Prospective Evaluation of the Fungitell® (1→3) Beta-D-Glucan Assay as a Diagnostic Tool for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplantation: A Report from the Children's Oncology Group.

BACKGROUND: Invasive fungal disease (IFD) is a major source of morbidity and mortality for hematopoietic cell transplant (HCT) recipients. Non-invasive biomarkers, such as the beta-D-glucan assay, may improve the diagnosis of IFD. The objective was to define the utility of surveillance testing using Fungitell® beta-D-glucan (BDG) assay in children receiving antifungal prophylaxis in the immediate post-HCT period. METHODS: Weekly surveillance blood testing with the Fungitell® BDG assay was performed during the early post-HCT period in the context of a randomized trial of children, adolescents, and young adults undergoing allogeneic HCT allocated to triazole or caspofungin prophylaxis. Positivity was defined at the manufacturer cutoff of 80 pg/ml. IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for the Fungitell® BDG assay for the outcome of proven or probable IFD. RESULTS: A total of 51 patients (out of 290 patients in the parent trial) contributed blood specimens. In total, 278 specimens were evaluated. Specificity was 80.8% (95% confidence interval [CI]: 75.6%-85.3%), and NPV was over 99% (95% CI: 86.8%-99.9%). However, there were no true positive results, resulting in sensitivity of 0% (95% CI: 0.0%-84.2%) and PPV of 0% (95% CI: 0.0%-6.7%). CONCLUSIONS: Fungitell® BDG screening is of limited utility in diagnosing IFD in the post-HCT period, mainly due to high false-positive rates. Fungitell® BDG surveillance testing should not be performed in children during the early post-HCT period while receiving antifungal prophylaxis as the pretest probability for IFD is low.

Prospective Evaluation of Galactomannan and (1→3) ß-d-Glucan Assays as Diagnostic Tools for Invasive Fungal Disease in Children, Adolescents, and Young Adults With Acute Myeloid Leukemia Receiving Fungal Prophylaxis.

BACKGROUND: Patients receiving chemotherapy for acute myeloid leukemia (AML) are at high risk for invasive fungal disease (IFD). Diagnosis of IFD is challenging, leading to interest in fungal biomarkers. The objective was to define the utility of surveillance testing with Platelia Aspergillus galactomannan (GM) enzyme immunoassay (EIA) and Fungitell ß-d-glucan (BDG) assay in children with AML receiving antifungal prophylaxis. METHODS: Twice-weekly surveillance blood testing with GM EIA and BDG assay was performed during periods of neutropenia in the context of a randomized trial of children, adolescents, and young adults with AML allocated to fluconazole or caspofungin prophylaxis. Proven or probable IFD was adjudicated using blinded central reviewers. The sensitivity, specificity, positive predictive value (PPV), and negative predictive value (NPV) were calculated for Platelia and Fungitell assays alone and in combination for the outcomes of proven and probable invasive aspergillosis (IA) or invasive candidiasis (IC). RESULTS: Among 471 patients enrolled, 425 participants (209 fluconazole and 216 caspofungin) contributed ≥1 blood specimen. In total, 6103 specimens were evaluated, with a median of 15 specimens per patient (range 1-43). The NPV was >99% for GM EIA and BDG assay alone and in combination. However, there were no true positive results, resulting in sensitivity and PPV for each assay of 0%. CONCLUSIONS: The GM EIA and the BDG assay alone or in combination were not successful at detecting IA or IC during periods of neutropenia in children, adolescents, and young adults with AML receiving antifungal prophylaxis. Utilization of these assays for surveillance in this clinical setting should be discouraged.

A Randomized Trial of Caspofungin vs Triazoles Prophylaxis for Invasive Fungal Disease in Pediatric Allogeneic Hematopoietic Cell Transplant.

