Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand

<b>Background/Objectives</b>: Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (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 mechan...

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Main Authors: Parichart Chotimakorn, Sutthiporn Pattharachayakul, Yongyut Lertsrisatit, Wichai Santimaleeworagun, Pimpimon Tansakul, Mingkwan Yingkajorn, Sureerat Chelae, Rattanaruji Pomwised, Arnon Chukamnerd, Rosesathorn Soontarach, Sarunyou Chusri
Format: Article
Language:English
Published: MDPI AG 2025-03-01
Series:Antibiotics
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Online Access:https://www.mdpi.com/2079-6382/14/3/322
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author Parichart Chotimakorn
Sutthiporn Pattharachayakul
Yongyut Lertsrisatit
Wichai Santimaleeworagun
Pimpimon Tansakul
Mingkwan Yingkajorn
Sureerat Chelae
Rattanaruji Pomwised
Arnon Chukamnerd
Rosesathorn Soontarach
Sarunyou Chusri
author_facet Parichart Chotimakorn
Sutthiporn Pattharachayakul
Yongyut Lertsrisatit
Wichai Santimaleeworagun
Pimpimon Tansakul
Mingkwan Yingkajorn
Sureerat Chelae
Rattanaruji Pomwised
Arnon Chukamnerd
Rosesathorn Soontarach
Sarunyou Chusri
author_sort Parichart Chotimakorn
collection DOAJ
description <b>Background/Objectives</b>: Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>bla</i><sub>AmpC</sub> (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; <i>p</i> = 0.03), sepsis (OR: 10.62; 95% CI: 1.26–89.44; <i>p</i> = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67–11.55; <i>p</i> < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04–0.74; <i>p</i> = 0.01). <b>Conclusions</b>: 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 <i>bla</i><sub>AmpC</sub> 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.
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spelling doaj-art-99e723822ef5453dbf8961973ca24f6c2025-08-20T02:11:17ZengMDPI AGAntibiotics2079-63822025-03-0114332210.3390/antibiotics14030322Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern ThailandParichart Chotimakorn0Sutthiporn Pattharachayakul1Yongyut Lertsrisatit2Wichai Santimaleeworagun3Pimpimon Tansakul4Mingkwan Yingkajorn5Sureerat Chelae6Rattanaruji Pomwised7Arnon Chukamnerd8Rosesathorn Soontarach9Sarunyou Chusri10College of Pharmacotherapy Thailand, Nonthaburi 11000, ThailandDepartment of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, ThailandDepartment of Clinical Pharmacy, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, ThailandDepartment of Pharmacy, Faculty of Pharmacy, Silpakorn University, Nakorn Pathom 73000, ThailandDepartment of Pharmacognosy and Pharmaceutical Botany, Faculty of Pharmaceutical Sciences, Prince of Songkla University, Songkhla 90110, ThailandDepartment of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ThailandDepartment of Pathology, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ThailandDivision of Biological Science, Faculty of Science, Prince of Songkla University, Songkhla 90110, ThailandDivision of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ThailandDivision of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, ThailandDivision of Infectious Diseases, Department of Internal Medicine, Faculty of Medicine, Prince of Songkla University, Songkhla 90110, Thailand<b>Background/Objectives</b>: Carbapenem-resistant <i>Pseudomonas aeruginosa</i> (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. <b>Methods</b>: 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. <b>Results</b>: 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 <i>bla</i><sub>AmpC</sub> (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; <i>p</i> = 0.03), sepsis (OR: 10.62; 95% CI: 1.26–89.44; <i>p</i> = 0.03), and septic shock (OR: 4.39; 95% CI: 1.67–11.55; <i>p</i> < 0.01). In contrast, receiving active documented therapy was significantly associated with reduced mortality (OR: 0.17; 95% CI: 0.04–0.74; <i>p</i> = 0.01). <b>Conclusions</b>: 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 <i>bla</i><sub>AmpC</sub> 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.https://www.mdpi.com/2079-6382/14/3/322carbapenem-resistant <i>Pseudomonas aeruginosa</i>efflux pumpporinβ-lactamasemortalityrisk factors
spellingShingle Parichart Chotimakorn
Sutthiporn Pattharachayakul
Yongyut Lertsrisatit
Wichai Santimaleeworagun
Pimpimon Tansakul
Mingkwan Yingkajorn
Sureerat Chelae
Rattanaruji Pomwised
Arnon Chukamnerd
Rosesathorn Soontarach
Sarunyou Chusri
Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
Antibiotics
carbapenem-resistant <i>Pseudomonas aeruginosa</i>
efflux pump
porin
β-lactamase
mortality
risk factors
title Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
title_full Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
title_fullStr Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
title_full_unstemmed Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
title_short Antimicrobial Resistance and Mortality in Carbapenem-Resistant <i>Pseudomonas aeruginosa</i> Infections in Southern Thailand
title_sort antimicrobial resistance and mortality in carbapenem resistant i pseudomonas aeruginosa i infections in southern thailand
topic carbapenem-resistant <i>Pseudomonas aeruginosa</i>
efflux pump
porin
β-lactamase
mortality
risk factors
url https://www.mdpi.com/2079-6382/14/3/322
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