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Abstract

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

Funding
This study was supported by the:
  • instituto de salud carlos iii (Award CP19/00096)
    • Principle Award Recipient: SaraMartí
  • ministerio de ciencia, innovación y universidades (Award FPU16/02202)
    • Principle Award Recipient: AnnaCarrera-Salinas
  • amazon web services
    • Principle Award Recipient: SaraMartí
  • centro de investigación biomédica en red de enfermedades respiratorias (es) (Award CB06/06/0037)
    • Principle Award Recipient: CarmenArdanuy
  • instituto de salud carlos iii (Award PI16/00977)
    • Principle Award Recipient: SaraMartí
  • This is an open-access article distributed under the terms of the Creative Commons Attribution License.
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2021-12-13
2024-11-07
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References

  1. LaCross NC, Marrs CF, Gilsdorf JR. Population structure in nontypeable Haemophilus influenzae. Infect Genet Evol 2013; 14:125–136 [View Article] [PubMed]
    [Google Scholar]
  2. Slack MPE. A review of the role of Haemophilus influenzae in community-acquired pneumonia. Pneumonia (Nathan) 2015; 6:26–43 [View Article] [PubMed]
    [Google Scholar]
  3. Nørskov-Lauritsen N. Classification, identification, and clinical significance of Haemophilus and Aggregatibacter species with host specificity for humans. Clin Microbiol Rev 2014; 27:214–240 [View Article] [PubMed]
    [Google Scholar]
  4. Agrawal A, Murphy TF. Haemophilus influenzae infections in the H. influenzae type b conjugate vaccine era. J Clin Microbiol 2011; 49:3728–3732 [View Article] [PubMed]
    [Google Scholar]
  5. Sethi S, Murphy TF. Infection in the pathogenesis and course of chronic obstructive pulmonary disease. N Engl J Med 2008; 359:2355–2365 [View Article] [PubMed]
    [Google Scholar]
  6. Cardines R, Giufrè M, Pompilio A, Fiscarelli E, Ricciotti G et al. Haemophilus influenzae in children with cystic fibrosis: Antimicrobial susceptibility, molecular epidemiology, distribution of adhesins and biofilm formation. Int J Med Microbiol 2012; 302:45–52 [View Article] [PubMed]
    [Google Scholar]
  7. van de Beek D, Brouwer M, Hasbun R, Koedel U, Whitney CG et al. Community-acquired bacterial meningitis. Nat Rev Dis Primers 2016; 2:16074 [View Article] [PubMed]
    [Google Scholar]
  8. Wang S, Tafalla M, Hanssens L, Dolhain J. A review of Haemophilus influenzae disease in Europe from 2000-2014: challenges, successes and the contribution of hexavalent combination vaccines. Expert Rev Vaccines 2017; 16:1095–1105 [View Article] [PubMed]
    [Google Scholar]
  9. Heliodoro CIM, Bettencourt CR, Bajanca-Lavado MP. Portuguese Group for the Study of Haemophilus influenzae invasive infection Molecular epidemiology of invasive Haemophilus influenzae disease in Portugal: an update of the post-vaccine period, 2011-2018. Eur J Clin Microbiol Infect Dis 2020; 39:1471–1480 [View Article] [PubMed]
    [Google Scholar]
  10. Wen S, Feng D, Chen D, Yang L, Xu Z. Molecular epidemiology and evolution of Haemophilus influenzae. Infect Genet Evol 2020; 80:104205 [View Article] [PubMed]
    [Google Scholar]
  11. Robinson DA, Thomas JC, Hanage WP. Population structure of pathogenic bacteria. In Genetics and Evolution of Infectious Diseases Elsevier Inc; 2011 pp 43–57
    [Google Scholar]
  12. De Chiara M, Hood D, Muzzi A, Pickard DJ, Perkins T et al. Genome sequencing of disease and carriage isolates of nontypeable Haemophilus influenzae identifies discrete population structure. Proc Natl Acad Sci U S A 2014; 111:5439–5444 [View Article] [PubMed]
    [Google Scholar]
  13. Staples M, Graham RMA, Jennison AV. Characterisation of invasive clinical Haemophilus influenzae isolates in Queensland, Australia using whole-genome sequencing. Epidemiol Infect 2017; 145:1727–1736 [View Article] [PubMed]
    [Google Scholar]