BACKGROUND: Children and adolescents undergoing allogeneic hematopoietic cell transplantation (HCT) are at high risk for invasive fungal disease (IFD). METHODS: This multicenter, randomized, open-label trial planned to enroll 560 children and adolescents (3 months to <21 years) undergoing allogeneic HCT between April 2013 and September 2016. Eligible patients were randomly assigned to antifungal prophylaxis with caspofungin or a center-specific comparator triazole (fluconazole or voriconazole). Prophylaxis was administered from day 0 of HCT to day 42 or discharge. The primary outcome was proven or probable IFD at day 42 as adjudicated by blinded central review. Exploratory analysis stratified this evaluation by comparator triazole. RESULTS: A planned futility analysis demonstrated a low rate of IFD in the comparator triazole arm, so the trial was closed early. A total of 290 eligible patients, with a median age of 9.5 years (range 0.3-20.7), were randomized to caspofungin (n = 144) or a triazole (n = 146; fluconazole, n = 100; voriconazole, n = 46). The day 42 cumulative incidence of proven or probable IFD was 1.4% (95% confidence interval [CI], 0.3%-5.4%) in the caspofungin group vs 1.4% (95% CI, 0.4%-5.5%) in the triazole group (P = .99, log-rank test). When stratified by specific triazole, there was no significant difference in proven or probable IFD at day 42 between caspofungin vs fluconazole (1.0%, 95% CI, 0.1%-6.9%, P = .78) or caspofungin vs voriconazole (2.3%, 95% CI, 0.3%-15.1%, P = .69). CONCLUSIONS: In pediatric HCT patients, prophylaxis with caspofungin did not significantly reduce the cumulative incidence of early proven or probable IFD compared with triazoles. Future efforts to decrease IFD-related morbidity and mortality should focus on later periods of risk. TRIAL REGISTRATION: NCT01503515.

Surveillance for central-line-associated bloodstream infections: Accuracy of different sampling strategies.

BACKGROUND: Active daily surveillance of central-line days (CLDs) in the assessment of rates of central-line-associated bloodstream infections (CLABSIs) is time-consuming and burdensome for healthcare workers. Sampling of denominator data is a method that could reduce the time necessary to conduct active surveillance. OBJECTIVE: To evaluate the accuracy of various sampling strategies in the estimation of CLABSI rates in adult and pediatric units in Greece. METHODS: Daily denominator data were collected across Greece for 6 consecutive months in 33 units: 11 adult units, 4 pediatric intensive care units (PICUs), 12 neonatal intensive care units (NICUs), and 6 pediatric oncology units. Overall, 32 samples were evaluated using the following strategies: (1) 1 fixed day per week, (2) 2 fixed days per week, and (3) 1 fixed week per month. The CLDs for each month were estimated as follows: (number of sample CLDs/number of sampled days) × 30. The estimated CLDs were used to calculate CLABSI rates. The accuracy of the estimated CLABSI rates was assessed by calculating the percentage error (PE): [(observed CLABSI rates - estimated CLABSI rates)/observed CLABSI rates]. RESULTS: Compared to other strategies, sampling over 2 fixed days per week provided the most accurate estimates of CLABSI rates for all types of units. Percentage of estimated CLABSI rates with PE ≤±5% using the strategy of 2 fixed days per week ranged between 74.6% and 88.7% in NICUs. This range was 79.4%-94.1% in pediatric onology units, 62.5%-91.7% in PICUs, and 80.3%-92.4% in adult units. Further evaluation with intraclass correlation coefficients and Bland-Altman plots indicated that the estimated CLABSI rates were reliable. CONCLUSION: Sampling over 2 fixed days per week provides a valid alternative to daily collection of CLABSI denominator data. Adoption of such a monitoring method could be an important step toward better and less burdensome infection control and prevention.

Risk Factors for Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review.

BACKGROUND: Although a number of risk factors have been associated with invasive fungal disease (IFD), a systematic review of the literature to document pediatric-specific factors has not been performed. METHODS: We used the Ovid SP platform to search Medline, Medline In-Process, and Embase for studies that identified risk factors for IFD in children with cancer or those who undergo hematopoietic stem cell transplantation (HSCT). We included studies if they consisted of children or adolescents (<25 years) who were receiving treatment for cancer or undergoing HSCT and if the study evaluated risk factors among patients with and those without IFD. RESULTS: Among the 3566 studies screened, 22 studies were included. A number of pediatric factors commonly associated with an increased risk for IFD were confirmed, including prolonged neutropenia, high-dose steroid exposure, intensive-timing chemotherapy for acute myeloid leukemia, and acute and chronic graft-versus-host disease. Increasing age, a factor not commonly associated with IFD risk, was identified as a risk factor in multiple published cohorts. CONCLUSIONS: With this systematic review, we have confirmed IFD risk factors that are considered routinely in daily clinical practice. Increasing age should also be considered when assessing patient risk for IFD. Future efforts should focus on defining more precise thresholds for a particular risk factor (ie, age, neutropenia duration) and on development of prediction rules inclusive of individual factors to further refine the risk prediction.

Antifungal stewardship considerations for adults and pediatrics.

