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Amphotericin B in Pediatrics: Analysis by Age Stratification Suggests a Greater Chance of Adverse Events from 13 Months of Age Onwards

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Abstract

Background and Objective

Amphotericin B deoxycholate (AMB-D) remains an antifungal agent with great therapeutic value in pediatric patients. The currrent consensus is that its use in neonates is safer than in older children. However, childhood presents different periods of development that deserve to be evaluated more precisely. Our goal was to assess the usage profile of AMB-D in stratified pediatric age groups, adapted according to the National Institute of Child Health and Human Development classification.

Methods

This retrospective cross-sectional observational study was conducted at a Brazilian tertiary children’s hospital between January 2014 and December 2019.  Data of patients who received at least two doses of intravenous AMB-D while hospitalized were extracted from electronic health files. Information on patient demographics, underlying diseases and comorbidities, laboratory examinations, fungal infection diagnosis, and AMB-D use were gathered following specific criteria. Nonparametric tests were applied, such as the chi-square test to compare proportions and Fisher’s exact test to assess the association between categorical variables or contingency tables.

Results

One hundred and twenty-seven (127) medical records were stratified as preterm neonatal (birth <37 weeks postmenstrual age), term neonatal (birth–27 days), infants (28 days–12 months), toddlers (13 months–2 years), early childhood (3–5 years), middle childhood (6–11 years), and early adolescence (12–18 years). The criteria for the indication of AMB-D followed empirical use as the main indication (n = 74; 58.26%), proven and probable fungal infection (n = 39; 30.71%), and medical suspicion (n = 14; 11.02%). Candida spp. was the main etiologic agent isolated in cultures, with the highest frequency of C. albicans (n = 18; 40%), followed by Candida parapsilosis (n = 14; 31.11%), and Candida tropicalis (n = 6; 13.33%). Very few acute infusion-related adverse effects were observed during the administration of AMB-D in pediatric patients. We found an unfavorable impact of AMB-D use in patients from 13 months of age onwards suggesting this group as a turning point for a greater chance of adverse events, and not soon after the neonatal period.

Conclusions

Clinical or observational studies based on age stratification are essential to accurately elucidate whether potentially toxic drugs can be used safely in the pediatric population. Our search for a turning point was shown to contribute to the accuracy of the study, as it provided data on the impact of D-AMB in specific pediatric age groups.

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Authors and Affiliations

  1. Postgraduate Program in Internal Medicine and Health Sciences, Federal University of Paraná (UFPR), 181, General Carneiro Street, Curitiba, Brazil

    Francelise Bridi Cavassin

  2. Faculdades Pequeno Príncipe, Curitiba, Brazil

    João Luiz Baú-Carneiro

  3. Hospital Pequeno Príncipe, Curitiba, Brazil

    Fabio de Araújo Motta

  4. Faculdades Pequeno Príncipe (FPP), Curitiba, Brazil

    Ana Paula Matzenbacher Ville & Leticia Staszczak

  5. Department of Public Health, Hospital de Clínicas, Federal University of Paraná (HC-UFPR), Curitiba, Brazil

    Flávio de Queiroz-Telles

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  1. Francelise Bridi Cavassin
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  3. Fabio de Araújo Motta
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  6. Flávio de Queiroz-Telles
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Corresponding author

Correspondence to Francelise Bridi Cavassin.

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The authors received no specific funding for this work.

Conflict of Interest/Competing Interests

FBC, JLB-C, FdAM, APMV, LS, and FdQ-T have no conflicts of interest that are directly relevant to the content of this article.

Ethics Approval

Ethical approval was granted by the Ethics Committee of Hospital Pequeno Príncipe with the waiver of the consent form due to the retrospective nature of the study and the fact that the data collection form is part of the routine of care. Ethical approval number: 3,803,746.

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The datasets generated during and/or analyzed during the current study are available from the corresponding author upon reasonable request.

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Authors’ Contributions

All authors contributed to the study conception and design. Material preparation, data collection, and analysis were also performed by all authors. The first draft of the manuscript was written by FBC and all authors commented on previous versions of the manuscript. All authors read and approved the final manuscript.

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Cavassin, F.B., Baú-Carneiro, J.L., de Araújo Motta, F. et al. Amphotericin B in Pediatrics: Analysis by Age Stratification Suggests a Greater Chance of Adverse Events from 13 Months of Age Onwards. Pediatr Drugs 24, 513–528 (2022). https://doi.org/10.1007/s40272-022-00523-0

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