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

Lijun Yin; Lu Lu; Leiyan He; Gangfeng Yan; Guoping Lu; Xiaowen Zhai; Chuanqing Wang

doi:10.1016/j.jiph.2024.102634

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

J Infect Public Health. 2024 Dec 30;18(2):102634. doi: 10.1016/j.jiph.2024.102634. Online ahead of print.

Authors

Lijun Yin¹, Lu Lu¹, Leiyan He², Gangfeng Yan³, Guoping Lu⁴, Xiaowen Zhai⁵, Chuanqing Wang⁶

Affiliations

¹ Department of Nosocomial Infection Control, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
² Department of Clinical Laboratory Center, the Clinical Microbiology Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
³ Department of Pediatric Intensive Care Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China.
⁴ Department of Pediatric Intensive Care Unit, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China. Electronic address: [email protected].
⁵ Department of Hematology, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China. Electronic address: [email protected].
⁶ Department of Nosocomial Infection Control, The Clinical Laboratory, Clinical Microbiology Laboratory, Children's Hospital of Fudan University, National Children's Medical Center, Shanghai, China. Electronic address: [email protected].

PMID: 39809076
DOI: 10.1016/j.jiph.2024.102634

Abstract

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.

Keywords: Carbapenem resistance P. aeruginosa; Healthcare-associated infections; Pediatric patients; ST244; Virulence gene; oprD.