Molecular characterization of extensively drug-resistant hypervirulent Pseudomonas aeruginosa isolates in China
Jun Li1,2, Mengli Tang1, Zhaojun Liu1
1Department of Clinical Laboratory, Xiangya Hospital, Central South University, Changsha, Hunan, 410008, China.
Background:
Recently, extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) isolates have been increasingly detected and posed great challenges to clinical anti-infection treatments. However, little is known about extensively resistant hypervirulent P. aeruginosa (XDR-hvPA). In this study, we investigate its epidemiological characteristics and provide important basis for preventing its dissemination.
Methods:
Clinical XDR-PA isolates were collected from January 2018 to January 2023 and identified using matrix-assisted laser desorption/ionization-time-of-flight mass spectrometry; antibiotic susceptibility testing was performed by broth microdilution method, and minimum inhibitory concentrations (MICs) were evaluated. Virulence was evaluated using the Galleria mellonella infection model; molecular characteristics, including resistance genes, virulence genes, and homology, were determined using whole-genome sequencing.
Results:
A total of 77 XDR-PA strains were collected; 47/77 strains were XDR-hvPA. Patients aged > 60 years showed a significantly higher detection rate of XDR-hvPA than of XDR-non-hvPA. Among the 47 XDR-hvPA strains, 24 strains carried a carbapenemase gene, including blaGES-1 (10/47), blaVIM-2 (6/47), blaGES-14 (4/47), blaIMP-45 (2/47), blaKPC-2 (1/47), and blaNDM-14 (1/47). ExoU, exoT, exoY, and exoS, important virulence factors of PA, were found in 31/47, 47/47, 46/47, and 29/47 strains, respectively. Notably, two XDR-hvPA simultaneously co-carried exoU and exoS. Six serotypes (O1, O4-O7, and O11) were detected; O11 (19/47), O7 (13/47), and O4 (9/47) were the most prevalent. In 2018-2020, O4 and O7 were the most prevalent serotypes; 2021 onward, O11 (16/26) was the most prevalent serotype. Fourteen types of ST were detected, mainly ST235 (14/47), ST1158 (13/47), and ST1800 (7/47). Five global epidemic ST235 XDR-hvPA carried blaGES and showed the MIC value of ceftazidime/avibactam reached the susceptibility breakpoint (8/4 mg/L).
Conclusions:
The clinical detection rate of XDR-hvPA is unexpectedly high, particularly in patients aged > 60 years, who are seemingly more susceptible to contracting this infection. Clonal transmission of XDR-hvPA carrying blaGES, which belongs to the global epidemic ST235, was noted. Therefore, the monitoring of XDR-hvPA should be strengthened, particularly for elderly hospitalized patients, to prevent its spread.
Insights
Extensively drug-resistant hypervirulent Pseudomonas aeruginosa (XDR-hvPA) is surprisingly common, especially in older adults. This study highlights the need for increased surveillance of XDR-hvPA in elderly patients to prevent its spread.
Area of Science:
- Clinical microbiology and infectious diseases
- Genomics and molecular epidemiology
- Antimicrobial resistance
Background:
- Extensively drug-resistant Pseudomonas aeruginosa (XDR-PA) presents significant clinical challenges.
- Limited data exists on extensively drug-resistant hypervirulent P. aeruginosa (XDR-hvPA), necessitating further investigation into its characteristics and spread.
Purpose of the Study:
- To investigate the epidemiological characteristics of XDR-hvPA.
- To provide a basis for preventing the dissemination of XDR-hvPA.
Main Methods:
- Collection and identification of clinical XDR-PA isolates (2018-2023) using MALDI-TOF MS.
- Antibiotic susceptibility testing via broth microdilution to determine MICs.
- Virulence assessment using the Galleria mellonella model and whole-genome sequencing for molecular characterization (resistance/virulence genes, homology).
Main Results:
- 47 out of 77 XDR-PA strains were identified as XDR-hvPA, with a higher detection rate in patients over 60.
- Carbapenemase genes (e.g., blaGES-1, blaVIM-2) and key virulence factors (exoU, exoT, exoY, exoS) were prevalent in XDR-hvPA strains.
- Serotypes O11, O7, and O4, and sequence types ST235, ST1158, and ST1800 were the most common; ST235 XDR-hvPA strains carrying blaGES showed susceptibility to ceftazidime/avibactam.
Conclusions:
- XDR-hvPA is detected at a high rate, particularly in elderly patients (>60 years).
- Clonal transmission of XDR-hvPA, specifically ST235 strains carrying blaGES, was observed.
- Enhanced monitoring of XDR-hvPA in hospitalized elderly patients is crucial to curb its spread.
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