P-1294. Epidemiology of Carbapenem-resistance Mechanisms and the Utility of Newly Introduced Beta-lactams/beta-lactam Inhibitors in Patients with Pseudomonas aeruginosa Bacteremia

TL;DR

This study examines the resistance patterns of Pseudomonas aeruginosa to various new antibiotics in South Korea and finds that aztreonam-avibactam is most effective.

Contribution

The study provides new insights into the molecular mechanisms and antibiotic susceptibility patterns of CRPA in South Korea.

Findings

CRPA isolates showed the highest susceptibility to aztreonam-avibactam (90.2%) compared to other beta-lactam combinations.

The most common carbapenemase gene was blaNDM, found in 82.6% of isolates producing carbapenemase.

Porin loss was confirmed in 80.4% of isolates, contributing to resistance mechanisms.

Abstract

The aim of this study was to analyze the molecular epidemiology of carbapenem-resistance in blood isolates of carbapenem-resistant Pseudomonas aeruginosa (CRPA) and the cross-resistance to new beta-lactams/beta-lactam inhibitors.

In a prospective observational study, CRPA isolates were collected from patients diagnosed with CRPA bacteremia in a university-affiliated hospital of the Republic of Korea (ROK) from May 2020 to February 2025. CRPA isolates were tested for antibiotic susceptibility to ceftolozane-tazobactam (C/T), ceftazidime-avibactam (CZA), imipenem-relebactam (I/R), meropenem-vaborbactam (MVB), and aztreonam-avibactam (AZA) using the broth microdilution method. Molecular mechanisms of carbapenem-resistance were determined by polymerase chain reaction (PCR) for six resistance genes (blaVIM, blaIMP, blaNDM, blaGES, blaKPC, and blaOXA-48). Real-time reverse transcription PCR analysis was performed to confirm reduced expression of oprD or overexpression of mexB, mexD, mexF, mexY, and ampC.

A total of 51 patients with CRPA bacteremia were included in our analysis. In-hospital mortality rate was 52.9%. The MIC50/MIC90 of the CRPA isolates of C/T, CZA, I/R, MVB, and AZA were 4/ >256 mg/L, 16/ >256 mg/L, 8/ >256 mg/L, 32/ >256 mg/L, and 8/16 mg/L, respectively. AZA showed the highest susceptibility (90.20%), followed by C/T (50.98%), CZA (41.18%), I/R (23.53%), and MVB (19.61%). The proportion of isolates producing carbapenememase was 45.1%. Among them, blaNDM was the most common at 82.6%, followed by blaIMP (26.1%) and blaGES (17.4%). Among all isolates, porin loss and efflux pump overexpression were confirmed in 80.4% and 27.5%, respectively. Isolates non-susceptible to C/T showed 4.0% and 92.0% susceptibility to CZA and AZA, respectively, and resistance to both I/R and MVB. On the other hand, isolates non-susceptible to CZA showed 20.0% and 93.3% susceptibility to C/T and AZA, respectively, and resistance to both I/R and MVB.

In the ROK, CRPA isolates showed high resistance rates to C/T and CZA at 45.1% and 58.8%, respectively. Meanwhile, they showed the highest susceptibility at 90.2% to AZA. Therefore, the introduction of new antibiotics such as AZA is required to overcome the carbapenem-resistance of CRPA isolates in the ROK.

All Authors: No reported disclosures