Epidemiology and population structure of Haemophilus influenzae causing invasive disease

Abstract

This study provides an update on invasive <i>Haemophilus influenzae</i> disease in Bellvitge University Hospital (2014-2019), reporting its evolution from a previous period (2008-2013) and analysing the non-typeable <i>H. influenzae</i> (NTHi) population structure using a clade-related classification. Clinical data, antimicrobial susceptibility and serotyping were studied and compared with those of the previous period. Population structure was assessed by multilocus sequence typing (MLST), SNP-based phylogenetic analysis and clade-related classification. The incidence of invasive <i>H. influenzae</i> disease remained constant between the two periods (average 2.07 cases per 100 000 population), while the 30 day mortality rate decreased (20.7-14.7 %, respectively). Immunosuppressive therapy (40 %) and malignancy (36 %) were the most frequent comorbidities. Ampicillin and fluoroquinolone resistance rates had increased between the two periods (10-17.6 % and 0-4.4 %, respectively). NTHi was the main cause of invasive disease in both periods (84.3 and 85.3 %), followed by serotype f (12.9 and 8.8 %). NTHi displayed high genetic diversity. However, two clusters of 13 (<i>n</i>=20) and 5 sequence types (STs) (<i>n</i>=10) associated with clade V included NTHi strains of the most prevalent STs (ST3 and ST103), many of which showed increased frequency over time. Moreover, ST103 and ST160 from clade V were associated with β-lactam resistance. Invasive <i>H. influenzae</i> disease is uncommon, but can be severe, especially in the elderly with comorbidities. NTHi remains the main cause of invasive disease, with ST103 and ST160 (clade V) responsible for increasing β-lactam resistance over time.