yrs who were mechanically ventilated, had an abnormal chest radiograph, and for whom the attending physicians had initiated antibiotics for presumed bacterial pneumonia. Intervention: Nonbronchoscopic bronchoalveolar lavage. Methods and Main Results: Eligible children were subjected to nonbronchoscopic bronchoalveolar lavage within 12 hrs of initiating antibiotics. The concentration of bacteria in the lavage fluid was determined by quantitative assay, and the diagnosis of pneumonia was confirmed if >104 pathogenic bacteria/mL were cultivated. Twenty-one subjects were enrolled, in whom 20 nonbronchoscopic bronchoalveolar lavage procedures were completed. Six of 20 subjects had nonbronchoscopic bronchoalveolar lavage results confirmatory of bacterial pneumonia, three additional subjects had bacteria isolated at concentrations below levels conventionally used to diagnose bacterial pneumonia, and the remaining 11 demonstrated no growth. Clinical parameters reflective of severity of disease and laboratory parameters reflective of systemic and local inflammation were tested for their association with a positive nonbronchoscopic bronchoalveolar lavage, but none was demonstrated. Conclusions: Eleven of 20 mechanically ventilated children treated with antibiotics for presumed infectious pneumonia had undetectable concentrations of bacteria in their lower respiratory tract, and three others had organisms present at low concentrations, suggesting that opportunities exist to reduce antibiotic exposure in this population.

Outbreak of Adenovirus in a Neonatal Intensive Care Unit: Critical Importance of Equipment Cleaning During Inpatient Ophthalmologic Examinations

PURPOSE Outbreaks of adenovirus in neonatal intensive care units (NICUs) can lead to widespread transmission and serious adverse outcomes. We describe the investigation, response, and successful containment of an adenovirus outbreak in a NICU associated with contaminated handheld ophthalmologic equipment used during retinopathy of prematurity (ROP) screening. DESIGN Epidemiologic outbreak investigation. PARTICIPANTS A total of 23 hospitalized neonates, as well as NICU staff and parents of affected infants. MAIN OUTCOME MEASURES Routine surveillance identified an adenovirus outbreak in a level IV NICU in August 2016. Epidemiologic investigation followed, including chart review, staff interviews, and observations. Cases were defined as hospital-acquired adenovirus identified from any clinical specimen (NICU patient or employee) or compatible illness in a family member. Real-time polymerase chain reaction (PCR) and partial- and whole-genome sequencing assays were used for testing of clinical and environmental specimens. RESULTS We identified 23 primary neonatal cases and 9 secondary cases (6 employees and 3 parents). All neonatal case-patients had respiratory symptoms. Of these, 5 developed pneumonia and 12 required increased respiratory support. Less than half (48%) had ocular symptoms. All neonatal case-patients (100%) had undergone a recent ophthalmologic examination, and 54% of neonates undergoing examinations developed adenovirus infection. All affected employees and parents had direct contact with infected neonates. Observations revealed inconsistent disinfection of bedside ophthalmologic equipment and limited glove use. Sampling of 2 handheld lenses and 2 indirect ophthalmoscopes revealed adenovirus serotype 3 DNA on each device. Sequence analysis of 16 neonatal cases, 2 employees, and 2 lenses showed that cases and equipment shared 100% identity across the entire adenovirus genome. Infection control interventions included strict hand hygiene, including glove use; isolation precautions; enhanced cleaning of lenses and ophthalmoscopes between all examinations; and staff furlough. We identified no cases of secondary transmission among neonates. CONCLUSIONS Adenovirus outbreaks can result from use of contaminated ophthalmologic equipment. Even equipment that does not directly contact patients can facilitate indirect transmission. Patient-to-patient transmission can be prevented with strict infection control measures and equipment cleaning. Ophthalmologists performing inpatient examinations should take measures to avoid adenoviral spread from contaminated handheld equipment.

Development of a novel prevention bundle for pediatric healthcare-associated viral infections

OBJECTIVE To reduce the healthcare-associated viral infection (HAVI) rate to 0.70 infections or fewer per 1,000 patient days by developing and sustaining a comprehensive prevention bundle. SETTING A 546-bed quaternary-care childrens hospital situated in a large urban area.PatientsInpatients with a confirmed HAVI were included. These HAVIs were identified through routine surveillance by infection preventionists and were confirmed using National Healthcare Safety Network definitions for upper respiratory infections (URIs), pneumonia, and gastroenteritis. METHODS Quality improvement (QI) methods and statistical process control (SPC) analyses were used in a retrospective observational analysis of HAVI data from July 2012 through June 2016. RESULTS In total, 436 HAVIs were identified during the QI initiative: 63% were URIs, 34% were gastrointestinal infections, and 2.5% were viral pneumonias. The most frequent pathogens were rhinovirus (n=171) and norovirus (n=83). Our SPC analysis of HAVI rate revealed a statistically significant reduction in March 2014 from a monthly average of 0.81 to 0.60 infections per 1,000 patient days. Among HAVIs with event reviews completed, 15% observed contact with a sick primary caregiver and 15% reported contact with a sick visitor. Patient outcomes identified included care escalation (37%), transfer to ICU (11%), and delayed discharge (19%). CONCLUSIONS The iterative development, implementation, and refinement of targeted prevention practices was associated with a significant reduction in pediatric HAVI. These practices were ultimately formalized into a comprehensive prevention bundle and provide an important framework for both patient and systems-level interventions that can be applied year-round and across inpatient areas.

933Between a Rock and a Hard Place: Why Physicians and Advanced Practice Providers Work While Sick

Practice Providers Work While Sick Julia E. Szymczak, PhD; Sarah Smathers, MPH, CIC; Cindy Hoegg, BSN, RN, CIC; Sarah B. Klieger, MPH; Julia Shaklee Sammons, MD, MSCE; Division of Infectious Diseases, Center for Pediatric Clinical Effectiveness, The Children’s Hospital of Philadelphia, Philadelphia, PA; Division of Infection Prevention and Control, The Children’s Hospital of Philadelphia, Philadelphia, PA; Perelman School of Medicine, Department of Pediatrics, Division of Infectious Diseases, Department of Infection Prevention and Control, The Children’s Hospital of Philadelphia, Philadelphia, PA