Welcome to the ESPID 2022 Meeting Calendar
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New Developments in Paediatric Antifungal Pharmacology
Fungal Biomarkers in Neonates and Children
INVASIVE MOLD INFECTIONS IN CHRONIC GRANULOMATOUS DISEASE: A SINGLE-CENTER RETROSPECTIVE COHORT
Invasive fungal infections are an important cause of mortality in patients with chronic granulomatous disease (CGD). In this study, we aimed to determine the incidence and the prognosis of invasive mold infections in CGD cases followed in our center.
All CGD cases followed up in the Marmara University School of Medicine, Division of Pediatric Immunology, between 2007 and 2021 were included. Demographic and clinical characteristics, primary antifungal prophylaxis regimen, and if mold-associated invasive fungal infection (mIFI) is seen, the type, treatment, prognosis, and secondary prophylaxis regimen used for mIFI were analyzed retrospectively.
Thirty-one patients with CGD were included.All patients were diagnosed with CGD via the DihydroRodamin test. Twenty-five(80.6%) patients were male. CGD was X-linked in 13 patients and autosomal recessive in 14 patients.The median age at diagnosis of CGD was 51.6(min:2, max:302) months. Allogeneic hematopoietic stem cell transplantation was performed in 5 patients.
Fifteen mIFI attacks were detected in 14 of 31 patients. The type of mIFI was proven in 4, probable in 2, and possible in 8 patients. Median mIFI age was 94.7(min:3,max:331) months. A total of 3 patients died, two of them were due to mIFI. Of those with mIFI, 5(35.8%) were autosomal recessive and 9(64.2%) were X-linked. Ten patients were diagnosed with CGD while investigating the mIFI episode, and mIFI was detected in the other four patients under itraconazole prophylaxis.
In this study, we revealed the overburden of mIFI in our CGD cases.A prophylaxis regimen with an agent with better mold activity can be considered as a measure to reduce the burden of mIFI.The second phase of this study continues on a multicenter basis, as the experience of a single center is insufficient to make this recommendation.
ANTIFUNGAL USE IN EUROPEAN PEDIATRIC INTENSIVE CARE UNITS (PICUS): A 12-WEEK MULTICENTER MODIFIED POINT PREVALENCE STUDY (CALYPSO)
Knowledge of antifungal use in PICUs across Europe, while frequently prescribed, is limited. A 12-wk modified point-prevalence study was conducted to record antifungal use in Εuropean PICUs.
All patients hospitalized in the participating PICUs and receiving systemic antifungals were included. Information about ward demographics was collected once at the beginning; weekly ward and patient data were collected prospectively for the 12-wk study period and entered in REDCap database.
18 PICUs (15 hospitals), in 10 European countries participated. 8/18 (44%) of PICUs followed prophylactic practices for patients with immunocompromise/neutropenia, long-term parenteral nutrition or central lines, 7/18 (39%) had an antifungal stewardship program implemented and the majority (16/18) used biomarkers (15/16 galactomannan, 12/16 each beta-D-glucan and Cryptococcal antigen). 101 patients with ages ≤90d (14 patients), 3-60mo (44pts) and >5yrs (43pts) were recorded. Malignancy was the most common underlying condition among patients aged >90d (28%) followed by surgery/trauma (25%), whereas all patients ≤90d had previous surgery. Indication for antifungal prescribing was prophylaxis in 38% and treatment in 62% [empirical (57%), preemptive (13%) and targeted (30%)]. Fluconazole was the most common agent both for prophylaxis [45%, median dose: 6 (range 2-9) mg/kg/d] and empirical treatment [53%, median dose: 10 (range 1-12) mg/kg/d], whereas LAMB was the most frequent agent for targeted treatment [37%, median dose: 5 (range 3-6) mg/kg/d] (Table 1). Common reasons for empirical and targeted treatment were persistent fever in high-risk patients (58%) and candidiasis (100%), respectively. For targeted treatment, the most frequent pathogens were Candida albicans (37%) and Candida parapsilosis (32%).
The majority of antifungal prescriptions across European PICUs were for prophylaxis or empirical treatment. These data will be valueable for guiding antifungal stewardship strategies in PICUs
ANTIFUNGAL PROPHYLAXIS WITH LIPOSOMAL AMPHOTERICIN B (LAMB) IN PAEDIATRIC PATIENTS WITH ACUTE LYMPHOBLASTIC LEUKAEMIA (ALL) DURING INDUCTION PHASE
LAMB prophylaxis was started for ALL patients during induction chemotherapy in our institution secondary to an increased incidence of IFD (Invasive Fungal Disease). LAMB was chosen in view of the less pharmacological interactions with vincristine and its easy delivery in the community. Our study aimed to review the effectiveness and safety of this measure.
Retrospective single centre descriptive study from April 2019 to April 2020. ALL paediatric patients (<18 years) started on 2.5mg/kg twice a week intravenous LAMB during the induction phase of chemotherapy (UKALL11) were included. Toxicity, allergic/infusion reactions and breakthrough IFDs were recorded.
41 patients were included (23 male). Median age was 4.4 years (IQR 3.3-6.9). Disease profile was: B-ALL (34/41), T-ALL (2/41), Ph-ALL (2/41), ABL fusion (1/41), relapsed ALL(1/41). 38/41 patients received LAMB prophylaxis; for the remaining 3/41, LAMB was early discontinued (two cases due to allergic reactions to the testing dose and one case of possible IFD at day three of induction). A total of 23/38 (60.5%) patients presented deranged (grade 3 or 4) biochemistry results while receiving LAMB prophylaxis: hypokalemia (3/38), deranged ALT (23/38) and hyperbilirubinemia (1/38); no patients presented raised creatinine or hypomagnesemia. Only in one case, toxicity was attributed to LAMB and led to drug discontinuation. A total of 5/41(12%) patients presented allergic/infusion reactions: in three, this led to LAMB discontinuation (2/5 after the test dose and one case during the 4th week of prophylaxis). From the 5/41(12%) cases who had LAMB prophylaxis discontinued, 4 were changed to caspofungin and one started on LAMB treatment.
In our experience prophylactic intravenous LAMB presented a good safety profile. Allergic/infusion reactions wer the main reason for withdrawal. No breakthrough infections were identified.