Antifungal stewardship refers to coordinated interventions to monitor and direct the appropriate use of antifungal agents in order to achieve the best clinical outcomes and minimize selective pressure and adverse events. Antifungal utilization has steadily risen over time in concert with the increase in number of immunocompromised adults and children at risk for invasive fungal infections (IFI). Challenges in diagnosing IFI often lead to delays in treatment and poorer outcomes. There are also emerging data linking prior antifungal exposure and suboptimal dosing to the emergence of antifungal resistance, particularly for Candida. Antimicrobial stewardship programs can take a multi-pronged bundle approach to ensure suitable prescribing of antifungals via post-prescription review and feedback and/or prior authorization. Institutional guidelines can also be developed to guide diagnostic testing in at-risk populations; appropriate choice, dose, and duration of antifungal agent; therapeutic drug monitoring; and opportunities for de-escalation and intravenous-to-oral conversion.

Galactomannan, ß-D-Glucan, and Polymerase Chain Reaction-Based Assays for the Diagnosis of Invasive Fungal Disease in Pediatric Cancer and Hematopoietic Stem Cell Transplantation: A Systematic Review and Meta-Analysis.

We systematically reviewed and analyzed the available data for galactomannan (GM), ß-D-glucan (BG), and polymerase chain reaction (PCR)-based assays to detect invasive fungal disease (IFD) in patients with pediatric cancer or undergoing hematopoietic stem cell transplantation when used as screening tools during immunosuppression or as diagnostic tests in patients presenting with symptoms such as fever during neutropenia (FN). Of 1532 studies screened, 25 studies reported on GM (n = 19), BG (n = 3), and PCR (n = 11). All fungal biomarkers demonstrated highly variable sensitivity, specificity, and positive predictive values, and these were generally poor in both clinical settings. GM negative predictive values were high, ranging from 85% to 100% for screening and 70% to 100% in the diagnostic setting, but failure to identify non-Aspergillus molds limits its usefulness. Future work could focus on the usefulness of combinations of fungal biomarkers in pediatric cancer and HSCT.

Central Venous Catheter Retention and Mortality in Children With Candidemia: A Retrospective Cohort Analysis.

BACKGROUND: 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. METHODS: A retrospective cohort study of inpatients <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. RESULTS: 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). CONCLUSIONS: 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.

A Prospective, International Cohort Study of Invasive Mold Infections in Children.

BACKGROUND: Invasive mold infections (IMIs) are a leading cause of mortality in immunocompromised children, yet there has never been an international epidemiologic investigation of pediatric IMIs. METHODS: This international, prospective cohort study was performed to characterize the epidemiology, antifungal therapy, and outcomes of pediatric IMIs. Children (≤18 years) with proven or probable IMIs were enrolled between August 2007 and May 2011 at 22 sites. Risk factors, underlying diagnoses, and treatments were recorded. Outcomes were assessed at 12 weeks after diagnosis using European Organization for Research and Treatment of Cancer/Mycoses Study Group response criteria. RESULTS: One hundred thirty-one pediatric patients with IMIs were enrolled; the most common IMI was invasive aspergillosis ([IA] 75%). Children with IA and those with other types of IMIs had similar underlying risk factors, except that children with IMIs caused by non-Aspergillus species were more likely to have received mold-active antifungal agents preceding diagnosis. The most commonly used antifungal classes after diagnosis were triazoles (82%) and polyenes (63%). Combination therapy was used in 53% of patients. Use of combination therapy was associated with an increased risk of adverse events (risk ratio, 1.98; 95% confidence interval, 1.06-3.68; P = .031), although there was no detectable difference in outcome. CONCLUSIONS: Although risk factors for IMIs are similar across specific subtypes, preceding antifungal therapy may be an important modifier. Combination antifungal therapy requires further study to determine its true risks and benefits.

Bronchoalveolar lavage and lung biopsy in patients with cancer and hematopoietic stem-cell transplantation recipients: a systematic review and meta-analysis.

