Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism

Background: The investigation into risk factors, molecular epidemiology, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in pediatric populations in China is currently inadequate. Methods: To assess epidemiology, molecular characteristics, and resistance mechanisms, v...

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Main Authors: Lijun Yin, Lu Lu, Leiyan He, Gangfeng Yan, Guoping Lu, Xiaowen Zhai, Chuanqing Wang
Format: Article
Language:English
Published: Elsevier 2025-02-01
Series:Journal of Infection and Public Health
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Online Access:http://www.sciencedirect.com/science/article/pii/S187603412400368X
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author Lijun Yin
Lu Lu
Leiyan He
Gangfeng Yan
Guoping Lu
Xiaowen Zhai
Chuanqing Wang
author_facet Lijun Yin
Lu Lu
Leiyan He
Gangfeng Yan
Guoping Lu
Xiaowen Zhai
Chuanqing Wang
author_sort Lijun Yin
collection DOAJ
description Background: The investigation into risk factors, molecular epidemiology, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in pediatric populations in China is currently inadequate. Methods: To assess epidemiology, molecular characteristics, and resistance mechanisms, virulence-associated genes were analyzed, alongside multi locus sequence typing (MLST), PCR, and qRT-PCR. Finding: Multivariate analysis identified prolonged hospitalization (OR: 1.026; 95 % CI: 1.004–1.049; P = 0.023) and increased exposure to enzyme inhibitor complex preparations (OR: 3.165; 95 % confidence interval [CI]: 1.113–8.999; P = 0.031) as independent risk factors for CRPA healthcare-associated infections (HAIs). Mortality rates were significantly higher in the HAI group compared to the non-HAI group (19.1 % vs. 6.0 %, P = 0.021). Analysis of virulence-associated gene combinations revealed 10 and 15 distinct profiles among HAI and non-HAI isolates, respectively, characterized by exoS−/exoU+ or exoS+ /exoU− genotypes, with no isolates exhibiting both exoS+ and exoU+ genotypes concurrently.Infections predominantly correlated with CC244, with a significantly greater occurrence in the HAI group (72.1 % vs. 46.3 %, P = 0.002). Antimicrobial susceptibility testing identified that both CC244 + and HAI isolates demonstrated elevated resistance across all tested antibiotics. Furthermore, low oprD expression was observed in 77.9 % of HAI isolates and 67.2 % of non-HAI isolates, while increased ampC production and mexB gene overexpression were infrequently detected (all P > 0.05). Conclusions: Prolonged hospital stays and an increased exposure to enzyme–inhibitor complex therapies were identified as independent risk factors for CRPA HAIs. CRPA demonstrated considerable genetic diversity, with STs predominantly represented by CC244, and virulence-associated genes have spread. The primary mechanism driving carbapenem resistance involved the downregulation of outer membrane porin protein oprD, accompanied by oprD mutation inactivation.
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spelling doaj-art-7c4118e5bde5443f852f61c3b64131562025-01-21T04:12:57ZengElsevierJournal of Infection and Public Health1876-03412025-02-01182102634Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanismLijun Yin0Lu Lu1Leiyan He2Gangfeng Yan3Guoping Lu4Xiaowen Zhai5Chuanqing Wang6Department of Nosocomial Infection Control, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Nosocomial Infection Control, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Clinical Laboratory Center, the Clinical Microbiology Laboratory, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, ChinaDepartment of Pediatric Intensive Care Unit, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Corresponding authors.Department of Hematology, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Corresponding authors.Department of Nosocomial Infection Control, The Clinical Laboratory, Clinical Microbiology Laboratory, Children’s Hospital of Fudan University, National Children's Medical Center, Shanghai, China; Corresponding authors.Background: The investigation into risk factors, molecular epidemiology, and resistance mechanisms of carbapenem-resistant Pseudomonas aeruginosa (CRPA) in pediatric populations in China is currently inadequate. Methods: To assess epidemiology, molecular characteristics, and resistance mechanisms, virulence-associated genes were analyzed, alongside multi locus sequence typing (MLST), PCR, and qRT-PCR. Finding: Multivariate analysis identified prolonged hospitalization (OR: 1.026; 95 % CI: 1.004–1.049; P = 0.023) and increased exposure to enzyme inhibitor complex preparations (OR: 3.165; 95 % confidence interval [CI]: 1.113–8.999; P = 0.031) as independent risk factors for CRPA healthcare-associated infections (HAIs). Mortality rates were significantly higher in the HAI group compared to the non-HAI group (19.1 % vs. 6.0 %, P = 0.021). Analysis of virulence-associated gene combinations revealed 10 and 15 distinct profiles among HAI and non-HAI isolates, respectively, characterized by exoS−/exoU+ or exoS+ /exoU− genotypes, with no isolates exhibiting both exoS+ and exoU+ genotypes concurrently.Infections predominantly correlated with CC244, with a significantly greater occurrence in the HAI group (72.1 % vs. 46.3 %, P = 0.002). Antimicrobial susceptibility testing identified that both CC244 + and HAI isolates demonstrated elevated resistance across all tested antibiotics. Furthermore, low oprD expression was observed in 77.9 % of HAI isolates and 67.2 % of non-HAI isolates, while increased ampC production and mexB gene overexpression were infrequently detected (all P > 0.05). Conclusions: Prolonged hospital stays and an increased exposure to enzyme–inhibitor complex therapies were identified as independent risk factors for CRPA HAIs. CRPA demonstrated considerable genetic diversity, with STs predominantly represented by CC244, and virulence-associated genes have spread. The primary mechanism driving carbapenem resistance involved the downregulation of outer membrane porin protein oprD, accompanied by oprD mutation inactivation.http://www.sciencedirect.com/science/article/pii/S187603412400368XCarbapenem resistance P. aeruginosaHealthcare-associated infectionsVirulence geneoprDST244Pediatric patients
spellingShingle Lijun Yin
Lu Lu
Leiyan He
Gangfeng Yan
Guoping Lu
Xiaowen Zhai
Chuanqing Wang
Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
Journal of Infection and Public Health
Carbapenem resistance P. aeruginosa
Healthcare-associated infections
Virulence gene
oprD
ST244
Pediatric patients
title Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
title_full Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
title_fullStr Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
title_full_unstemmed Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
title_short Non-carbapenem-producing carbapenem-resistant Pseudomonas aeruginosa in children: Risk factors, molecular epidemiology, and resistance mechanism
title_sort non carbapenem producing carbapenem resistant pseudomonas aeruginosa in children risk factors molecular epidemiology and resistance mechanism
topic Carbapenem resistance P. aeruginosa
Healthcare-associated infections
Virulence gene
oprD
ST244
Pediatric patients
url http://www.sciencedirect.com/science/article/pii/S187603412400368X
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