Epidemiology and population structure of Haemophilus influenzae causing invasive disease

Since the inclusion of H. influenzae in the WHO watch list, monitoring of circulating serotypes and the level of resistance to ß-lactams has become crucial. This study provides an epidemiological update on invasive H. influenzae disease at Bellvitge University Hospital (2014-2019), reports its evolution over a previous period (2008-2013), and analyses the nontypeable H. influenzae (NTHi) population structure using a clade-related classification.Clinical data, antimicrobial susceptibility and serotyping (2014-2019, n = 72) were studied and compared with the previous period data (2008-2013, n = 82). Population structure was assessed by MLST, SNP-based phylogenetic analysis and clade-related classification.The incidence of invasive H. influenzae disease remained constant (average 2.13 cases per 100,000 population), while the 30-day mortality rate decreased (20.7% to 13.9%, respectively). Immunosuppressive therapy (39%) and malignancy (35.1%) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates increased slightly (8.5-16.7%, 0-4.2%, respectively). NTHi were the main cause of invasive disease in both periods (84.3%, 86.1%), followed by serotype f (12.9%, 8.3%). NTHi displayed high genetic diversity. However, a cluster of 28 STs (n = 47), associated with clade V, included NTHi strains of the most prevalent STs (ST3, ST14, ST103 and ST139), many of which increased their frequency over time. ST103 and ST160 were associated with an increase in ß-lactam resistance.Invasive H. influenzae disease is uncommon, but severe, especially in elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing ß-lactam resistance over time.