Phenotypic convergence and collateral susceptibility development in Pseudomonas aeruginosa under antibiotic exposure in ICU patients

Antibiotic combination therapy is often used to broaden the antimicrobial spectrum, limit resistance and improve treatment efficacy. Several antibiotics show collateral effects where resistance to one antibiotic increases susceptibility to another. In intensive care units (ICUs), antibiotic treatments are frequently adjusted based on patient outcomes, without considering collateral effects. This provides a setting to study these effects in Pseudomonas aeruginosa (PA), a highly adaptable, multidrug-resistant (MDR), nosocomial pathogen. We compared longitudinal PA isolates from twenty-five ventilated ICU patients receiving various antibiotics to laboratory strains undergoing in vitro adaptive evolution under four antipseudomonal monotherapies. Prolonged exposure to certain antibiotics produced resistance with collateral effects. In vitro, increasing antibiotic pressure drove distinct mutational trajectories. In patients, the number of antibiotics administered did not correlate with resistance changes to those antibiotics, suggesting that switching may reduce persistence of resistance. Notably, an inverse correlation between resistance to non-administered antibiotics and the number of different antibiotic classes administered, aligns with the principles of collateral susceptibility driven by multi-class exposure. This study provides s real-world evidence that empirical antibiotic mixing in ICU patients leverages evolutionary trade-offs. Consequently, diversifying antibiotic pressure via multi-class exposure may attenuate the fixation and persistence of MDR phenotypes in critical care.

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Publication Details

Journal
npj Antimicrobials and Resistance
Published
2026-05-08
DOI
https://doi.org/10.1038/s44259-026-00199-3
Primary Topic
Antibiotic Resistance in Bacteria
Type
article
Field-Weighted Citation Impact
0.00

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article

Phenotypic convergence and collateral susceptibility development in Pseudomonas aeruginosa under antibiotic exposure in ICU patients

A. Temelkov, Y. Glupczynski, B. Suberviola-Cañas, Basil Britto Xavier et al.
npj Antimicrobials and Resistance
Antibiotic Resistance in Bacteria
article

Phenotypic convergence and collateral susceptibility development in Pseudomonas aeruginosa under antibiotic exposure in ICU patients

A. Temelkov, Y. Glupczynski, B. Suberviola-Cañas, Basil Britto Xavier, Elisabeth De Waele, Darren Troeman, Vincent Huberlant, E. Odisseeva, P. Depuydt, Denise van Hout, Leen Timbermont, Jaromír Vajter, Jasmine Coppens, Sandra Long, Michael Joannidis, Surbhi Malhotra‐Kumar, Cenk Kıraklı, Ángel Arenzana-Seisdedos, Jacques Devriendt, Kadri Tamme, David E. Tabor, Craig MacLean, Claudia Recanatini, Cristina Prat, Thilo Köhler, Kumar-Singh Samir, Michal Hanauer, Matilda Berkell, J Chastre, Jasminka Kopić, Alain Lepape, Tuba Vilken, Sam Van Boxstael, Kathryn Shoemaker, M. Fartoukh, İlkay Bozkurt, Miranda van Rijen, Nicolas De Schryver, Susanne Weber, Biljana Carević, Vladimír Šrámek, Jelle Vlaeminck, Tomas Hruby, Hürrem Bodur, Thomas van der Schalk, Martin Wolkewitz, Walter Klimscha, Róbert Jurkinya, Gaëtan Plantefève, Mark T. Esser, R Vatcheva, Mladen Perić, Iványi Zsolt, Derek Hazard, Omar Ali, Frank Coenjaerts, Olaf Cremer, Jan A.J.W. Kluytmans, Marc J. M. Bonten, Sebastian Hullegie, Antonio DiGiandomenico, Daniel Prins, Marc Bourgeois, Iftihar Koksal, Rubana Kalyani, An Hottebeekx, Jasna Jevdjić, Alexey Ruzin, Achim Kaasch, Christine Lammens, Thomas E. van der Schalk, Evelina Tacconelli, Epaminondas Zakynthinos, Hasan Jafri, Miguel Sanchez Garcia, Dolores Escudero, Frangiscos Sifakis, Mickael Landais, the COMBACTE-MAGNET EVADE study group, Michal Drab, Herman Goossens, Galia Rahav, Bruno François, Apostolos Komnos, Fleur Paling, Antonio Oliver, Miguel Sánchez-García, On behalf of the ASPIRE-ICU study team
article en