PURPOSE: The objective of this study was to describe the diagnostic yield and complication rate of bronchoalveolar lavage (BAL) and lung biopsy in the evaluation of pulmonary lesions in patients with cancer and recipients of hematopoietic stem-cell transplantation (HSCT). METHODS: We conducted a systematic literature review and performed electronic searches of Ovid MEDLINE, EMBASE, and Cochrane Central Register of Controlled Trials. Studies were included if patients had cancer or were recipients of HSCT, and if they underwent BAL or lung biopsy for the evaluation of pulmonary lesions. Only English language publications were included. RESULTS: In all, 14,148 studies were screened; 72 studies of BAL and 31 of lung biopsy were included. The proportion of procedures leading to any diagnosis was similar by procedure type (0.53 v 0.54; P = .94) but an infectious diagnosis was more common with BAL compared with lung biopsy (0.49 v 0.34; P < .001). Lung biopsy more commonly led to a noninfectious diagnosis (0.43 v 0.07; P < .001) and was more likely to change how the patient was managed (0.48 v 0.31; P = .002) compared with BAL. However, complications were more common with lung biopsy (0.15 v 0.08; P = .006), and procedure-related mortality was four-fold higher for lung biopsy (0.0078) compared with BAL (0.0018). CONCLUSION: BAL may be the preferred diagnostic modality for the evaluation of potentially infectious pulmonary lesions because of lower complication and mortality rates; thus, choice of procedure depends on clinical suspicion of infection. Guidelines to promote consistency in the approach to the evaluation of lung infiltrates may improve clinical care of patients.

Clinician adherence to recommendations for screening of adolescents for sexual activity and sexually transmitted infection/human immunodeficiency virus.

OBJECTIVES: To evaluate clinician adherence to guidelines for documentation of sexual history and screening for sexually transmitted infection (STI)/HIV infection during routine adolescent well visits. Secondary objectives were to determine patient and clinician factors associated with sexual history documentation and STI/HIV testing. STUDY DESIGN: Retrospective, cross-sectional study of 1000 randomly selected 13- to 19-year-old routine well visits at all 29 pediatric primary care practices affiliated with a children's hospital. We evaluated frequency of documentation of sexual history and testing for gonorrhea (GC)/chlamydia (CT) and HIV testing. Multivariable logistic regression was performed to identify factors associated with documentation and testing. RESULTS: Of the 1000 patient visits reviewed, 212 (21.2%; 95% CI, 18.7-23.7) had a documented sexual history, of which 45 adolescents' (21.2%; 95% CI, 15.7-26.8) encounters were documented as being sexually active. Overall, 26 (2.6%; 95% CI, 1.6-3.6) patients were tested for GC/CT and 16 (1.6%; 95% CI, 0.8-2.4) were tested for HIV infection. In multivariable analyses, factors associated with sexual history documentation included older patient age, non-Hispanic black race/ethnicity, nonprivate insurance status, and care by female clinician. Factors associated with GC/CT testing included male gender, non-Hispanic black race/ethnicity, and nonprivate insurance. HIV testing was more likely to be performed on older adolescents, those of non-Hispanic black race/ethnicity, and those with nonprivate insurance. CONCLUSIONS: Pediatric primary care clinicians infrequently document sexual histories and perform STI and HIV testing on adolescent patients. Future studies should investigate provider beliefs, clinical decision-making principles, and perceived barriers to improve the sexual health care of adolescents and evaluate interventions to increase rates of adolescent sexual health screening.

Outcome of pediatric acute myeloid leukemia patients receiving intensive care in the United States.

OBJECTIVE: Children with acute myeloid leukemia are at risk for sepsis and organ failure. Outcomes associated with intensive care support have not been studied in a large pediatric acute myeloid leukemia population. Our objective was to determine hospital mortality of pediatric acute myeloid leukemia patients requiring intensive care. DESIGN: Retrospective cohort study of children hospitalized between 1999 and 2010. Use of intensive care was defined by utilization of specific procedures and resources. The primary endpoint was hospital mortality. SETTING: Forty-three children's hospitals contributing data to the Pediatric Health Information System database. PATIENTS: Patients who are newly diagnosed with acute myeloid leukemia and who are 28 days through 18 years old (n = 1,673) hospitalized any time from initial diagnosis through 9 months following diagnosis or until stem cell transplant. A reference cohort of all nononcology pediatric admissions using the same intensive care resources in the same time period (n = 242,192 admissions) was also studied. INTERVENTIONS: None. MEASUREMENTS AND MAIN RESULTS: One-third of pediatric patients with acute myeloid leukemia (553 of 1,673) required intensive care during a hospitalization within 9 months of diagnosis. Among intensive care admissions, mortality was higher in the acute myeloid leukemia cohort compared with the nononcology cohort (18.6% vs 6.5%; odds ratio, 3.23; 95% CI, 2.64-3.94). However, when sepsis was present, mortality was not significantly different between cohorts (21.9% vs 19.5%; odds ratio, 1.17; 95% CI, 0.89-1.53). Mortality was consistently higher for each type of organ failure in the acute myeloid leukemia cohort versus the nononcology cohort; however, mortality did not exceed 40% unless there were four or more organ failures in the admission. Mortality for admissions requiring intensive care decreased over time for both cohorts (23.7% in 1999-2003 vs 16.4% in 2004-2010 in the acute myeloid leukemia cohort, p = 0.0367; and 7.5% in 1999-2003 vs 6.5% in 2004-2010 in the nononcology cohort, p < 0.0001). CONCLUSIONS: Pediatric patients with acute myeloid leukemia frequently required intensive care resources, with mortality rates substantially lower than previously reported. Mortality also decreased over the time studied. Pediatric acute myeloid leukemia patients with sepsis who required intensive care had a mortality comparable to children without oncologic diagnoses; however, overall mortality and mortality for each category of organ failure studied was higher for the acute myeloid leukemia cohort compared with the nononcology cohort.

