Epidemiology and Antifungal Susceptibility of Bloodstream Fungal Isolates in Pediatric Patients: a Spanish Multicenter Prospective Survey

Abstract

Data on fungemia epidemiology and antifungal susceptibility of isolates from children are scarce, leading frequently to pediatric empirical treatment based on available adult data. The present study was designed to update the epidemiological, mycological, and in vitro susceptibility data on fungal isolates from children with fungemia in Spain. All fungemia episodes were identified prospectively by blood culture over 13 months at 30 hospitals. Tests of susceptibility to amphotericin B, flucytosine, fluconazole, itraconazole, posaconazole, voriconazole, anidulafungin, caspofungin, and micafungin were performed at participant institutions by a microdilution colorimetric method. New species-specific clinical breakpoints for fluconazole, voriconazole, and echinocandins were also applied. A total of 203 episodes of fungemia in 200 children were identified. A higher proportion of fungal isolates was from general wards than intensive care units (ICU). Candida parapsilosis (46.8%), Candida albicans (36.5%), Candida tropicalis (5.9%), Candida glabrata (3.9%), and Candida guilliermondii (2.5%) were the leading species. C. parapsilosis was the predominant species except in neonates. C. albicans was the most frequent in neonatal ICU settings (51.9%). Intravascular catheter (79.3%), surgery (35%), prematurity (30%), and neutropenia (11%) were the most frequent predisposing factors. Most Candida isolates (95.1%) were susceptible to all antifungals. When the new species-specific clinical breakpoints were applied, all C. parapsilosis isolates were susceptible to echinocandins except one, which was micafungin resistant. This is the largest published series of fungemia episodes in the pediatric setting. C. parapsilosis is the most prevalent species in Spain, followed by C. albicans and C. tropicalis. Resistance to azole and echinocandin agents is extremely rare among Candida species. The fluconazole resistance rate in Spain has decreased in the last 10 years.

Effect of an intervention to improve the prescription of antifungals in pediatric hematology‐oncology

“…Studies in adult population reveal that AFS programs are also efficacious and cost‐effective, without reducing the quality of care, but studies regarding AFS in childhood population are scarce. Conversely, antifungal misuse entails specific challenges in pediatrics, including high case‐fatality rates, high costs, random drug pharmacokinetics, adverse events and interactions, and potential emergence of antifungal resistance . Therefore, it is of utmost importance to establish pediatric‐based strategies in order to ensure optimal antifungal prescription to this vulnerable population.…”

Epidemiology and risk factors for invasive candidiasis

“…Similarly, in Sweden and Switzerland, the ratio of C. albicans is above 60% and followed by C. glabrata 17,38. However, in Spain the ratio of C. albicans is below 50% and the most common non- albicans Candida species is C. parapsilosis 20,21,61. Likewise, in another Mediterranean country, Italy, C. albicans is responsible for almost 50% of the IC cases and followed by C. parapsilosis 22,46.…”

Candidemia in Children Caused by Uncommon Species of Candida

“…Generally, C. glabrata candidemia is difficult to manage, and high mortality is seen (3). Nevertheless, since that is very infrequent in the pediatric setting, fluconazole is a logical choice for candidemia treatment before species identification, except in children with prior azole exposure (16).…”