Table_1_National Danish surveillance of invasive clinical Haemophilus influenzae isolates and their resistance profile.docx

IntroductionThis study aimed to investigate the epidemiology, serotype distribution, phenotypical antibiogram, and molecular resistance gene characteristics of invasive Haemophilus influenzae infections in Denmark from 2014 to 2022. Additionally, the potential impact of outdoor temperature and COVID-19 restrictions on the epidemiology of H. influenzae was assessed.Materials and methodsInvasive H. influenzae 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 H. influenzae cases were analyzed, and antibiotic susceptibility were assessed.ResultsA total of 1,007 invasive H. influenzae cases were identified, with serotyping conducted for 752 (74.7%) isolates. The median incidence per year of H. influenzae was 2.0 cases per 100,000, with the highest incidence in 2014 and the lowest in 2020. The majority of H. influenzae isolates were non-typeable H. influenzae (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 H. influenzae incidence, which returned to pre-COVID levels in 2021. A negative correlation was observed between monthly H. influenzae 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).ConclusionThe overall incidence of H. influenzae 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 H. influenzae 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%).

引言本研究旨在探讨2014年至2022年期间丹麦侵袭性流感嗜血杆菌感染的流行病学、血清型分布、表型抗生素敏感谱以及分子耐药基因特征。此外，还评估了户外温度和COVID-19限制措施对流感嗜血杆菌流行病学的影响。
材料与方法来自脑脊液、血液或其他无菌部位的阳性培养结果的侵袭性流感嗜血杆菌分离株被收集。样本数据来源于丹麦实验室监测系统/MiBa数据库，并对分离株进行了全基因组测序（WGS）。分析了流感嗜血杆菌病例的发病率及其分布，并评估了抗生素敏感性。
结果共确定了1,007例侵袭性流感嗜血杆菌病例，对752（74.7%）分离株进行了血清型鉴定。流感嗜血杆菌的年发病率中位数为每10万人2.0例，2014年发病率最高，2020年最低。大多数流感嗜血杆菌分离株为不可分型的流感嗜血杆菌（NTHi），其中最显著的血清型为f型，其次是b型。菌血症病例占病例总数的多数（88.6%），尽管在此期间脑膜炎病例呈上升趋势。85岁以上的年龄组发病率最高。2020年实施的COVID-19预防干预措施导致流感嗜血杆菌发病率显著下降，2021年回升至COVID-19前的水平。观察到流感嗜血杆菌病例数与户外温度呈负相关。观察到整体遗传性β-内酰胺酶耐药率为26.3%，分为10.6%的β-内酰胺酶阳性阿莫西林耐药（gBLPAR）、13.6%的β-内酰胺酶阴性阿莫西林耐药（gBLNAR）和2.1%的β-内酰胺酶阳性阿莫西林克拉维酸耐药（gBLPACR）。在7.6%的分离株中检测到其他非β-内酰胺耐药特征（主要为氨基糖苷类修饰酶）。
结论丹麦的流感嗜血杆菌总体发病率在COVID-19疫情后恢复至稳定水平，NTHi菌株占据主导地位。COVID-19预防干预措施导致了发病率的显著降低。观察到流感嗜血杆菌发病率与温度之间呈显著负相关。研究揭示了整体遗传性β-内酰胺酶耐药率为26.3%，且基因型和表型β-内酰胺酶耐药性之间的一致性很高（98.2%）。