Identifying targets for antimicrobial stewardship in children's hospitals.

OBJECTIVE: Antimicrobial stewardship programs (ASPs) are recommended to optimize antimicrobial use for hospitalized patients. Although mechanisms for the implementation of ASPs have been described, data-driven approaches to prioritize specific conditions and antimicrobials for intervention have not been established. We aimed to develop a strategy for identifying high-impact targets for antimicrobial stewardship efforts. DESIGN: Retrospective cross-sectional study. SETTING AND PATIENTS: Children admitted to 32 freestanding children's hospitals in the United States in 2010. METHODS: We identified the conditions with the largest proportional contribution to the total days of antibiotic therapy prescribed to all hospitalized children. For the 4 highest-using conditions, we examined variability between hospitals in antibiotic selection patterns for use of either first- or second-line therapies depending on the condition. Antibiotic use was determined using standardized probability of exposure to selected agents and standardized days of therapy per 1,000 patient-days, adjusting for patient demographics and severity of illness. RESULTS: In 2010, 524,364 children received 2,082,929 days of antibiotic therapy. Surgical patients received 43% of all antibiotics. The 4 highest-using conditions-pneumonia, appendicitis, cystic fibrosis, and skin and soft-tissue infection-represent 1% of all conditions yet accounted for more than 10% of all antibiotic use. Wide variability in antibiotic use occurred for 3 of these 4 conditions. CONCLUSIONS: Antibiotic use in children's hospitals varied broadly across institutions when examining diagnoses individually and adjusting for severity of illness. Identifying conditions with both frequent and variable antimicrobial use informs the prioritization of high-impact targets for future antimicrobial stewardship interventions.

The effect of a hospital-wide urine culture screening intervention on the incidence of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella species.

OBJECTIVE: Optimal strategies for limiting the transmission of extended-spectrum ß-lactamase-producing Escherichia coli and Klebsiella spp (ESBL-EK) in the hospital setting remain unclear. The objective of this study was to evaluate the impact of a urine culture screening strategy on the incidence of ESBL-EK. DESIGN: Prospective quasi-experimental study. SETTING: Two intervention hospitals and one control hospital within a university health system from 2005 to 2009. PATIENTS AND INTERVENTION: All clinical urine cultures with E. coli or Klebsiella spp were screened for ESBL-EK. Patients determined to be colonized or infected with ESBL-EK were placed in a private room with contact precautions. The primary outcome of interest was nosocomial ESBL-EK incidence in nonurinary clinical cultures (cases occurring more than 48 hours after admission). Changes in monthly ESBL-EK incidence rates were evaluated with mixed-effects Poisson regression models, with adjustment for institution-level characteristics (eg, total admissions). RESULTS: The overall incidence of ESBL-EK increased from 1.42/10,000 patient-days to 2.16/10,000 patient-days during the study period. The incidence of community-acquired ESBL-EK increased nearly 3-fold, from 0.33/10,000 patient-days to 0.92/10,000 patient-days (P < .001). On multivariable analysis, the intervention was not significantly associated with a reduction in nosocomial ESBL-EK incidence (incidence rate ratio, 1.38 [95% confidence interval, 0.83-2.31]; P - .21). CONCLUSIONS: Universal screening of clinical urine cultures for ESBL-EK did not result in a reduction in nosocomial ESBL-EK incidence rates, most likely because of increases in importation of ESBL-EK cases from the community. Further studies are needed on elucidating optimal infection control interventions to limit spread of ESBL-producing organisms in the hospital setting.

