Whole genome sequencing of ceftolozane/tazobactam-resistant, XDR Pseudomonas aeruginosa ST773 in hospitalized critically ill infants and young children with ventilator-associated pneumonia.
Ventilator-associated pneumonia (VAP) caused by Pseudomonas aeruginosa poses a major therapeutic challenge for critically ill infants and young children.
In this study, we assessed the antimicrobial susceptibility profiles of 42 P. aeruginosa isolates recovered from neonatal and paediatric intensive care unit (NICUs and PICU) patients with VAP between March and September 2021. Five isolates (11.9%) exhibited an extensively drug-resistant (XDR) phenotype and were resistant to both ceftazidime-avibactam and ceftolozane-tazobactam. These five isolates were subjected to whole-genome sequencing (WGS) and comparative genomic analyses.
All five isolates belonged to serogroup O11 and sequence type ST773. Nevertheless, WGS-based phylogenetic analyses, such as core genome MLST and SNP-based phylogeny, showed that the isolates were non-clonal and had a closer genetic relationship to previously identified ST773 strains from Egypt and Germany. Several multidrug efflux systems and a broad range of acquired antimicrobial resistance genes, such as blaNDM-1, rmtB4, tet(G), and flor2, carried on a conserved integrative conjugative element previously reported in ST773, were found by genomic analysis. Furthermore, on a genomic island inserted downstream of the glmS gene, a class 1 integron containing qnrVC1, aadA11, qacEΔ1, and sul1 was found. All strains possessed the same quinolone resistance-determining region alterations (gyrA T83I and parC S87L) and the same array of virulence-associated genes linked to motility, secretion systems, iron acquisition, quorum sensing, and toxin production.
This study reports the identification of non-clonal, XDR P. aeruginosa ST773 isolates associated with VAP in critically ill infants and young children. Despite their non-clonal nature, the isolates shared key features, including mobile genetic elements carrying important resistance genes and a consistent virulence gene profile. These findings highlight the clinical significance of this sequence type and raise concerns about its potential impact in the NICU and PICU settings. Continuous genomic surveillance, along with improved antimicrobial stewardship and stricter infection control practices, remains essential to limit its spread.
In this study, we assessed the antimicrobial susceptibility profiles of 42 P. aeruginosa isolates recovered from neonatal and paediatric intensive care unit (NICUs and PICU) patients with VAP between March and September 2021. Five isolates (11.9%) exhibited an extensively drug-resistant (XDR) phenotype and were resistant to both ceftazidime-avibactam and ceftolozane-tazobactam. These five isolates were subjected to whole-genome sequencing (WGS) and comparative genomic analyses.
All five isolates belonged to serogroup O11 and sequence type ST773. Nevertheless, WGS-based phylogenetic analyses, such as core genome MLST and SNP-based phylogeny, showed that the isolates were non-clonal and had a closer genetic relationship to previously identified ST773 strains from Egypt and Germany. Several multidrug efflux systems and a broad range of acquired antimicrobial resistance genes, such as blaNDM-1, rmtB4, tet(G), and flor2, carried on a conserved integrative conjugative element previously reported in ST773, were found by genomic analysis. Furthermore, on a genomic island inserted downstream of the glmS gene, a class 1 integron containing qnrVC1, aadA11, qacEΔ1, and sul1 was found. All strains possessed the same quinolone resistance-determining region alterations (gyrA T83I and parC S87L) and the same array of virulence-associated genes linked to motility, secretion systems, iron acquisition, quorum sensing, and toxin production.
This study reports the identification of non-clonal, XDR P. aeruginosa ST773 isolates associated with VAP in critically ill infants and young children. Despite their non-clonal nature, the isolates shared key features, including mobile genetic elements carrying important resistance genes and a consistent virulence gene profile. These findings highlight the clinical significance of this sequence type and raise concerns about its potential impact in the NICU and PICU settings. Continuous genomic surveillance, along with improved antimicrobial stewardship and stricter infection control practices, remains essential to limit its spread.
Authors
Hamed Hamed, Hussein Hussein, Ezz El Arab Ezz El Arab, Al-Agamy Al-Agamy, Aufy Aufy, Abdelmoteleb Abdelmoteleb, Zafer Zafer
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