AUTHOR=Slotved Hans-Christian , Johannesen Thor Bech , Stegger Marc , Dalby Tine , Fuursted Kurt 

TITLE=National Danish surveillance of invasive clinical Haemophilus influenzae isolates and their resistance profile

JOURNAL=Frontiers in Microbiology

VOLUME=14

YEAR=2023

URL=https://www.frontiersin.org/journals/microbiology/articles/10.3389/fmicb.2023.1307261

DOI=10.3389/fmicb.2023.1307261

ISSN=1664-302X

ABSTRACT=<sec id="sec1"><title>Introduction</title><p>This study aimed to investigate the epidemiology, serotype distribution, phenotypical antibiogram, and molecular resistance gene characteristics of invasive <italic>Haemophilus influenzae</italic> infections in Denmark from 2014 to 2022. Additionally, the potential impact of outdoor temperature and COVID-19 restrictions on the epidemiology of <italic>H. influenzae</italic> was assessed.</p></sec><sec id="sec2"><title>Materials and methods</title><p>Invasive <italic>H. influenzae</italic> isolates were received from patients with positive culture results from cerebrospinal fluid, blood, or other sterile sites. Sample data were obtained from the Danish laboratory surveillance system/MiBa database, and whole-genome sequencing (WGS) was performed on the isolates. The incidence rates and distribution of <italic>H. influenzae</italic> cases were analyzed, and antibiotic susceptibility were assessed.</p></sec><sec id="sec3"><title>Results</title><p>A total of 1,007 invasive <italic>H. influenzae</italic> cases were identified, with serotyping conducted for 752 (74.7%) isolates. The median incidence per year of <italic>H. influenzae</italic> was 2.0 cases per 100,000, with the highest incidence in 2014 and the lowest in 2020. The majority of <italic>H. influenzae</italic> isolates were non-typeable <italic>H. influenzae</italic> (NTHi), while the most prominent serotypes were serotype f followed by serotype b. Bacteremia cases accounted for the majority (88.6%) of occurrences, although meningitis cases showed an increasing trend during the time period. The age group 85+ exhibited the highest incidence. The implementation of COVID-19 preventive interventions in 2020 resulted in a significant reduction in <italic>H. influenzae</italic> incidence, which returned to pre-COVID levels in 2021. A negative correlation was observed between monthly <italic>H. influenzae</italic> cases and outdoor temperature. An overall level of genetic beta-lactamase resistance of 26.3% was observed divided into 10.6% beta-lactamase-positive ampicillin-resistant (gBLPAR), 13.6% beta-lactamase-negative ampicillin-resistant (gBLNAR) and 2.1% beta-lactamase-positive amoxicillin clavulanate-resistant (gBLPACR). Other non-beta-lactam resistance traits were detected in 7.6% of isolates (primarily aminoglycoside-modifying enzymes).</p></sec><sec id="sec4"><title>Conclusion</title><p>The overall incidence of <italic>H. influenzae</italic> in Denmark returned to stable levels after the COVID-19 epidemic, with NTHi strains dominating. The COVID-19 preventive interventions led to a major reduction in incidence. A significant negative correlation between the incidence of <italic>H. influenzae</italic> and temperature was observed. The study revealed an overall genetic beta-lactam resistance rate of 26.3%, and the concordance between genotypic and phenotypic beta-lactam resistance was high (98.2%).</p></sec>