<p><strong>OBJECTIVES: </strong>A polymorphism in the gene encoding β-1,3-glucan synthase, the target of the echinocandin class of antifungals, results in increased in vitro MICs of the echinocandins. This has resulted in controversy surrounding use of the echinocandins for treatment of Candida parapsilosis candidaemia. We aimed to compare 30 day mortality in adults with C. parapsilosis candidaemia treated with echinocandins versus fluconazole.</p>

<p><strong>METHODS: </strong>This is a retrospective observational cohort study. We used the Premier Perspective Database to identify adult patients with C. parapsilosis candidaemia treated with only fluconazole or only an echinocandin as definitive therapy. The primary outcome was 30 day mortality. Propensity scores were derived to estimate the probability the patient would have received either an echinocandin or fluconazole. Inverse probability of treatment weighting (IPTW) was used in a weighted logistic regression to calculate odds of 30 day mortality.</p>

<p><strong>RESULTS: </strong>There were 307 unique patients with C. parapsilosis candidaemia. One hundred and twenty-six (41%) received fluconazole and 181 (59%) received an echinocandin. Age, gender, race, year of admission, need for ICU resources in the week prior to candidaemia onset, and receipt of vasopressors on the day of candidaemia onset were included in the propensity score model used to calculate inverse probability of treatment weights. Weighted logistic regression demonstrated no difference in 30 day mortality between patients receiving an echinocandin as compared with fluconazole (OR 0.82, 95% CI 0.33-2.07).</p>

<p><strong>CONCLUSIONS: </strong>Our result supports the 2016 IDSA invasive candidiasis guidelines, which no longer clearly favour treatment with fluconazole over an echinocandin for C. parapsilosis candidaemia.</p>

<p><strong>OBJECTIVE: </strong>To test the hypothesis that resuscitation with balanced fluids (lactated Ringer [LR]) is associated with improved outcomes compared with normal saline (NS) in pediatric sepsis.</p>

<p><strong>STUDY DESIGN: </strong>We performed matched analyses using data from 12 529 patients &lt;18 years of age with severe sepsis/septic shock at 382 US hospitals between 2000 and 2013 to compare outcomes with vs without LR as part of initial resuscitation. Patients receiving LR were matched 1:1 to patients receiving only NS (NS group), including separate matches for any (LR-any group) or exclusive (LR-only group) LR use. Outcomes included 30-day hospital mortality, acute kidney injury, new dialysis, and length of stay.</p>

<p><strong>RESULTS: </strong>The LR-any group was older, received larger crystalloid volumes, and was less likely to have malignancies than the NS group. After matching, mortality was not different between LR-any (7.2%) and NS (7.9%) groups (risk ratio 0.99, 95% CI 0.98, 1.01; P = .20). There were no differences in secondary outcomes except longer hospital length of stay in LR-any group (absolute difference 2.4, 95% CI 1.4, 5.0 days; P &lt; .001). Although LR was preferentially used as adjunctive fluid with large-volume resuscitation or first-line fluid in patients with lower illness severity, outcomes were not different after matching stratified by volume and proportionate LR utilization, including for patients in the LR-only group.</p>

<p><strong>CONCLUSIONS: </strong>Balanced fluid resuscitation with LR was not associated with improved outcomes compared with NS in pediatric sepsis. Although the current practice of NS resuscitation is justified, selective LR use necessitates a prospective trial to definitively determine comparative effectiveness among crystalloids.</p>

<p><strong>BACKGROUND: </strong>There are few contemporary studies of volume-outcome relationships in pediatric oncology. Children with acute lymphoblastic leukemia (ALL) are treated at a wide variety of hospitals. We investigated if inpatient hospital volume influences outcomes. The objective of this study was to evaluate the relationship between inpatient pediatric and pediatric oncology volume and mortality and intensive care resources (ICU care). We hypothesized an inverse relationship between volume and these outcomes.</p>

<p><strong>PATIENTS AND METHODS: </strong>This was a retrospective cohort study. Patients 0 to 18 years of age in the Pediatric Health Information System or Perspective Premier Database from 2009 to 2011 with ALL were included. Exposures were considered as the average inpatient pediatric and pediatric oncology volume. The primary outcome was inpatient mortality; secondary outcome was need for ICU care.</p>

<p><strong>RESULTS: </strong>The included population comprised 3350 patients from 75 hospitals. The inpatient mortality rate was 0.86% (95% confidence interval, 0.58%-1.2%). In the unadjusted analysis, mortality increased as pediatric oncology volume increased from low (0%) to high volume (1.3%) (P&nbsp;= .009). The small number of deaths precluded multivariable analysis of this outcome. Pediatric and pediatric oncology volume was not associated with ICU care when we controlled for potential confounders.</p>

<p><strong>CONCLUSION: </strong>Induction mortality was low. We did not observe an inverse relationship between volume and mortality or ICU care. This suggests that in a modern treatment era, treatment at a low-volume center might not be associated with increased mortality or ICU care in the first portion of therapy. This relationship should be evaluated in other oncology populations with higher mortality rates and with longer-term outcomes.</p>

