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Haemophilus influenzae one day in Denmark: prevalence, circulating clones, and dismal resistance to aminopenicillins

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Abstract

Haemophilus influenzae is a common cause of mucosal infections that warrants accurate surveillance. We aimed to assess the prevalence of the species in clinical specimens, and characterise population structure and resistance to aminopenicillins by whole genome sequencing.We assessed the point prevalence by entering the database records of 1 day in Denmark and examined the genome sequences of nationwide, collected isolates from the same day. The prevalence of H. influenzae in clinical samples on the 10th of January 2018 was 1.78 per 100,000 person-days (all samples), and 2.47 per 1000 hospital bed-days (hospital samples). Of 2009 bacteria deemed clinically relevant and collected in a concerted action by the Danish departments of clinical microbiology, 62 (3.1%) were H. influenzae. All 62 isolates belonged to phylogenetic group I and were unencapsulated. Three strains from separate Danish regions had identical core genome sequences, but a small number of intergenic mutations testified to circulating clones, rather than individual cases of patient-to-patient transmission. The TEM-1 β-lactamase gene was present in 24 strains, while 13 strains were genetically categorised as ampicillin-resistant due to substitutions in penicillin-binding protein 3; shared patterns of amino acid substitutions in unrelated strains indicated putative lateral transfer of chromosomal resistance. Circulating clones of H. influenzae are frequent, and host factors, rather than direct transmission of epidemic strains, may be the primary cause of infection. The bleak presence of ampicillin resistance revealed by sequencing of point prevalence strains underscores the necessity for close examination of testing methods.

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Data availability

Accession numbers are given in the “Materials and methods” section. The dataset analysed as part of the current study is available from the corresponding author on reasonable request.

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Acknowledgements

Members of the ODiD Consortium are as follows: Ana Rita Rebelo, Valeria Bortolaia, Pimlapas Leekitcharoenphon, and Frank Møller Aarestrup (Technical University of Denmark); Hans Linde Nielsen (DCM Aalborg); Svend Ellermann-Eriksen (DCM Aarhus); Turid Snekloth Søndergaard (DCM Sønderborg); John Eugenio Coia (DCM Esbjerg); Claus Østergaard (DCM Vejle); Michael Kemp (University of Southern Denmark); Bent Løwe Røder (DCM Slagelse); Niels Frimodt-Møller (DCM Rigshospitalet); Dennis Schrøder Hansen (DCM Herlev); Henrik Westh (DCM Hvidovre).

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Authors and Affiliations

  1. Department of Clinical Microbiology, Odense University Hospital, Odense, Denmark

    Niels Nørskov-Lauritsen

  2. Department of Clinical Microbiology, Aarhus University Hospital, Aarhus, Denmark

    Nanna Pedersen & Carl M. Kobel

  3. Data Integration and Analysis, State Serum Institute, Copenhagen, Denmark

    Janni U. H. Lam

  4. Department of Clinical Microbiology, Aalborg University Hospital, Aalborg, Denmark

    Hans L. Nielsen

  5. Department of Clinical Microbiology, Copenhagen University Hospital Herlev, Copenhagen, Denmark

    Dennis S. Hansen

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  1. Niels Nørskov-Lauritsen
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The study was conceived and planned by NNL. JL retrieved data from MiBa, and CMK performed the major part of the bioinformatics analysis. NNL analysed data and wrote the first draft of the manuscript, which was revised critically for clinical content by NP, HLN, and DSH. All authors approved the final version of the manuscript.

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Correspondence to Niels Nørskov-Lauritsen.

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Ethical approval and informed consent

Not applicable to the present study. Reported culture of H. influenzae and collected bacterial strains are linked to specimen type and a regional DCM. Information cannot be linked to patient records or original sample number, and according to Danish law, approval from science ethics committees is not required.

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The authors declare no competing interests.

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Nørskov-Lauritsen, N., Pedersen, N., Lam, J.U.H. et al. Haemophilus influenzae one day in Denmark: prevalence, circulating clones, and dismal resistance to aminopenicillins. Eur J Clin Microbiol Infect Dis 40, 2077–2085 (2021). https://doi.org/10.1007/s10096-021-04247-w

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