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

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.

Antibiotic-associated neutropenia is marked by depletion of intestinalLachnospiraceaein pediatric patients

“…We identified associations between neutropenia and the total length of antibiotic therapy, length of intravenous antibiotic therapy, length of admission to the hospital and admission to the intensive care unit (Table 2) . Previous reports concur with the increased risk of neutropenia with longer treatment courses, as we saw in our cohort 33,34 . While standard intravenous and oral dosing for many common antibiotics (e.g.…”

Evaluation of non-malignant neutropenia in children at tertiary care hospital of South Gujarat

“…17 The congenital and cyclic categories are regarded as congenital neutropenia, while the idiopathic and autoimmune categories are acquired. In Present Study, the frequency of Non-Malignant Neutropenia was found to be 0.83% which was slightly lesser but still comparable with other studies like Battini et al (1.91%), 9 Jiunn-Ming Sheen et al (2.16%), 12 Kyriaki Karavanaki et al (2%). 11 Females were more than males, while in other studies of Joanna Konieczek et al, 18 Tschenin et al, 19 and Akanksha Mahajan et al 19 Present Study shows the mean hemoglobin level is 7.8g/dl whereas Vasiliki Vlacha et al 6 and Ozdemir et al 13 have higher mean hemoglobin level.…”

“…85.7% patients belonged to>2 years of age group which is comparable with Nguyen S.N et al10 while in study of Jiunn-Ming Sheen et al12 and Kyriaki Karavanaki et al 11 majority patients were below 1 year of age. In Present Study, mean age of the cases is more than 5 years which is comparable with Vasiliki Vlacha et al6 and Battini et al9 In Nguyen S.N et al,10 Kyriaki Karavanaki et al11 and Jiunn-Ming Sheen et al12 mean age of the cases is less than 5 years.In Present Study, 95.2% patients were residing at urban area, on counterpart, Nguyen S.N et al10 study 33.02% patients were residing at urban area. More cases belonging to urban region in the present study can be because of the urban location of the hospital in tier 2 city.…”

“…Neutropenia is a clinically significant entity due to its association with increased risk of infection. The severity of neutropenia is associated with the susceptibility to 6 8.8 Years Battini et al 9 10 years Nguyen S.N et al 10 25 months Kyriaki Karavanaki et al 11 0.7 years Jiunn-Ming Sheen et al 12 31.3 months pyogenic infection. 15 Additional factors, such as bone marrow myeloid reserves, speed of onset and duration of the neutropenia, absolute monocyte count, and the capacity of phagocytes, influence the susceptibility to infection in neutropenic patients.…”

Adverse drug events associated with linezolid administration: a real-world pharmacovigilance study from 2004 to 2023 using the FAERS database

“…Other studies have reported associations between linezolid and specific side effects using centralized data (Lee and Caffrey, 2018;Dai et al, 2020;Gatti et al, 2021a;Battini et al, 2022;Ni et al, 2022;Shao et al, 2023). This study, for the first time, comprehensively documented and evaluated the safety of post-marketing administration of linezolid based on the largest sample of realworld data to date.…”