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, 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.