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Detection of blaCTX-M-15 in an integrative and conjugative element in four extensively drug-resistant Haemophilus
L Saiz-Escobedo1, I Cadenas-Jiménez2, R Olmos1
1Microbiology Department, Hospital Universitari de Bellvitge, IDIBELL-UB, Barcelona, Spain.
Abstract:
Haemophilus parainfluenzae is a commensal organism with rising numbers of multidrug-resistant (MDR) strains. This pathogen is of increasing clinical relevance in urogenital infection. The aim of this work was to identify and characterise the molecular mechanisms of resistance associated with four cephalosporin-resistant H. parainfluenzae strains collected from patients with urethritis. Antimicrobial resistance was determined by microdilution following European Committee on Antimicrobial Susceptibility Testing criteria. Strains were then analysed by whole-genome sequencing to determine clonal relationship and the molecular basis of antimicrobial resistance. Finally, a phylogenetic analysis was performed on all urogenital MDR strains of H. parainfluenzae previously isolated in our hospital. All strains were resistant to β-lactams, macrolides, tetracycline, fluoroquinolones, chloramphenicol, cotrimoxazole, and aminoglycosides. The resistance profile was compatible with the presence of an extended-spectrum β-lactamase (ESBL). Whole-genome sequencing detected blaCTX-M-15 that conferred high minimum inhibitory concentrations to cephalosporins in two novel integrative and conjugative elements (ICEHpaHUB6 and ICEHpaHUB7) that also harboured a blaTEM-1 β-lactamase. This study shows a novel blaCTX-M-15 ESBL carried in an integrative conjugative element in four extensively drug-resistant H. parainfluenzae strains. This resistance determinant could be transmitted to other sexually transmitted pathogens and this is a cause for concern.
Insights
Multidrug-resistant Haemophilus parainfluenzae strains causing urethritis harbor the blaCTX-M-15 gene. This extended-spectrum beta-lactamase, carried on novel mobile genetic elements, confers resistance to cephalosporins and raises public health concerns.
Area of Science:
- Microbiology
- Genetics
- Infectious Diseases
Background:
- Haemophilus parainfluenzae is a commensal bacterium increasingly associated with multidrug-resistant (MDR) strains.
- Urogenital infections caused by H. parainfluenzae are of growing clinical significance.
- The emergence of cephalosporin resistance in this pathogen necessitates understanding its molecular basis.
Purpose of the Study:
- To identify and characterize the molecular mechanisms of cephalosporin resistance in H. parainfluenzae.
- To investigate the genetic elements responsible for antimicrobial resistance.
- To perform phylogenetic analysis of urogenital MDR H. parainfluenzae strains.
Main Methods:
- Antimicrobial resistance profiling using European Committee on Antimicrobial Susceptibility Testing (EUCAST) criteria.
- Whole-genome sequencing for clonal analysis and identification of resistance genes.
- Phylogenetic analysis of previously isolated urogenital MDR H. parainfluenzae strains.
Main Results:
- Four H. parainfluenzae strains exhibited resistance to multiple drug classes, including beta-lactams, macrolides, tetracyclines, fluoroquinolones, chloramphenicol, cotrimoxazole, and aminoglycosides.
- Whole-genome sequencing identified the blaCTX-M-15 gene, encoding an extended-spectrum beta-lactamase (ESBL), in two novel integrative and conjugative elements (ICEHpaHUB6 and ICEHpaHUB7).
- These elements also contained the blaTEM-1 beta-lactamase gene, contributing to high cephalosporin resistance.
Conclusions:
- This study reveals a novel blaCTX-M-15 ESBL harbored within an integrative conjugative element in extensively drug-resistant H. parainfluenzae.
- The mobile nature of this resistance determinant raises concerns about its potential transmission to other sexually transmitted pathogens.
- Understanding these resistance mechanisms is crucial for managing urogenital infections and preventing further spread of antimicrobial resistance.
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