# Antimicrobial Resistance and Mortality in Carbapenem-Resistant Pseudomonas aeruginosa Infections in Southern Thailand

## TL;DR

This study in Southern Thailand found high mortality from carbapenem-resistant Pseudomonas aeruginosa infections and identified key resistance mechanisms and risk factors.

## Contribution

The study provides new insights into resistance mechanisms and clinical outcomes of CRPA in Southern Thailand, highlighting regional differences in MBL prevalence.

## Key findings

- MexAB-OprM efflux pump overexpression was the most common resistance mechanism in CRPA isolates.
- 30-day mortality was 30.5%, with sepsis and comorbidities as significant risk factors.
- Colistin and amikacin remained effective against CRPA despite high β-lactam MICs.

## Abstract

Background/Objectives: Carbapenem-resistant Pseudomonas aeruginosa (CRPA) is an important pathogen associated with high mortality and treatment failure rates. We aimed to assess the susceptibility of CRPA to antipseudomonal agents, identify its resistance mechanisms, and evaluate clinical outcomes in a sample of CRPA isolates. Methods: This was an in vitro study of a clinical isolate of CRPA from hospitalized patients with CRPA infection and a retrospective observational study of these patients, who were diagnosed between 14 February 2021 and 10 August 2023 at Songklanagarind Hospital in Songkhla, Thailand. In vitro experiments were conducted to determine the minimum inhibitory concentrations (MICs) of the antipseudomonal agents using the broth microdilution method. Resistance mechanisms were assessed using the modified carbapenem inactivation method, combined disk tests, and quantitative real-time reverse transcription polymerase chain reaction. Results: A total of 140 CRPA isolates were analyzed. Both traditional and novel β-lactams had high MICs. The most common resistance mechanism was the upregulation of the MexAB-OprM efflux pump (81.3%), followed by the downregulation of the OprD porin (48.9%) and metallo-β-lactamase (MBL) production (45.0%), and the overexpression of blaAmpC (41.0%). The 30-day all-cause mortality rate was 30.5%. The risk factors associated with 30-day mortality included a Charlson Comorbidity Index of ≥5 (OR: 3.43; 95% CI: 1.07–10.99; p = 0.03), sepsis (OR: 10.62; 95% CI: 1.26–89.44; p = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67–11.55; p < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04–0.74; p = 0.01). Conclusions: This study revealed higher MIC values of all β-lactams for CRPA, while colistin and amikacin remained effective. The resistance mechanisms included MexAB-OprM overexpression, OprD downregulation, MBL production, and blaAmpC overexpression, with a higher prevalence of MBL than in other regions of Thailand. High 30-day mortality was associated with comorbidities, sepsis, and septic shock, but active therapy reduced mortality.