ArticleAntimicrobial agents and chemotherapy2007
Development of resistance in wild-type and hypermutable Pseudomonas aeruginosa strains exposed to clinical pharmacokinetic profiles of meropenem and ceftazidime simulated in vitro.
Article in Antimicrobial agents and chemotherapy, 2007. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 15 papers.
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15 citing papers in PubMed, 29 citations in OpenAlex.
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- Calculated initial parenteral treatment of bacterial infections: Pharmacokinetics and pharmacodynamics.GMS infectious diseases · 2020Article
- Evaluation of Tobramycin and Ciprofloxacin as a Synergistic Combination Against HypermutablePharmaceutics · 2019Article
- [Therapeutic drug monitoring and individual dosing of antibiotics during sepsis : Modern or just "trendy"?]Medizinische Klinik, Intensivmedizin und Notfallmedizin · 2018Review
- Antibiotic selection in the treatment of acute invasive infections by Pseudomonas aeruginosa: Guidelines by the Spanish Society of Chemotherapy.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2018Review
- Development of Antibiotic Resistance during Simulated Treatment of Pseudomonas aeruginosa in Chemostats.PloS one · 2016Article
- Absorption Kinetics of Subcutaneously Administered Ceftazidime in Hypoperfused Guinea Pigs.Current therapeutic research, clinical and experimental · 2015Article
- The challenge of efflux-mediated antibiotic resistance in Gram-negative bacteria.Clinical microbiology reviews · 2015Review
- Fighting microbial drug resistance: a primer on the role of evolutionary biology in public health.Evolutionary applications · 2015Article
- Exposure to phages has little impact on the evolution of bacterial antibiotic resistance on drug concentration gradients.Evolutionary applications · 2014Article
- Adaptive and mutational resistance: role of porins and efflux pumps in drug resistance.Clinical microbiology reviews · 2012Review
- Phages limit the evolution of bacterial antibiotic resistance in experimental microcosms.Evolutionary applications · 2012Article
- Development and qualification of a pharmacodynamic model for the pronounced inoculum effect of ceftazidime against Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2009Article
- The Saudi Thoracic Society guidelines for diagnosis and management of noncystic fibrosis bronchiectasis.Annals of thoracic medicineArticle
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4 authors at 1 institution in 1 country.
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No grant is acknowledged in the PubMed record.
Abstract
In this study we investigated the interplay of antibiotic pharmacokinetic profiles and the development of mutation-mediated resistance in wild-type and hypermutable Pseudomonas aeruginosa strains. We used in vitro models simulating profiles of the commonly used therapeutic drugs meropenem and ceftazidime, two agents with high levels of antipseudomonal activity said to have different potentials for stimulating resistance development. During ceftazidime treatment of the wild-type strain (PAO1), fully resistant mutants overproducing AmpC were selected rapidly and they completely replaced wild-type cells in the population. During treatment with meropenem, mutants of PAO1 were not selected as rapidly and showed only intermediate resistance due to the loss of OprD. These mutants also replaced the parent strain in the population. During the treatment of the mutator P. aeruginosa strain with meropenem, the slowly selected mutants did not accumulate several resistance mechanisms but only lost OprD and did not completely replace the parent strain in the population. Our results indicate that the commonly used dosing regimens for meropenem and ceftazidime cannot avoid the selection of mutants of wild-type and hypermutable P. aeruginosa strains. For the treatment outcome, including the prevention of resistance development, it would be beneficial for the antibiotic concentration to remain above the mutant prevention concentration for a longer period of time than it does in present regimens.
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