Invasive candidiasis is a common and frequently fatal infection in high-risk hospitalized children. Coordinated efforts have improved the prevention and treatment of invasive candidiasis in adult patients, but little work has been done to improve outcomes in children. As a result, practice guidelines addressing the treatment for invasive candidiasis contain limited and poorly validated data for children. This lack of pediatric-specific information is concerning as major differences exist between the two populations. This project will address important questions about the best treatment strategies for children with invasive candidiasis.
Primary Objective: Compare the effectiveness of echinocandin versus amphotericin B or triazole antifungal therapy for pediatric invasive candidiasis.
Secondary Objective: Characterize the frequency of invasive candidiasis in pediatric patients.
Males or females age > 120 days and <18 years
Incident case of proven or probable invasive candidiasis
Invasive candidiasis refers to a positive culture for a Candida species in a normally sterile site: Blood, CSF, bone, implanted devices (e.g. AV graft), vitreous humour, biopsy sites (e.g. lung, pericardium).
Non-sterile sites such as respiratory (BAL, sputum), esophagus, mucosa, GI tract, and skin should not be used for inclusion unless there is additional evidence of invasive disease.
Urine should not solely be used for inclusion as urine cultures can yield Candida in the absence of true infection (e.g. in the presence of a foley catheter). However, if there is further evidence of invasive kidney disease (e.g. radiographic evidence of fungal balls in kidneys), then the patient would be eligible for inclusion.
Parental/guardian permission (informed consent, if required at that site) and, if appropriate, child assent (if required at that site).
Any history of prior Candida infection within the previous 35 days
The IPFN has multiple ongoing research projects dedicated to improving the diagnosis, treatment, and outcomes of pediatric patients with invasive fungal infections.
BIOPIC (BIOmarkers for Pediatric Invasive Candidiasis)
This study will determine if fungal biomarkers can improve the time to diagnosis of invasive candidiasis in high risk pediatric patients as compared to traditional blood cultures. Additionally, these same fungal biomarkers will be evaluated to measure response to antifungal treatment in those high risk patients that develop invasive candidiasis.
We will prospectively enroll 500 patients throughout all International Pediatric Fungal Network (IPFN) sites over 4 years. In order to increase the utility of these biomarkers, we will only enroll pediatric patients who are at “high-risk” for developing candidiasis (defined in inclusion criteria below, and based on previous epidemiologic studies). When an eligible patient has a blood culture drawn for clinical care, he or she will be enrolled and have research blood for biomarker testing drawn as soon as possible. The day that the clinical blood culture is drawn is "Day 0".
Most patients will not go on to develop invasive candidiasis, as defined by the international Mycoses Study Group / European Organization for the Treatment of Cancer (MSG/EORTC) definitions, and will not have any more blood drawn in this study. For those patients that do develop invasive candidiasis, we will also potentially draw study blood for the same biomarker tests on days +5, +7, and +14. This equates to 5, 7, and 14 days after “Day 0”.
Blood for biomarkers will be drawn from patients using the kits and tubes provided by the IPFN.
Inclusion Criteria for initial study enrollment
Males or females age > 120 days and <18 years
Have at least one of the following conditions:
admitted to a non-neonatal ICU with any underlying disease
being imminently transferred to a non-neonatal ICU with any underlying disease
gastro-intestinal insufficiency (e.g., chronic short-gut syndrome) and admitted to anywhere in the hospital
hematologic malignancy (limited to AML, ALL, Non-Hodgkin’s lymphoma, and myelodysplastic syndrome) and admitted to anywhere in the hospital
solid tumor malignancy and admitted to anywhere in the hospital
hematopoietic stem cell or bone marrow transplant and admitted to anywhere in the hospital
aplastic anemia and admitted to anywhere in the hospital
Have ≥ 1 blood culture drawn for clinical concern of infection at time of enrollment
Have ≥ 1 central catheter (arterial or venous)
Clinician initiates and/or changes any systemic antimicrobial therapy at the time of enrollment
Parental/guardian permission (informed consent) and, if appropriate, child assent
Inclusion criteria for subsequent research blood samples:
Patient meets all criteria for initial enrollment, has the initial study blood sample collected, AND is diagnosed with invasive candidiasis according to the international definitions between day 0 and day +14
Diagnosis of possible, probable or proven invasive fungal infection within the 30 days prior to study enrollment
Previous inclusion in this study
Weight < 4 kg (Due to constraints of no more than 3 ml/kg of blood to be drawn over an 8 week period). Subjects that fall below 4 kg during the study period will not have more than 0.75 ml/kg of blood drawn each time.
Patient receiving empiric antifungal therapy for prolonged neutropenia or fever that was started prior to the time that the clinically indicated blood culture was drawn.
If blood cultures are obtained and anti-infectives are added/changed ONLY as part of a local protocol and not driven by clinical concern for infection.
International Pediatric Fungal Network, Box 3499, Duke University Medical Center, Durham, NC 27710. USA. Tel: 919-668-4847 Email:PFNContracts@duke.edu
Information about additional clinical trials for pediatric fungal infections can be found on ClinicalTrials.gov.