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ORIGINAL RESEARCH article

Front. Microbiol.

Sec. Antimicrobials, Resistance and Chemotherapy

Volume 16 - 2025 | doi: 10.3389/fmicb.2025.1542491

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

Provisionally accepted
Alessandra Imeneo Alessandra Imeneo 1Laura Campogiani Laura Campogiani 1Pietro Vitale Pietro Vitale 2Andrea Di Lorenzo Andrea Di Lorenzo 1Grazia Alessio Grazia Alessio 1Davide Natale Abate Davide Natale Abate 2Maria Grazia Celeste Maria Grazia Celeste 2Anna Altieri Anna Altieri 2Cartesio D'Agostini Cartesio D'Agostini 2Vincenzo Malagnino Vincenzo Malagnino 1Massimo Andreoni Massimo Andreoni 1Marco Iannetta Marco Iannetta 1Loredana Sarmati Loredana Sarmati 1*
  • 1 University of Rome Tor Vergata, Roma, Italy
  • 2 Policlinico Tor Vergata, Rome, Lazio, Italy

The final, formatted version of the article will be published soon.

    Ceftolozane/tazobactam (C/T) was temporarily withdrawn from December 2020 to February 2022: this forced unavailability created the conditions to study how drug discontinuation might influence Pseudomonas aeruginosa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.Clinically relevant PA isolates collected between January 1 st 2019 and February 22 nd 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periods (period A, March-December 2019 and March-December 2020, C/T available; period B, March-December 2021,C/T withdrawn; period C, March-December 2022, C/T reintroduced), also considering the overall consumption rate through the Defined Daily Dose per 100 bed-days per year.Seven 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.The 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.

    Keywords: ceftolozane/tazobactam, Pseudomonas aeruginosa, fitness-cost, Resistance, AST (antibiotic susceptibility testing)

    Received: 09 Dec 2024; Accepted: 01 Apr 2025.

    Copyright: © 2025 Imeneo, Campogiani, Vitale, Di Lorenzo, Alessio, Abate, Celeste, Altieri, D'Agostini, Malagnino, Andreoni, Iannetta and Sarmati. This is an open-access article distributed under the terms of the Creative Commons Attribution License (CC BY). The use, distribution or reproduction in other forums is permitted, provided the original author(s) or licensor are credited and that the original publication in this journal is cited, in accordance with accepted academic practice. No use, distribution or reproduction is permitted which does not comply with these terms.

    * Correspondence: Loredana Sarmati, University of Rome Tor Vergata, Roma, Italy

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