  14. Pinto M, González-Díaz A, Machado MP, Duarte S, Vieira L et al. Insights into the population structure and pan-genome of Haemophilus influenzae. Infect Genet Evol 2019; 67:126–135 [View Article] [PubMed]
    [Google Scholar]
  15. Puig C, Grau I, Marti S, Tubau F, Calatayud L et al. Clinical and molecular epidemiology of Haemophilus influenzae causing invasive disease in adult patients. PLoS One 2014; 9:e112711 [View Article] [PubMed]
    [Google Scholar]
  16. Clinical Laboratory Standards Institute Performance standards for antimicrobial susceptibility testing: 29th Edition. In CLSI Supplement Document M100 Wayne, PA: 2019
    [Google Scholar]
  17. Francisco AP, Vaz C, Monteiro PT, Melo-Cristino J, Ramirez M et al. PHYLOViZ: Phylogenetic inference and data visualization for sequence based typing methods. BMC Bioinformatics 2012; 13:87 [View Article] [PubMed]
    [Google Scholar]
  18. Watts SC, Holt KE. HICAP: In silico serotyping of the Haemophilus influenzae capsule locus. J Clin Microbiol 2019; 57:e00190-19 [View Article] [PubMed]
    [Google Scholar]
  19. Bortolaia V, Kaas RS, Ruppe E, Roberts MC, Schwarz S et al. ResFinder 4.0 for predictions of phenotypes from genotypes. J Antimicrob Chemother 2020; 75:3491–3500 [View Article] [PubMed]
    [Google Scholar]
  20. Kozlov AM, Darriba D, Flouri T, Morel B, Stamatakis A. RAxML-NG: a fast, scalable and user-friendly tool for maximum likelihood phylogenetic inference. Bioinformatics 2019; 35:4453–4455 [View Article] [PubMed]
    [Google Scholar]
  21. Pattengale ND, Alipour M, Bininda-Emonds ORP, Moret BME, Stamatakis A. How many bootstrap replicates are necessary?. J Comput Biol 2010; 17:337–354 [View Article] [PubMed]
    [Google Scholar]
  22. Croucher NJ, Page AJ, Connor TR, Delaney AJ, Keane JA et al. Rapid phylogenetic analysis of large samples of recombinant bacterial whole genome sequences using Gubbins. Nucleic Acids Res 2015; 43:e15. [View Article] [PubMed]
    [Google Scholar]
  23. Treangen TJ, Ondov BD, Koren S, Phillippy AM. The Harvest suite for rapid core-genome alignment and visualization of thousands of intraspecific microbial genomes. Genome Biol 2014; 15:524. [View Article] [PubMed]
    [Google Scholar]
  24. Yu G, Smith DK, Zhu H, Guan Y, Lam TT et al. ggtree : an r package for visualization and annotation of phylogenetic trees with their covariates and other associated data. Methods Ecol Evol 2016; 8:28–36 [View Article]
    [Google Scholar]
  25. Dabernat H, Delmas C, Seguy M, Pelissier R, Faucon G et al. Diversity of beta-lactam resistance-conferring amino acid substitutions in penicillin-binding protein 3 of Haemophilus influenzae. Antimicrob Agents Chemother 2002; 46:2208–2218 [View Article] [PubMed]
    [Google Scholar]
  26. Tacconelli E, Carrara E, Savoldi A, Harbarth S, Mendelson M et al. Discovery, research, and development of new antibiotics: the WHO priority list of antibiotic-resistant bacteria and tuberculosis. Lancet Infect Dis 2018; 18:318–327 [View Article] [PubMed]
    [Google Scholar]
  27. Whittaker R, Economopoulou A, Dias JG, Bancroft E, Ramliden M et al. Epidemiology of Invasive Haemophilus influenzae Disease, Europe, 2007-2014. Emerg Infect Dis 2017; 23:396–404 [View Article] [PubMed]
    [Google Scholar]
  28. Soeters HM, Blain A, Pondo T, Doman B, Farley MM et al. Current epidemiology and trends in invasive Haemophilus influenzae Disease-United States, 2009-2015. Clin Infect Dis 2018; 67:881–889 [View Article] [PubMed]
    [Google Scholar]
  29. GBD Chronic Respiratory Disease Collaborators Prevalence and attributable health burden of chronic respiratory diseases, 1990-2017: a systematic analysis for the Global Burden of Disease Study 2017. Lancet Respir Med 2020; 8:585–596 [View Article] [PubMed]
    [Google Scholar]
  30. Haro JM, Tyrovolas S, Garin N, Diaz-Torne C, Carmona L et al. The burden of disease in Spain: results from the global burden of disease study 2010. BMC Med 2014; 12:236. [View Article] [PubMed]
    [Google Scholar]