<p><strong>BACKGROUND: </strong>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).</p>

<p><strong>METHODS: </strong>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 &gt;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) &gt;3 days after admission and the frequency was measured for infants who did and did not receive NDP.</p>

<p><strong>RESULTS: </strong>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.</p>

<p><strong>CONCLUSIONS: </strong>Despite current recommendations, palivizumab for prevention of HA-RSV was common, even among patients at low risk of severe RSV.</p>

<p><strong>BACKGROUND: </strong>Candidemia causes significant morbidity and mortality among children. Removal of a central venous catheter (CVC) is often recommended for adults with candidemia to reduce persistent and metastatic infection. Pediatric-specific data on the impact of CVC retention are limited.</p>

<p><strong>METHODS: </strong>A retrospective cohort study of inpatients &lt;19 years with candidemia at the Children's Hospital of Philadelphia between 2000 and 2012 was performed. The final cohort included patients that had a CVC in place at time of blood culture and retained their CVC at least 1 day beyond the blood culture being positive. A structured data collection instrument was used to retrieve patient data. A discrete time failure model, adjusting for age and the complexity of clinical care before onset of candidemia, was used to assess the association of CVC retention and 30-day all-cause mortality.</p>

<p><strong>RESULTS: </strong>Two hundred eighty-five patients with candidemia and a CVC in place at the time of blood culture were identified. Among these 285 patients, 30 (10%) died within 30 days. Central venous catheter retention was associated with a significant increased risk of death on a given day (odds ratio, 2.50; 95% confidence interval, 1.06-5.91).</p>

<p><strong>CONCLUSIONS: </strong>Retention of a CVC was associated with an increased risk of death after adjusting for age and complexity of care at candidemia onset. Although there is likely persistence of unmeasured confounding, given the strong association between catheter retention and death, our data suggest that early CVC removal should be strongly considered.</p>

<p>Adult data suggest that echinocandins for treatment of candidaemia are associated with decreased mortality, attributed to their fungicidal activity. There are limited data comparing antifungals in children. We compared 30-day all-cause mortality among paediatric candidaemia patients treated with fungicidal vs. fungistatic agents. All inpatients (&gt;6 months and &lt;19 years of age) with candidaemia between 2000 and 2012 at The Children's Hospital of Philadelphia were retrospectively identified. Definitive therapy with fungicidal (amphotericin B and caspofungin) agents was compared with fungistatic (fluconazole) agents. A propensity score model generated the inverse probability of receiving a fungicidal agent, which was included in a weighted logistic regression model. Among 203 children meeting inclusion criteria, 151 (74.4%) and 52 (25.6%) received a fungicidal and fungistatic agent, respectively. Overall, 18 (8.9%) patients died within 30 days. There was no statistically significant difference in mortality between patients started on a fungicidal or fungistatic agent (OR: 2.19, 95% CI: 0.42-11.48). In a propensity score-weighted model, definitive therapy with a fungicidal agent did not result in a significant decrease in mortality. These data suggest that both agents can be considered definitive therapy for paediatric candidaemia. The results should be interpreted with caution given the small sample size. Larger cohort studies are needed.</p>

<p><strong>BACKGROUND: </strong>Bloodstream infection is a major cause of morbidity and mortality. Much of our understanding of the epidemiology and resistance patterns of bloodstream infections comes from studies of hospitalized adults.</p>

<p><strong>METHODS: </strong>We evaluated the epidemiology and antimicrobial resistance of bloodstream infections occurring during an 11-year period in a large, tertiary care children's hospital in the US. All positive blood cultures were identified retrospectively from clinical microbiology laboratory records. We excluded repeat positive cultures with the same organism from the same patient within 30 days and polymicrobial infections.</p>

<p><strong>RESULTS: </strong>We identified 8196 unique episodes of monomicrobial bacteremia in 5508 patients. Overall, 46% were community onset, 72% were Gram-positive bacteria, 22% Gram-negative bacteria and 5% Candida spp. Coagulase negative Staphylococcus was the most common isolated organism. ESKAPE pathogens (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa and Enterobacter spp.) accounted for 20% of episodes. No S. aureus isolate was resistant to vancomycin or linezolid, and no increase in vancomycin minimum inhibitory concentration among methicillin-resistant S. aureus was observed during the study period. Clinically significant increases in vancomycin-resistant Enterococcus, ceftazidime-resistant P. aeruginosa or carbapenem-resistant Enterobacteriaceae were not observed during the study period; however, rates of methicillin-resistant S. aureus increased over time (P &lt; 0.01).</p>

<p><strong>CONCLUSIONS: </strong>Gram-positive and ESKAPE organisms are leading causes of bacteremia in hospitalized children. Although antimicrobial resistance patterns were favorable compared with prior reports of hospitalized adults, multicenter studies with continuous surveillance are needed to identify trends in the emergence of antimicrobial resistance in this setting.</p>

<p>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 &gt;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. Infect Control Hosp Epidemiol 2015;36(10):1183-1189.</p>