Abstract

Antibiotic combination therapy is often used to broaden the antimicrobial spectrum, limit resistance and improve treatment efficacy. Several antibiotics show collateral effects where resistance to one antibiotic increases susceptibility to another. In intensive care units (ICUs), antibiotic treatments are frequently adjusted based on patient outcomes, without considering collateral effects. This provides a setting to study these effects in Pseudomonas aeruginosa (PA), a highly adaptable, multidrug-resistant (MDR), nosocomial pathogen. We compared longitudinal PA isolates from twenty-five ventilated ICU patients receiving various antibiotics to laboratory strains undergoing in vitro adaptive evolution under four antipseudomonal monotherapies. Prolonged exposure to certain antibiotics produced resistance with collateral effects. In vitro, increasing antibiotic pressure drove distinct mutational trajectories. In patients, the number of antibiotics administered did not correlate with resistance changes to those antibiotics, suggesting that switching may reduce persistence of resistance. Notably, an inverse correlation between resistance to non-administered antibiotics and the number of different antibiotic classes administered, aligns with the principles of collateral susceptibility driven by multi-class exposure. This study provides s real-world evidence that empirical antibiotic mixing in ICU patients leverages evolutionary trade-offs. Consequently, diversifying antibiotic pressure via multi-class exposure may attenuate the fixation and persistence of MDR phenotypes in critical care.

npj Antimicrobials and Resistance
Semmelweis University (HU), University of Geneva (CH), Izmir University (TR), University Hospital Centre Zagreb (HR), Innsbruck Medical University (AT), University of Antwerp (BE), Inserm (FR), Karadeniz Technical University (TR), Universität Innsbruck (AT), Utrecht University (NL), Ondokuz Mayıs University (TR), Alexandrovska Hospital (BG), Sheba Medical Center (IL), Ghent University Hospital (BE), University Medical Center Freiburg (DE), Queen Giovanna Hospital (BG), Tartu University Hospital (EE), Hospital Clínico San Carlos (ES), University Medical Center Utrecht (NL), Donauspital (AT), Sorbonne Université (FR), University of Oxford (GB), Hospital Universitario Virgen Macarena (ES), Clinique Saint Pierre (BE), Universitätsklinikum Tübingen (DE), University Hospital in Motol (CZ), Marqués de Valdecilla University Hospital (ES), University Hospital Brno (CZ), Centre Hospitalier Universitaire Brugmann (BE), Amphia Ziekenhuis (NL), University Hospital of Larissa (GR), Hôpital de Jolimont (BE), Ankara Numune Eğitim ve Araştırma Hastanesi (TR), AstraZeneca (Australia) (AU), AstraZeneca (France) (FR), Centar za Promociju Nauke (RS), Hôpital Lyon Sud (FR), Military Medical Academy (BG), Infectious Diseases Institute (UG), Centre Hospitalier Universitaire de Limoges (FR), AZ Sint-Jan (BE), Centre Hospitalier du Mans (FR), Krajská Zdravotní (CZ), AstraZeneca (Japan) (JP), HSU Dr. Suat Seren Chest Diseases and Chest Surgery Training and Research Hospital (TR), Hospital Universitario Central de Asturias (ES), Centre Hospitalier Victor Dupouy (FR), AstraZeneca (Poland) (PL), St. Anne's University Hospital Brno (CZ), AstraZeneca (Finland) (FI), Gilead Sciences (United States) (US), Regional Museum in Teplice (CZ), University of Slavonski Brod (HR), Ziekenhuis Oost-Limburg (BE), Jósa András Múzeum (HU), AstraZeneca (United States) (US), Hospital Universitario Son Espases (ES), Hospital Universitari Germans Trias i Pujol (ES), Clinical Centre of Kragujevac (RS), Royal Blackburn Teaching Hospital (GB), Hôpital Tenon (FR), Université de Limoges (FR), Otto-von-Guericke-Universität Magdeburg (DE)
European Federation of Pharmaceutical Industries and Associations, European Commission, Innovative Medicines Initiative
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Openalex Percentile: Top 11%
Antibiotic Resistance in Bacteria
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