  31. Fujii M, Gomi H, Ishioka H, Takamura N. Bacteremic renal stone-associated urinary tract infection caused by nontypable Haemophilus influenzae: A rare invasive disease in an immunocompetent patient. IDCases 2017; 7:11–13 [View Article] [PubMed]
    [Google Scholar]
  32. Stærk M, Tolouee SA, Christensen JJ. Nontypable Haemophilus influenzae septicemia and urinary tract infection associated with renal stone disease. Open Microbiol J 2018; 12:243–247 [View Article] [PubMed]
    [Google Scholar]
  33. Martin D, Dbouk RH, Deleon-Carnes M, del Rio C, Guarner J. Haemophilus influenzae acute endometritis with bacteremia: Case report and literature review. Diagn Microbiol Infect Dis 2013; 76:235–236 [View Article] [PubMed]
    [Google Scholar]
  34. Langereis JD, de Jonge MI. Invasive disease caused by nontypeable Haemophilus influenzae. Emerg Infect Dis 2015; 21:1711–1718 [View Article] [PubMed]
    [Google Scholar]
  35. Chiappini E, Inturrisi F, Orlandini E, de Martino M, de Waure C. Hospitalization rates and outcome of invasive bacterial vaccine-preventable diseases in Tuscany: A historical cohort study of the 2000-2016 period. BMC Infect Dis 2018; 18:396 [View Article] [PubMed]
    [Google Scholar]
  36. Blain A, MacNeil J, Wang X, Bennett N, Farley MM et al. Invasive Haemophilus influenzae Disease in Adults ≥65 Years, United States, 2011. Open Forum Infect Dis 2014; 1:fu044 [View Article] [PubMed]
    [Google Scholar]
  37. Tsang RSW, Shuel M, Whyte K, Hoang L, Tyrrell G et al. Antibiotic susceptibility and molecular analysis of invasive Haemophilus influenzae in Canada, 2007 to 2014. J Antimicrob Chemother 2017; 72:1314–1319 [View Article] [PubMed]
    [Google Scholar]
  38. Giufrè M, Fabiani M, Cardines R, Riccardo F, Caporali MG et al. Increasing trend in invasive non-typeable Haemophilus influenzae disease and molecular characterization of the isolates, Italy, 2012-2016. Vaccine 2018; 36:6615–6622 [View Article] [PubMed]
    [Google Scholar]
  39. European Centre for Disease Prevention and Control (ECDC) Haemophilus influenzae annual epidemiological report for 2018 Stockholm: 2020
    [Google Scholar]
  40. Ulanova M, Tsang RSW. Haemophilus influenzae serotype a as a cause of serious invasive infections. Lancet Infect Dis 2014; 14:70–82 [View Article] [PubMed]
    [Google Scholar]
  41. San Millan A, Garcia-Cobos S, Escudero JA, Hidalgo L, Gutierrez B et al. Haemophilus influenzae clinical isolates with plasmid pB1000 bearing blaROB-1: Fitness cost and interspecies dissemination. Antimicrob Agents Chemother 2010; 54:1506–1511 [View Article] [PubMed]
    [Google Scholar]
  42. Shoji H, Shirakura T, Fukuchi K, Takuma T, Hanaki H et al. A molecular analysis of quinolone-resistant Haemophilus influenzae: Validation of the mutations in quinolone resistance-determining regions. J Infect Chemother 2014; 20:250–255 [View Article] [PubMed]
    [Google Scholar]
  43. Puig C, Tirado-Vélez JM, Calatayud L, Tubau F, Garmendia J et al. Molecular characterization of fluoroquinolone resistance in nontypeable Haemophilus influenzae clinical isolates. Antimicrob Agents Chemother 2015; 59:461–466 [View Article] [PubMed]
    [Google Scholar]
  44. Vos M, Didelot X. A comparison of homologous recombination rates in bacteria and archaea. ISME J 2009; 3:199–208 [View Article] [PubMed]
    [Google Scholar]
  45. Pettigrew MM, Ahearn CP, Gent JF, Kong Y, Gallo MC et al. Haemophilus influenzae genome evolution during persistence in the human airways in chronic obstructive pulmonary disease. Proc Natl Acad Sci U S A 2018; 115:E3256–E3265 [View Article] [PubMed]
    [Google Scholar]
  46. Kc R, Leong KWC, Harkness NM, Lachowicz J, Gautam SS et al. Whole-genome analyses reveal gene content differences between nontypeable Haemophilus influenzae isolates from chronic obstructive pulmonary disease compared to other clinical phenotypes. Microbial Genomics 2020; 6:1–12 [View Article]
    [Google Scholar]
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