ArticleThe Journal of antimicrobial chemotherapy2022
In vivo translational assessment of the GES genotype on the killing profile of ceftazidime, ceftazidime/avibactam and meropenem against Pseudomonas aeruginosa.
Article in The Journal of antimicrobial chemotherapy, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 9 papers.
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Who cites it
9 citing papers in PubMed, 15 citations in OpenAlex.
- Comment on: An improved algorithm to screen for carbapenemase production inJAC-antimicrobial resistance · 2026Article
- Current and future options for the treatment of serious infections due to carbapenem-resistantClinical microbiology reviews · 2025Review
- Screening macrocyclic peptide libraries by yeast display allows control of selection process and affinity ranking.Nature communications · 2025Article
- Dose optimization of piperacillin/tazobactam, cefepime, and ceftazidime for carbapenem-resistant Pseudomonas aeruginosa isolates in Türkiye.European journal of clinical microbiology & infectious diseases : official publication of the European Society of Clinical Microbiology · 2025Article
- Mechanisms leading toAntimicrobial agents and chemotherapy · 2024Article
- Assessing the in vivo efficacy of rational antibiotics and combinations against difficult-to-treat Pseudomonas aeruginosa producing GES β-lactamases.The Journal of antimicrobial chemotherapy · 2023Article
- Article
- In vivo efficacy & resistance prevention of cefiderocol in combination with ceftazidime/avibactam, ampicillin/sulbactam or meropenem using human-simulated regimens versus Acinetobacter baumannii.The Journal of antimicrobial chemotherapy · 2023Article
- Phenotypic and genotypic profile of ceftolozane/tazobactam-non-susceptible, carbapenem-resistant Pseudomonas aeruginosa.The Journal of antimicrobial chemotherapy · 2022Article
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Authors and funding
4 authors at 2 institutions in 2 countries.
Funding
Abstract
objectivesTo evaluate the in vivo killing profile of human-simulated exposures of ceftazidime, ceftazidime/avibactam and meropenem against GES-harbouring Pseudomonas aeruginosa in the murine thigh infection model.
methodsFive P. aeruginosa isolates [three isogenic (GES-1, GES-5 and GES-15) and two clinical (GES-5 and GES-15)] were evaluated. MICs were determined using broth microdilution. Human-simulated regimens (HSRs) of ceftazidime 2 g IV q8h as a 2 h infusion, ceftazidime/avibactam 2.5 g IV q8h as a 2 h infusion and meropenem 2 g IV q8h as a 3 h infusion were administered. Change in bacterial burden relative to baseline was assessed.
resultsModal MICs ranged from 8 to >64 mg/L for ceftazidime, from 1 to 16 mg/L for ceftazidime/avibactam and from 1 to >64 mg/L for meropenem. In vivo, for the isogenic strains, avibactam augmented ceftazidime activity against the GES-1- and GES-15-harbouring isolates. Both ceftazidime and ceftazidime/avibactam resulted in significant kill against the GES-5 isogenic isolate. The meropenem HSR produced >1 log10 kill against each isogenic isolate (MICs of 1-4 mg/L). Against the GES-5 clinical isolate, ceftazidime and ceftazidime/avibactam resulted in >1 log10 kill compared with bacterial growth with the meropenem HSR. In the clinical isolate harbouring GES-15, the elevated MICs of ceftazidime and ceftazidime/avibactam reduced the effectiveness of both compounds, while the observed reduction in meropenem MIC translated into in vivo efficacy of the HSR regimen, predictive of clinical efficacy.
conclusionsIn GES-harbouring P. aeruginosa, quantitative reductions in bacterial density observed with the translational murine model suggest that the phenotypic profile of ceftazidime, ceftazidime/avibactam and meropenem is predictive of clinical efficacy when using the evaluated dosing regimens.
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