Evidence map›Paper›PMID 41361747›Full record

ArticleBMC microbiology2025

Deciphering the emergence of mutations in Pseudomonas aeruginosa after ceftolozane/tazobactam treatment and evaluating therapeutic alternatives.

Léa Bientz, Hugo Boijout, Raoudha Grami, Ulysse Guyet, Marin Lahouati, Melissande Hertzmann, Antony Marques, Audrey Toirot, Sabine Aillerie, Laure Coulange-Mayonnove and 4 more

Abstract read
In one paragraph

Article in BMC microbiology, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it
0cells of the map it votes in
0citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Léa BientzUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Hugo BoijoutUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Raoudha GramiUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Ulysse GuyetUniv. Bordeaux, Bordeaux Bioinformatics Center (CBiB), Bordeaux , 33000, France.
Marin LahouatiClinical Pharmacy Department, Bordeaux University Hospital, Bordeaux, 33000, France.
Melissande HertzmannUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Antony MarquesUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Audrey ToirotUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Sabine AillerieUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Laure Coulange-MayonnoveUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Alexis GroppiUniv. Bordeaux, Bordeaux Bioinformatics Center (CBiB), Bordeaux , 33000, France.
Macha NikolskiUniv. Bordeaux, Bordeaux Bioinformatics Center (CBiB), Bordeaux , 33000, France.
Cécile BébéarUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France.
Véronique DuboisUniv. Bordeaux, CNRS, Microbiologie Fondamentale et Pathogénicité (MFP), UMR5234, ARMYNE Team, 2 Rue Hoffmann Martinot - Bât Bordeaux Biologie Santé, Bordeaux, 33000, France. veronique.dubois@u-bordeaux.fr.

Funding

Joint Programming Initiative on Antimicrobial Resistance MAGITICS_JPIAMR_2019_P011
6 · The paper itself

Abstract

objectivesCeftolozane/tazobactam is a relevant option for treating multiresistant Pseudomonas aeruginosa, a major public health problem. Over a 14-month period, we studied the frequency of ceftolozane/tazobactam resistance development and mechanisms underlying resistance in P. aeruginosa isolates after ceftolozane/tazobactam treatment as well as alternative therapeutic options.

methodsAntimicrobial susceptibility was assessed with the disc diffusion method and minimum inhibitory concentration (MIC) determination. Resistance genes and sequence types (ST) were determined by whole genome sequencing (WGS). The ceftolozane/tazobactam resistance mechanism was explored by cloning ampC into the ampC-deficient strain PAO1 and bla

resultsOf 50 patients treated, 9 (18%) acquired one or more ceftolozane/tazobactam-resistant isolates during treatment. WGS revealed various mutations in the ampC gene, namely, Thr70Ile, Phe121Leu, Pro154Leu, Gly157Asp, del210-216, Glu221Lys, and the new mutation, Pro217Gln. Cloning experiments revealed that the Pseudomonas-derived cephalosporinase (PDC) polymorphism did not alter mutation effects, mutations did not confer the same resistance level, and those conferring the strongest resistance restored susceptibility to piperacillin, piperacillin/tazobactam and imipenem despite changes in the oprD gene. In clinical isolates, the resistance level conferred by the same mutations differed, indicating the involvement of other mechanisms, particularly the overproduction of AmpC, which is always present due to mutations mainly in AmpD. Finally, imipenem/relebactam, colistin, amikacin and cefiderocol could be good alternatives for treating ceftolozane/tazobactam-resistant strains. CONCLUTION: Ceftolozane/tazobactam resistance development was associated mainly with chromosomal mutations in the ampC gene but also with mutations in its regulatory genes. Knowledge about these mutations and gene polymorphisms is essential for interpreting resistance phenotypes from genomic data.

Indexed as

Anti-Bacterial AgentsCephalosporinsDrug Resistance, Multiple, BacterialMutationPseudomonas aeruginosaPseudomonas InfectionsTazobactamBacterial Proteinsbeta-LactamasesHumansMicrobial Sensitivity TestsWhole Genome SequencingAmpC beta-lactamasesAnti-Bacterial AgentsBacterial Proteinsbeta-Lactamasesceftolozaneceftolozane, tazobactam drug combinationCephalosporinsTazobactamCeftolozane/tazobactamCephalosporinaseMultidrug resistanceNew antibioticsPseudomonas aeruginosa

Identifiers

PMID41361747
PMCPMC12801942

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.