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. 2022 Jun 2:13:877932.
doi: 10.3389/fphar.2022.877932. eCollection 2022.

Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review

Vera Battini  1 , Alessandra Mari  2 , Michele Gringeri  1 , Francesca Casini  2 , Francesco Bergamaschi  2 , Giulia Mosini  1 , Greta Guarnieri  1 , Marco Pozzi  3 , Maria Nobile  3 , Gianvincenzo Zuccotti  2 , Emilio Clementi  1   3 , Sonia Radice  1 , Valentina Fabiano  2 , Carla Carnovale  1
Affiliations

Antibiotic-Induced Neutropenia in Pediatric Patients: New Insights From Pharmacoepidemiological Analyses and a Systematic Review

Vera Battini et al. Front Pharmacol. .

Abstract

Aim: to characterize pediatric cases of antibiotic-associated neutropenia through a multidisciplinary approach, focusing on the temporal association between the wide spectrum of treatment options and the occurrence of this relatively uncommon but potentially clinically relevant adverse event. Methods: we carried out a pharmacoepidemiological analysis based on the FDA Adverse Event Reporting System (FAERS) database, a retrospective chart review and a systematic review of the literature, focusing on the time to onset (TTO) of this side effect, in the pediatric clinical setting. Results: A total of 281 antibiotic-related neutropenia events, involving 11 categories of antibiotics, were included in the time to onset analysis. The median TTO ranged from 4 to 60 days after the start of the therapy. A shorter median TTO was found from the retrospective chart review [16 patients: median days (25th-75th percentiles) = 4 (3-5)], compared to 15 (9-18) vs. 10 (6-18) for literature (224 patients) and FAERS (41 cases), respectively. The Anatomical Therapeutic Chemical classes, J01X, J01F, J01E and J04A, and the median TTOs retrieved from more than one source revealed high accordance (p > 0.05), with J01X causing neutropenia in less than a week and J01F/J01E/J04A in more than 10 days. Antibiotics were discontinued in nearly 34% of cases. In FDA Adverse Event Reporting System reports, half of the patients experiencing neutropenia were hospitalized. Conclusion: Whereas antibiotic associated neutropenia is benign in the majority of cases, yet it should not be neglected as, even if rarely, it may put children at higher risk of clinical consequences. Clinicians' awareness of antibiotic-associated neutropenia and its mode of presentation contributes to the continuous process of monitoring safety of antibiotics.

Keywords: FAERS; antibiotics; neutropenia; pediatrics; pharmacovigilance.

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Conflict of interest statement

The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest.

Figures

FIGURE 1
FIGURE 1
The median of the pre-and post-therapy neutrophils (%, n/mmc) and WBC levels (n/mmc).
FIGURE 2
FIGURE 2
The PRISMA flowchart.
See this image and copyright information in PMC

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