Beta-lactam resistance in invasive and non-invasive
4 affiliations
- 1Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Wuerzburg, Germany, Germany; Corresponding author.
- 2Antiinfective Intelligence GmbH, Cologne, Germany; Paul Ehrlich Society for Infection Therapy, Cologne, Germany
- 3Paul Ehrlich Society for Infection Therapy, Cologne, Germany
- 4Institute for Hygiene and Microbiology, National Reference Centre for Meningococci and Haemophilus influenzae, University of Wuerzburg, Germany, Germany
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.
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BibTeX
@article{heroth2026betalactam,
title = {{Beta-lactam resistance in invasive and non-invasive}},
author = {Katherina Heroth and Esther Wohlfarth and Michael Kresken and Heike Claus and Thiên-Trí Lâm},
journal = {International Journal of Medical Microbiology},
year = {2026},
month = oct,
doi = {10.1016/j.ijmm.2026.151749},
url = {https://doi.org/10.1016/j.ijmm.2026.151749},
note = {CC BY},
}
RIS
TY - JOUR
TI - Beta-lactam resistance in invasive and non-invasive
AU - Katherina Heroth
AU - Esther Wohlfarth
AU - Michael Kresken
AU - Heike Claus
AU - Thiên-Trí Lâm
PY - 2026
DA - 2026/10/30
JO - International Journal of Medical Microbiology
DO - 10.1016/j.ijmm.2026.151749
UR - https://doi.org/10.1016/j.ijmm.2026.151749
AB - 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.
SN - 1438-4221
SN - 1618-0607
ER -