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 o… Show more
“…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.…”
Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.
“…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.…”
Hematologic side effects are associated with prolonged antibiotic exposure in up to 34% of patients. Neutropenia, reported in 10-15% of patients, increases the risk of sepsis and death. Murine studies have established a link between the intestinal microbiota and normal hematopoiesis. We sought to identify predisposing factors, presence of microbiota-derived metabolites, and changes in intestinal microbiota composition in otherwise healthy pediatric patients who developed neutropenia after prolonged courses of antibiotics. In this multi-center study, patients with infections requiring anticipated antibiotic treatment of two or more weeks were enrolled. Stool samples were obtained at the start and completion of antibiotics and at the time of neutropenia. We identified 10 patients who developed neutropenia on antibiotics and 29 controls matched for age, sex, race, and ethnicity. Clinical data demonstrated no association between neutropenia and type of infection or type of antibiotic used; however intensive care unit admission and length of therapy were associated with neutropenia. Reduced intestinal microbiome richness and decreased abundance of Lachnospiraceae family members correlated with neutropenia. Untargeted stool metabolomic profiling revealed several metabolites that were depleted exclusively in patients with neutropenia, including members of the urea cycle pathway, pyrimidine metabolism and fatty acid metabolism that are known to be produced by Lachnospiraceae. Our study confirms a relationship between intestinal microbiota disruption and abnormal hematopoiesis and identifies taxa and metabolites likely to contribute to microbiota-sustained hematopoiesis. As the microbiome is a key determinant of stem cell transplant and immunotherapy outcomes, these findings are likely to be of broad significance.
“…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.…”
Section: Discussionsupporting
confidence: 89%
“…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.…”
supporting
confidence: 85%
“…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.…”
: Neutropenia is defined as absolute neutrophil count <1500cells/mm. This condition is observed in different situations - from a variant of the normal to life-threatening acquired and congenital diseases. Diseases like Tuberculosis, malaria, pertussis, typhoid, dengue, HIV, etc. can cause neutropenia. Mild cases are usually asymptomatic. But severe cases are extremely susceptible to infections, mainly viral infections like CMV, EBV, HIV, etc. Clinical manifestations, like complications, depend on the severity of neutropenia. The clinical manifestations of isolated neutropenia are diverse, including the frequency of infectious episodes. A thorough infectious history of neutropenic patients is the initial step of the evaluation. : To enlist the causes and clinical features, to document various treatment modalities, and to assess the outcome of children with non-malignant neutropenia. : Hospital based prospective cross-sectional study was conducted for 20 months among 42 patients at Department of Pediatrics of tertiary care Hospital. Study was conducted from February 2021 to August 2022. : Total 20 were males and 22 were females. Among the study participants, 36 were >2 years of age and 6 were <2 years of age had nonmalignant neutropenia. Among the study participants, 40 were from urban area and 2 were from rural area. More number of patients had come with chief complaint of fever. : The current population of children in India is close to 1.41 billion and 10.2% of it suffering from neutropenia makes it an important health problem that needs to be thoroughly evaluated.
“…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.…”
Introduction: Linezolid is an oxazolidinone antibiotic that is active against drug-resistant Gram-positive bacteria and multidrug-resistant Mycobacterium tuberculosis. Real-world studies on the safety of linezolid in large populations are lacking. This study aimed to determine the adverse events associated with linezolid in real-world settings by analyzing data from the US Food and Drug Administration (FDA) Adverse Event Reporting System (FAERS).Methods: We retrospectively extracted reports on adverse drug events (ADEs) from the FAERS database from the first quarter of 2004 to that of 2023. By using disproportionality analysis including reporting odds ratio (ROR), proportional reporting ratio (PRR), Bayesian Confidence Propagation Neural Network (BCPNN), along with the multi-item gamma Poisson shrinker (MGPS), we evaluated whether there was a significant association between linezolid and ADE. The time to onset of ADE was further analyzed in the general population and within each age, weight, reporting population, and weight subgroups.Results: A total of 11,176 reports of linezolid as the “primary suspected” drug and 263 significant adverse events of linezolid were identified, including some common adverse events such as thrombocytopenia (n = 1,139, ROR 21.98), anaemia (n = 704, ROR 7.39), and unexpected signals that were not listed on the drug label such as rhabdomyolysis (n = 90, ROR 4.33), and electrocardiogram QT prolonged (n = 73, ROR 4.07). Linezolid-induced adverse reactions involved 27 System Organ Class (SOC). Gender differences existed in ADE signals related to linezolid. The median onset time of all ADEs was 6 days, and most ADEs (n = 3,778) occurred within the first month of linezolid use but some may continue to occur even after a year of treatment (n = 46).Conclusion: This study reports the time to onset of adverse effects in detail at the levels of SOC and specific preferred term (PT). The results of our study provide valuable insights for optimizing the use of linezolid and reducing potential side effects, expected to facilitate the safe use of linezolid in clinical settings.
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