Epidemiology and population structure of Haemophilus influenzae causing invasive disease

Abstract

This study provides an update on invasive Haemophilus influenzae disease in Bellvitge University Hospital (2014–2019), reporting its evolution from a previous period (2008–2013) and analysing the non-typeable H. influenzae (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 H. influenzae 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 (n=20) and 5 sequence types (STs) (n=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 H. influenzae 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.

Genetic Adaptation and Acquisition of Macrolide Resistance in Haemophilus spp. during Persistent Respiratory Tract Colonization in Chronic Obstructive Pulmonary Disease (COPD) Patients Receiving Long-Term Azithromycin Treatment

“…Phylogenetic analysis was conducted using Snippy ( github.com/tseemann/snippy ) and RAxML-NG ( github.com/amkozlov/raxml-ng ) ( 45 ), as previously described ( 46 ). H. influenzae Hi375 (GenBank accession CP009610 ) and H. parainfluenzae T3T1 (GenBank accession NC_015964 ) genomes were used as references.…”

Decalogue for the selection of oral antibiotics for lower respiratory tract infections

“…Beta-lactamase-producing strains with altered PBPs and combined resistance to amoxicillin, amoxicillin-clavulanic acid, oral cephalosporins and, to a lesser extent, third-generation cephalosporins, including cefditoren, are also increasing. As in S. pneumoniae, resistance to fluoroquinolones would be scarce and would be present mainly in patients with chronic bronchial infection and extensive exposure to this group of antimicrobials [41][42][43].…”

“…Table 1 shows the common susceptibility phenotypes in S. pneumoniae and H. influenzae, the associated resistance mechanism and the inferred prevalence of these phenotypes in Spain [36][37][38][39][40][41][42][43].…”

“…Although there are few recent data in Spanish studies, resistance in H. influenzae due to production of beta-lactamases and conferring resistance to amoxicillin, but with sensitivity to amoxicillin-clavulanic acid, has stabilised at around 20-25%. On the other hand, and as in other countries, resistance to amoxicillin and oral cephalosporins such as cefaclor or cefuroxime, and sometimes to amoxicillin-clavulanic acid, is increasing [ 40 , 41 ]. Third-generation cephalosporins, cefotaxime or ceftriaxone, would not be affected, as would cefditoren, which maintains its activity in these isolates [ 38 ].…”

Haemophilus influenzae Carriage among Healthy Children in Portugal, 2015–2019

“…Upon implementation of this vaccine, the epidemiology of invasive H. influenzae disease changed dramatically with a pronounced decline in Hib incidence [ 17 , 18 , 19 , 20 , 21 , 22 , 23 , 24 ]. Nowadays, with the widespread use of Hib vaccine, NTHi has become the main cause of H. influenzae invasive disease [ 25 , 26 , 27 , 28 , 29 ]. In addition, some non-b serotypes—Hie and Hif, in particular—have also been increasingly identified in invasive disease [ 18 , 19 , 20 ].…”