ArticleAntimicrobial agents and chemotherapy2005
Optimization of meropenem minimum concentration/MIC ratio to suppress in vitro resistance of Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. It is linked to trial NCT03440216 (Population Pharmacokinetics and Pharmacodynamics of Beta-lactams of Interest in Adult Patients From Intensive Care Units), which is not on this map. Cited by 99 papers, 3 of them syntheses that pooled it.
What it found
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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.
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.
Population Pharmacokinetics and Pharmacodynamics of Beta-lactams of Interest in Adult Patients From Intensive Care Units
Who cites it
99 citing papers in PubMed, 3 syntheses or guidelines pooled it, 195 citations in OpenAlex.
- Addition of probenecid to oral β-lactam antibiotics: a systematic review and meta-analysis.The Journal of antimicrobial chemotherapy · 2022Pooled it
- Prolonged Versus Intermittent Infusion of β-Lactam Antibiotics: A Systematic Review and Meta-Regression of Bacterial Killing in Preclinical Infection Models.Clinical pharmacokinetics · 2020Pooled it
- What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.Clinical pharmacokinetics · 2019Pooled it
- Intrapulmonary concentrations of meropenem administered by continuous infusion in critically ill patients with nosocomial pneumonia: a randomized pharmacokinetic trial.Critical care (London, England) · 2020Trial
- Short versus long infusion of meropenem in very-low-birth-weight neonates.Antimicrobial agents and chemotherapy · 2012Trial
- Clinical and microbiological efficacy of continuous versus intermittent application of meropenem in critically ill patients: a randomized open-label controlled trial.Critical care (London, England) · 2012Trial
- Meropenem pharmacokinetics in the newborn.Antimicrobial agents and chemotherapy · 2009Trial
- Randomized, open-label, comparative study of piperacillin-tazobactam administered by continuous infusion versus intermittent infusion for treatment of hospitalized patients with complicated intra-abdominal infection.Antimicrobial agents and chemotherapy · 2006Trial
- Article
- PaVarDB: a database and web platform for missense variant analysis in Pseudomonas aeruginosa using an end-to-end BVbase pipeline.Database : the journal of biological databases and curation · 2026Article
- Beta-Lactam Antibiotic Concentrations and the Acquisition of Multi-Drug Resistant Bacteria in Critically Ill Patients.Life (Basel, Switzerland) · 2025Article
- Antibacterial activity and mechanism of Sodium houttuyfonate against heteroresistantFrontiers in microbiology · 2025Article
- Pharmacokinetic-pharmacodynamic target attainment analyses as support for meropenem dosing regimens in critically ill adult and elderly patients withFrontiers in pharmacology · 2025Article
- Understanding antimicrobial pharmacokinetics in critically ill patients to optimize antimicrobial therapy: A narrative review.Journal of intensive medicine · 2024Review
- Challenges for global antibiotic regimen planning and establishing antimicrobial resistance targets: implications for the WHO Essential Medicines List and AWaRe antibiotic book dosing.Clinical microbiology reviews · 2024Review
- Simulated drug disposition in critically ill patients to evaluate effective PK/PD targets for combatingAntimicrobial agents and chemotherapy · 2024Article
- Assessment of antibiotic release and antibacterial efficacy from pendant glutathione hydrogels using ex vivo porcine skin.Journal of controlled release : official journal of the Controlled Release Society · 2024Article
- Pharmacokinetic/pharmacodynamic issues for optimizing treatment with beta-lactams of Gram-negative infections in critically ill orthotopic liver transplant recipients: a comprehensive review.Frontiers in antibiotics · 2024Review
- Impact of Various Estimated Glomerular Filtration Rate Equations on the Pharmacokinetics of Meropenem in Critically Ill Adults.Critical care explorations · 2023Article
- Antimicrobial Multidrug Resistance: Clinical Implications for Infection Management in Critically Ill Patients.Microorganisms · 2023Review
39 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
6 authors at 3 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Suppression of resistance in a dense Pseudomonas aeruginosa population has previously been shown with optimized quinolone exposures. However, the relevance to beta-lactams is unknown. We investigated the bactericidal activity of meropenem and its propensity to suppress P. aeruginosa resistance in an in vitro hollow-fiber infection model (HFIM). Two isogenic strains of P. aeruginosa (wild type and an AmpC stably derepressed mutant [MIC = 1 mg/liter]) were used. An HFIM inoculated with approximately 1 x 10(8) CFU/ml of bacteria was subjected to various meropenem exposures. Maintenance doses were given every 8 h to simulate the maximum concentration achieved after a 1-g dose in all regimens, but escalating unbound minimum concentrations (C(min)s) were simulated with different clearances. Serial samples were obtained over 5 days to quantify the meropenem concentrations, the total bacterial population, and subpopulations with reduced susceptibilities to meropenem (>3x the MIC). For both strains, a significant bacterial burden reduction was seen with all regimens at 24 h. Regrowth was apparent after 3 days, with the C(min)/MIC ratio being < or = 1.7 (time above the MIC, 100%). Selective amplification of subpopulations with reduced susceptibilities to meropenem was suppressed with a C(min)/MIC of > or = 6.2 or by adding tobramycin to meropenem (C(min)/MIC = 1.7). Investigations that were longer than 24 h and that used high inocula may be necessary to fully evaluate the relationship between drug exposures and the likelihood of resistance suppression. These results suggest that the C(min)/MIC of meropenem can be optimized to suppress the emergence of non-plasmid-mediated P. aeruginosa resistance. Our in vitro data support the use of an extended duration of meropenem infusion for the treatment of severe nosocomial infections in combination with an aminoglycoside.
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Registered trials
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.