{
  "abstract": "Introduction: Haemophilus influenzae ( Hi ) is a commensal pathogen of the respiratory epithelium. However, it can also cause a wide range of infections, from minor ear, nose and throat conditions to severe sepsis and meningitis. In this context, aminopenicillins, either alone or in combination with a beta-lactamase inhibitor, and third-generation cephalosporins are the preferred treatment options. Antibiotic resistance surveillance is important in providing a basis for recommendations on the empirical use of antibiotic agents. Objectives: To analyse the dynamics of the susceptibility rates of invasive and non-invasive Hi isolates to aminopenicillins and third-generation cephalosporins, and to compare the molecular mechanisms of resistance. Furthermore, an analysis of the epidemiology of invasive and non-invasive infections in Germany was conducted. Methods: Non-invasive Hi isolates (n = 208) were collected from a sentinel network of diagnostic laboratories in a prospective multicentre prevalence study conducted by the Paul-Ehrlich Society in the period 10/2022–03/2023. Invasive isolates (n = 905) were collected at the NRZMHi at the same time period. Antimicrobial susceptibility testing was carried out using gradient agar diffusion (GAD) test. MICs were interpreted in accordance with EUCAST guidelines. β-lactamase production was tested using the Nitrocefin test. Sequencing of the ftsI gene, encoding penicillin binding protein 3 (PBP3) was performed to analyse the molecular mechanism of β-lactam resistance among all β-lactamase negative ampicillin resistant (BLNAR). Results: The results showed no significant differences in the proportions of β-lactamase negative ampicillin-susceptible (BLNAS, 79.3% vs. 77.5%), β-lactamase positive ampicillin-resistant (BLPAR, 13% vs. 15%) and BLNAR Hi (6.7% vs. 7.4%) in non-invasive and invasive isolates, respectively. Resistance to third-generation cephalosporins was rare in both non-invasive and invasive isolates (1.0% vs 1.3%). Most BLNAR exhibited PBP3 amino-acid substitutions of group II, most frequently IIb and IIa. Furthermore, 92% of isolates carrying group III PBP3 mutations (n = 12/13) exhibited increased MICs against cefotaxime (≥0.125 mg/l). The present study revealed that, compared to invasive encapsulated isolates (n = 104), NTHi (n = 801) exhibited a significantly higher propensity towards ampicillin resistance (p < 0.0001; Fisher's exact test). The vast majority of non-invasive isolates were also NTHi (204/208). All non-invasive ampicillin-resistant strains were NTHi (n = 42). Conclusions: The findings generally indicated that resistance rates of invasive and non-invasive isolates were comparable. The molecular analysis revealed the presence of characteristic PBP3 mutations in BLNAR and cefotaxime-resistant isolates. Overall, the resistance rates to β-lactam antibiotics do not seem to have changed in Germany.",
  "abstract_shown": true,
  "affiliations": [
    "Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Wuerzburg, Germany, Germany; Corresponding author.",
    "Antiinfective Intelligence GmbH, Cologne, Germany; Paul Ehrlich Society for Infection Therapy, Cologne, Germany",
    "Paul Ehrlich Society for Infection Therapy, Cologne, Germany",
    "Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Wuerzburg, Germany, Germany"
  ],
  "article_type": null,
  "arxiv": null,
  "author_total": 5,
  "authors": [
    {
      "affs": [
        0
      ],
      "name": "Katherina Heroth"
    },
    {
      "affs": [
        1
      ],
      "name": "Esther Wohlfarth"
    },
    {
      "affs": [
        2
      ],
      "name": "Michael Kresken"
    },
    {
      "affs": [
        3
      ],
      "name": "Heike Claus"
    },
    {
      "affs": [
        3
      ],
      "name": "Thiên-Trí Lâm"
    }
  ],
  "bibtex": "https://research.draconitic.com/paper/7sh9cskfr33gk.bib",
  "cited_by": 0,
  "doi": "10.1016/j.ijmm.2026.151749",
  "fulltext_url": "http://www.sciencedirect.com/science/article/pii/S1438422126000524",
  "id": "7sh9cskfr33gk",
  "issns": [
    "1438-4221",
    "1618-0607"
  ],
  "landing_url": "https://doi.org/10.1016/j.ijmm.2026.151749",
  "language": "en",
  "licence": "CC-BY",
  "licence_label": "CC BY",
  "licence_source": "journal",
  "licence_url": "https://creativecommons.org/licenses/by/4.0/",
  "metadata_licence": null,
  "native_subjects": [
    [
      "lcc",
      "QR1-502"
    ],
    [
      "lcc",
      "RZ201-999"
    ],
    [
      "openalex",
      "1313|Antibiotic Resistance in Bacteria"
    ]
  ],
  "openalex": "W7222804505",
  "pdf_url": null,
  "pmcid": null,
  "pmid": null,
  "published": "2026-10-30",
  "publisher": "Elsevier",
  "ris": "https://research.draconitic.com/paper/7sh9cskfr33gk.ris",
  "sources": [
    {
      "first_seen": "2026-10-30T13:44:30Z",
      "native_id": "5087d91e69ca4a7485f092f2099f04cb",
      "source": "doaj",
      "url": "https://doi.org/10.1016/j.ijmm.2026.151749"
    }
  ],
  "subjects": [
    {
      "field": "biology",
      "origin": "lcc:QR1-502",
      "subfield": "microbiology"
    }
  ],
  "title": "Beta-lactam resistance in invasive and non-invasive",
  "title_text": "Beta-lactam resistance in invasive and non-invasive",
  "type": "peer-reviewed",
  "updated_at": "2026-10-30T13:44:30Z",
  "url": "https://research.draconitic.com/paper/7sh9cskfr33gk",
  "venue": "International Journal of Medical Microbiology",
  "versions": []
}