Neonatal Antifungal Consumption Is Dominated by Prophylactic Use; Outcomes From The Pediatric Antifungal Stewardship: Optimizing Antifungal Prescription Study

Abstract

AntimicrobiAl reportsBackground: Diagnostic challenges combined with the vulnerability of neonates to develop invasive candidiasis (IC) may lead to antifungal administration in the absence of IC. A modified point-prevalence study was performed to obtain an improved insight and understanding of antifungal prescribing in this specific patient population. Methods: Neonates and infants ≤90 days of age receiving systemic antifungals from 12 centers in England were included. Data were collected prospectively during 26 consecutive weeks and entered into an online REDCap database. Results: Two hundred eighty neonates and infants were included, the majority ≤1 month of age (68.2%). Prematurity was the commonest underlying condition (68.9%). Antifungals were prescribed for prophylactic reason in 79.6%; of those, 64.6% and 76.3% were extreme low birth weight infants and prematurely born neonates, respectively. Additional risk factors were present in almost all patients, but only 44.7% had ≥3 risk factors rendering them more susceptible to develop IC. Nonpremature and non extremely low birth weight premature infants only scored ≥3 risk factors in 32.6% and 15%, respectively. Fluconazole was the most common antifungal used (76.7% of all prescriptions), and commonly underdosed as treatment. The number of microbiologic proven IC was low, 5.4%. Conclusions: Neonatal antifungal prophylaxis is commonly prescribed outside the recommendations based on known risk profiles. Fluconazole is the main antifungal prescribed in neonates and infants, with underdos-ing frequently observed when prescribed for treatment. Number of proven IC was very low. These observations should be taken into consideration to develop a national pediatric Antifungal Stewardship program aiming to guide rational prescribing.

Antifungal stewardship in a tertiary care paediatric hospital: the PROAFUNGI study

“…On the other hand, posaconazole is mainly indicated in the HSCT post-engraftment period and in some primary immunodeficiencies (PID) such as chronic granulomatous disease. These data was quite different from other studies in which fluconazole is the most commonly prescribed agent [7,[11][12][13]. Nonetheless, all these studies include a high proportion, or exclusively include, neonates in whom Candida spp.…”

“…Nonetheless, all these studies include a high proportion, or exclusively include, neonates in whom Candida spp. is the main and almost only fungal pathogen [7,11,12]. Conversely, for paediatric, particularly children with cancer, PID or HSCT (a majority in our cohort), filamentous fungi should be considered, and other AFs with a broader spectrum play a major role [2,10,18,19].…”

“…In contrast, data about paediatric AFS are scant and mainly limited to adult programmes including children or to specific situations such as invasive Candida spp. infection or cancer [7,8].…”

The current state of antifungal stewardship among pediatric antimicrobial stewardship programs

“…For example, studies have shown that up to 50% of antifungals are inadequately dosed and that certain antifungals require multiple dose adjustments to achieve therapeutic levels. 5,28,30,31 Our study revealed variability in the target therapeutic levels reported across institutions, which suggests a lack of consensus in current practices and an important opportunity for standardization. Many of the survey respondents reported a lack of confidence in making antifungal recommendations.…”

“…26,27 However, fluconazole may represent an important antifungal stewardship target because it accounts for~70% of antifungal prescriptions in children 4 and has been associated with inappropriate prescribing in neonates and children. 1,28 The TDM of azole medications is an important strategy to ensure the appropriate use of antifungals and mitigate adverse events. 29 Most institutions responding to this survey routinely monitor azole levels; however, TDM was the least commonly monitored parameter among ASPs performing PAF of antifungals, and only a few institutions reported having a pharmacokinetics program to assist with antifungal TDM.…”