Haemophilus influenzae plays a major role in invasive bacterial infections. Resistant strains are emerging, prompting the WHO to include H. influenzae on its list of priority pathogens for research and development of new antibiotics. We aimed to describe the serotypes, demographics and susceptibility profiles of invasive strains collected in Belgium. Data on invasive strains referred to the Belgian National Reference Center for H. influenzae from 2018 to 2022 were analyzed retrospectively. A total of 608 invasive strains were included. The number of notifications per year ranged from 85 to 165, with a marked decrease between 2020 and 2021. The highest incidence rate was observed in Brussels (1.56 per 100,000 inhabitants over the five year 2018-2022). Sex and age distribution were in line with global trends, as was the predominance of the non-typeable H. influenzae (NTHI). Beta-lactam resistance varies between molecules: 18.9% for ampicillin, 5.6% for amoxicillin-clavulanate. Mutations in the ftsI gene associated with decreased susceptibility to beta-lactams increased from 11.5 to 17.7% over the period studied. The COVID-19 pandemic significantly influenced the epidemiology of invasive H. influenzae infections in Belgium. Demographic analysis identified a significant male predominance among infants, with a male-to-female ratio of 2.57 in patients under one year of age, a high figure not previously reported in the literature. The continued predominance of NTHI underscores the efficacy of Hib vaccination, although the emergence of Hib in patients younger than five years in 2022 suggests an alarming serotype dynamic. The detection of meropenem resistance also highlights the growing threat of antimicrobial resistance, while the increase in ftsI gene mutations raises concerns about the efficacy of first-line treatment. This study provides a comprehensive overview of the epidemiology of invasive H. influenzae infections in Belgium, focusing on demographic changes, serotype predominance and antimicrobial resistance trends. Vigilant surveillance and research are essential to address emerging challenges and guide future interventions, including potential vaccine development.
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