Pediatric Risk Factors for Candidemia Secondary to Candida glabrata and Candida krusei Species.

This 13-year retrospective study investigated risk factors for candidemia secondary to Candida species with increased likelihood of fluconazole resistance. Of 344 candidemia cases, 23 were caused by C glabrata or C krusei (CGCK). Age >2 years, recent fluconazole exposure, and recent surgery were independent risk factors for CGCK.

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.

Galactomannan Antigen Testing for Diagnosis of Invasive Aspergillosis in Pediatric Hematology Patients.

OBJECTIVE: Invasive aspergillosis (IA) can cause significant morbidity and mortality in immunocompromised children. The galactomannan (GM) enzyme immunoassay (EIA) has been shown in adult studies to be a useful adjunct in diagnosing IA. Data on this assay in children are limited by small sample sizes and conflicting results; false-positive assays were a concern in historical studies. We sought to evaluate the GM EIA in a large cohort of children who received intensive chemotherapy and/or hematopoietic stem cell transplant. A focus was placed on evaluating the assay specificity, and the potential of measuring GM antigen in urine. METHODS: A multicenter prospective observational study in children with anticipated prolonged neutropenia was performed. Serum specimens were collected twice weekly, and urine was collected once weekly during neutropenic periods. Operating characteristics were calculated using the GM EIA optical density index cutoffs of 0.5 and 1.0 for both serum and urine specimens. RESULTS: At least one serum or urine specimen was tested from 198 patients. Ten patients had one or more repeatedly positive serum specimens, while 37 patients had one or more repeatedly positive urine specimens. The specificity of serum and urine testing was 95% and 80%, respectively. Although the urine test resulted in a higher false positivity rate, it successfully identified the only case of probable IA. CONCLUSIONS: Data suggest that the serum GM EIA does not provide frequent false-positive results as previously reported. Screening for galactomannan, or a related antigen in urine, needs to be further evaluated as it may be amenable to development of surveillance strategies.

Trends in zygomycosis in children.

Zygomycosis, or mucormycosis, is associated with significant morbidity and mortality in both children and adults. Studies in adults have shown an increase in the incidence of zygomycosis, particularly among haemtopoietic stem cell transplant (HSCT) recipients and patients with haematologic malignancies. There is a paucity of data on the epidemiology of zygomycosis in children. We performed a retrospective analysis to describe trends in zygomycosis between 1 January 2003 and 31 December 2010. We used the Pediatric Health Information System (PHIS) database to identify paediatric patients who were diagnosed with zygomycosis during the study period. Administrative data on diagnoses, demographics, underlying conditions and clinical experiences were collected. Summary statistics were calculated and tests for trend were conducted. We identified 156 unique patients with zygomycosis. The prevalence of zygomycosis did not significantly increase over time (P=0.284). The most common underlying condition was malignancy (58%) and over half received intensive care. Voriconazole utilisation among all hospitalised children significantly increased during the period (P=0.010). Our study demonstrates that the incidence of zygomycosis is not significantly increasing. During the time period there was a significant increase in the use of voriconazole among children.

Antifungal prophylaxis in pediatric hematology/oncology: new choices & new data.

A severe complication of the treatment of pediatric cancers is the development of an invasive fungal infection (IFI). The data to support antifungal prophylaxis in pediatric oncology patients derive primarily from adult patients, and thus the optimal agent to utilize is not clear. Fluconazole has been a standard option, but agents with antimold activity are now available, each with limitations. Pediatric dosing for voriconazole and posaconazole is uncertain and multiple drug interactions exist. The echinocandins are well-tolerated, but only available in intravenous form. Ultimately, studies demonstrating biologic risk factors for the development of IFI may lead to personalized prophylactic strategies.

Epidemiology and potential preventative measures for viral infections in children with malignancy and those undergoing hematopoietic cell transplantation.

In pediatric patients with malignancy and those receiving hematopoietic stem cell transplants, bacterial and fungal infections have been the focus of fever and neutropenia episodes for decades. However, improved diagnostic capabilities have revealed viral pathogens as a significant cause of morbidity and mortality. Because of limited effective antiviral therapies, prevention of viral infections is paramount. Pre-exposure and post-exposure prophylaxis and antiviral suppressive therapeutic approaches are reviewed. Additionally, infection control practices specific to this patient population are discussed. A comprehensive approach utilizing each of these can be effective at reducing the negative impact of viral infections.