ArticleScientific reports2017
Mechanisms of intrinsic resistance and acquired susceptibility of Pseudomonas aeruginosa isolated from cystic fibrosis patients to temocillin, a revived antibiotic.
Article in Scientific reports, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.
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22 citing papers in PubMed, 43 citations in OpenAlex.
- AMR-GNN: a multi-representation graph neural network framework to enable genomic antimicrobial resistance prediction.Nature communications · 2026Article
- Understanding Drug Permeability inLife (Basel, Switzerland) · 2025Review
- Temocillin: A Narrative Review of Its Clinical Reappraisal.Antibiotics (Basel, Switzerland) · 2025Review
- CombattingAntibiotics (Basel, Switzerland) · 2025Review
- Temocillin Resistance in the Enterobacter cloacae Complex Is Conferred by a Single Point Mutation in BaeS, Leading to Overexpression of the AcrD Efflux Pump.Antimicrobial agents and chemotherapy · 2023Article
- Assessing Clinical Potential of Old Antibiotics against Severe Infections by Multi-Drug-Resistant Gram-Negative Bacteria Using In Silico Modelling.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Temocillin: Applications in Antimicrobial Stewardship as a Potential Carbapenem-Sparing Antibiotic.Antibiotics (Basel, Switzerland) · 2022Review
- Activity of temocillin against third-generation cephalosporin-resistantJAC-antimicrobial resistance · 2022Article
- Role of the multi-drug efflux systems on the baseline susceptibility to ceftazidime/avibactam and ceftolozane/tazobactam in clinical isolates of non-carbapenemase-producing carbapenem-resistantFrontiers in pharmacology · 2022Article
- β-lactam Resistance inPathogens (Basel, Switzerland) · 2021Review
- Occurrence of NDM-1 and VIM-2 Co-ProducingDiagnostics (Basel, Switzerland) · 2021Article
- The Polyaminoisoprenyl Potentiator NV716 Revives Old Disused Antibiotics against Intracellular Forms of Infection by Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2021Article
- Adaptation to the cervical environment is associated with increased antibiotic susceptibility in Neisseria gonorrhoeae.Nature communications · 2020Article
- Identification and characterization of phage protein and its activity against two strains of multidrug-resistant Pseudomonas aeruginosa.Scientific reports · 2019Article
- Resurrecting Old β-Lactams: Potent Inhibitory Activity of Temocillin against Multidrug-ResistantAntimicrobial agents and chemotherapy · 2019Article
- Target (MexB)- and Efflux-Based Mechanisms Decreasing the Effectiveness of the Efflux Pump Inhibitor D13-9001 inAntimicrobial agents and chemotherapy · 2019Article
- Pharmacokinetics and Pharmacodynamics of Temocillin.Clinical pharmacokinetics · 2018Review
- Article
- Great phenotypic and genetic variation among successive chronic Pseudomonas aeruginosa from a cystic fibrosis patient.PloS one · 2018Article
- Understanding antibiotic resistance via outer membrane permeability.Infection and drug resistance · 2018Review
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Authors and funding
13 authors at 7 institutions in 4 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The β-lactam antibiotic temocillin (6-α-methoxy-ticarcillin) shows stability to most extended spectrum β-lactamases, but is considered inactive against Pseudomonas aeruginosa. Mutations in the MexAB-OprM efflux system, naturally occurring in cystic fibrosis (CF) isolates, have been previously shown to reverse this intrinsic resistance. In the present study, we measured temocillin activity in a large collection (n = 333) of P. aeruginosa CF isolates. 29% of the isolates had MICs ≤ 16 mg/L (proposed clinical breakpoint for temocillin). Mutations were observed in mexA or mexB in isolates for which temocillin MIC was ≤512 mg/L (nucleotide insertions or deletions, premature termination, tandem repeat, nonstop, and missense mutations). A correlation was observed between temocillin MICs and efflux rate of N-phenyl-1-naphthylamine (MexAB-OprM fluorescent substrate) and extracellular exopolysaccharide abundance (contributing to a mucoid phenotype). OpdK or OpdF anion-specific porins expression decreased temocillin MIC by ~1 two-fold dilution only. Contrarily to the common assumption that temocillin is inactive on P. aeruginosa, we show here clinically-exploitable MICs on a non-negligible proportion of CF isolates, explained by a wide diversity of mutations in mexA and/or mexB. In a broader context, this work contributes to increase our understanding of MexAB-OprM functionality and help delineating how antibiotics interact with MexA and MexB.
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