Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital

BackgroundCeftolozane/tazobactam (C/T) was temporarily withdrawn from December 2020 to February 2022: this forced unavailability created the conditions to study how drug discontinuation might influence Pseudomonas aeruginosa (PA) resistance reversibility in a real-life setting.MethodsClinically rele...

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Main Authors: Alessandra Imeneo, Laura Campogiani, Pietro Vitale, Andrea Di Lorenzo, Grazia Alessio, Davide Natale Abate, Maria Grazia Celeste, Anna Altieri, Cartesio D’Agostini, Vincenzo Malagnino, Massimo Andreoni, Marco Iannetta, Loredana Sarmati
Format: Article
Language:English
Published: Frontiers Media S.A. 2025-04-01
Series:Frontiers in Microbiology
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Online Access:https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542491/full
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author Alessandra Imeneo
Laura Campogiani
Laura Campogiani
Pietro Vitale
Andrea Di Lorenzo
Andrea Di Lorenzo
Grazia Alessio
Davide Natale Abate
Maria Grazia Celeste
Anna Altieri
Cartesio D’Agostini
Cartesio D’Agostini
Vincenzo Malagnino
Vincenzo Malagnino
Massimo Andreoni
Massimo Andreoni
Marco Iannetta
Marco Iannetta
Loredana Sarmati
Loredana Sarmati
author_facet Alessandra Imeneo
Laura Campogiani
Laura Campogiani
Pietro Vitale
Andrea Di Lorenzo
Andrea Di Lorenzo
Grazia Alessio
Davide Natale Abate
Maria Grazia Celeste
Anna Altieri
Cartesio D’Agostini
Cartesio D’Agostini
Vincenzo Malagnino
Vincenzo Malagnino
Massimo Andreoni
Massimo Andreoni
Marco Iannetta
Marco Iannetta
Loredana Sarmati
Loredana Sarmati
author_sort Alessandra Imeneo
collection DOAJ
description BackgroundCeftolozane/tazobactam (C/T) was temporarily withdrawn from December 2020 to February 2022: this forced unavailability created the conditions to study how drug discontinuation might influence Pseudomonas aeruginosa (PA) resistance reversibility in a real-life setting.MethodsClinically relevant PA isolates collected between January 1st 2019 and February 22nd 2023 with a C/T susceptibility test available were included. Changes in PA antibiotic susceptibility towards C/T and other antibiotics were examined in three different periods (period A, March–December 2019 and March–December 2020, C/T available; period B, March–December 2021, C/T withdrawn; period C, March–December 2022, C/T reintroduced), also considering the overall consumption rate through the Defined Daily Dose per 100 bed-days per year.ResultsSeven hundred and fifty-one PA isolates were included. A statistically significant reduction of C/T resistance rate was observed when C/T became unavailable, followed by a subsequent increase with its reintroduction (period A 25.1% vs. period B 5.3% vs. period C 10.0%, p < 0.001). A concomitant reduction of resistance rates towards other antibiotics was recorded, consistent with antibiotic consumptions and antimicrobial stewardship programs implementation. A subgroup of 22 patients presented a C/T-resistant isolate after a previous susceptible one; only 4 patients had received a prior C/T treatment.ConclusionThe unavailability of C/T created the conditions to analyze the practical application of the theory of fitness cost to maintain resistance. A subsequent increase after a first reduction in C/T resistance rate was observed, probably due to persistence of resistant isolates and antibiotic selective pressure. Continuous monitoring of antibiotic use and evolving resistance is essential.
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spelling doaj-art-f00edebe7bbf4d2eb42b3e7243a6b8da2025-08-20T03:10:32ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2025-04-011610.3389/fmicb.2025.15424911542491Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospitalAlessandra Imeneo0Laura Campogiani1Laura Campogiani2Pietro Vitale3Andrea Di Lorenzo4Andrea Di Lorenzo5Grazia Alessio6Davide Natale Abate7Maria Grazia Celeste8Anna Altieri9Cartesio D’Agostini10Cartesio D’Agostini11Vincenzo Malagnino12Vincenzo Malagnino13Massimo Andreoni14Massimo Andreoni15Marco Iannetta16Marco Iannetta17Loredana Sarmati18Loredana Sarmati19Department of System Medicine, University of Rome Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyHospital Pharmacy, Policlinico Tor Vergata, Rome, ItalyHospital Pharmacy, Policlinico Tor Vergata, Rome, ItalyLaboratory of Clinical Microbiology, Policlinico Tor Vergata, Rome, ItalyLaboratory of Clinical Microbiology, Policlinico Tor Vergata, Rome, ItalyDepartment of Experimental Medicine, University of Rome Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyDepartment of System Medicine, University of Rome Tor Vergata, Rome, ItalyInfectious Disease Clinic, Policlinico Tor Vergata, Rome, ItalyBackgroundCeftolozane/tazobactam (C/T) was temporarily withdrawn from December 2020 to February 2022: this forced unavailability created the conditions to study how drug discontinuation might influence Pseudomonas aeruginosa (PA) resistance reversibility in a real-life setting.MethodsClinically relevant PA isolates collected between January 1st 2019 and February 22nd 2023 with a C/T susceptibility test available were included. Changes in PA antibiotic susceptibility towards C/T and other antibiotics were examined in three different periods (period A, March–December 2019 and March–December 2020, C/T available; period B, March–December 2021, C/T withdrawn; period C, March–December 2022, C/T reintroduced), also considering the overall consumption rate through the Defined Daily Dose per 100 bed-days per year.ResultsSeven hundred and fifty-one PA isolates were included. A statistically significant reduction of C/T resistance rate was observed when C/T became unavailable, followed by a subsequent increase with its reintroduction (period A 25.1% vs. period B 5.3% vs. period C 10.0%, p < 0.001). A concomitant reduction of resistance rates towards other antibiotics was recorded, consistent with antibiotic consumptions and antimicrobial stewardship programs implementation. A subgroup of 22 patients presented a C/T-resistant isolate after a previous susceptible one; only 4 patients had received a prior C/T treatment.ConclusionThe unavailability of C/T created the conditions to analyze the practical application of the theory of fitness cost to maintain resistance. A subsequent increase after a first reduction in C/T resistance rate was observed, probably due to persistence of resistant isolates and antibiotic selective pressure. Continuous monitoring of antibiotic use and evolving resistance is essential.https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542491/fullceftolozane/tazobactamPseudomonas aeruginosafitness-costresistanceantibiotic susceptibility testing
spellingShingle Alessandra Imeneo
Laura Campogiani
Laura Campogiani
Pietro Vitale
Andrea Di Lorenzo
Andrea Di Lorenzo
Grazia Alessio
Davide Natale Abate
Maria Grazia Celeste
Anna Altieri
Cartesio D’Agostini
Cartesio D’Agostini
Vincenzo Malagnino
Vincenzo Malagnino
Massimo Andreoni
Massimo Andreoni
Marco Iannetta
Marco Iannetta
Loredana Sarmati
Loredana Sarmati
Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
Frontiers in Microbiology
ceftolozane/tazobactam
Pseudomonas aeruginosa
fitness-cost
resistance
antibiotic susceptibility testing
title Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
title_full Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
title_fullStr Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
title_full_unstemmed Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
title_short Ceftolozane/tazobactam use and emergence of resistance: a 4-year analysis of antimicrobial susceptibility in Pseudomonas aeruginosa isolates in a tertiary hospital
title_sort ceftolozane tazobactam use and emergence of resistance a 4 year analysis of antimicrobial susceptibility in pseudomonas aeruginosa isolates in a tertiary hospital
topic ceftolozane/tazobactam
Pseudomonas aeruginosa
fitness-cost
resistance
antibiotic susceptibility testing
url https://www.frontiersin.org/articles/10.3389/fmicb.2025.1542491/full
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