ArticleThe Journal of infectious diseases2015
Combination treatment with meropenem plus levofloxacin is synergistic against Pseudomonas aeruginosa infection in a murine model of pneumonia.
Article in The Journal of infectious diseases, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers, 1 of them a synthesis 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.
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Who cites it
23 citing papers in PubMed, 1 synthesis or guideline pooled it, 36 citations in OpenAlex.
- 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
- Pharmacokinetic-pharmacodynamic modeling to evaluate the relative impact of immune response and meropenem on bacterial killingAntimicrobial agents and chemotherapy · 2026Article
- Lower respiratory tract microbiota characteristics in patients withFrontiers in cellular and infection microbiology · 2026Article
- Critical role of growth medium for detecting drug interactions in Gram-negative bacteria that modelmBio · 2024Article
- Aerosolized delivery of ESKAPE pathogens for murine pneumonia models.Scientific reports · 2024Article
- Evaluating Mono- and Combination Therapy of Meropenem and Amikacin against Pseudomonas aeruginosa Bacteremia in the Hollow-Fiber Infection Model.Microbiology spectrum · 2022Article
- Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents.Frontiers in microbiology · 2022Review
- Article
- Fluoroquinolone-Transition Metal Complexes: A Strategy to Overcome Bacterial Resistance.Microorganisms · 2021Review
- Building Optimal Three-Drug Combination Chemotherapy Regimens.Antimicrobial agents and chemotherapy · 2020Article
- Efficacy of Ceftolozane-Tazobactam in Combination with Colistin against Extensively Drug-Resistant Pseudomonas aeruginosa, Including High-Risk Clones, in anAntimicrobial agents and chemotherapy · 2020Article
- When One Drug Is Not Enough: Context, Methodology, and Future Prospects in Antibacterial Synergy Testing.Clinics in laboratory medicine · 2019Review
- Emergence of antibiotic resistanceGenes & diseases · 2019Review
- The Combination of Fosfomycin plus Meropenem Is Synergistic for Pseudomonas aeruginosa PAO1 in a Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2018Article
- Therapies for multidrug resistant and extensively drug-resistant non-fermenting gram-negative bacteria causing nosocomial infections: a perilous journey toward 'molecularly targeted' therapy.Expert review of anti-infective therapy · 2018Review
- The quick loss of carbapenem susceptibility in Pseudomonas aeruginosa at intensive care units.International journal of clinical pharmacy · 2018Observational
- Evaluation of Pharmacokinetic/Pharmacodynamic Model-Based Optimized Combination Regimens against Multidrug-Resistant Pseudomonas aeruginosa in a Murine Thigh Infection Model by Using Humanized Dosing Schemes.Antimicrobial agents and chemotherapy · 2017Article
- The Nonantibiotic Macrolide EM703 Improves Survival in a Model of Quinolone-Treated Pseudomonas aeruginosa Airway Infection.Antimicrobial agents and chemotherapy · 2017Article
- Substantial Impact of Altered Pharmacokinetics in Critically Ill Patients on the Antibacterial Effects of Meropenem Evaluated via the Dynamic Hollow-Fiber Infection Model.Antimicrobial agents and chemotherapy · 2017Article
- Article
Corrections and comments
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Authors and funding
12 authors at 2 institutions in 1 country.
Funding
Abstract
backgroundMeropenem plus levofloxacin treatment was shown to be a promising combination in our in vitro hollow fiber infection model. We strove to validate this finding in a murine Pseudomonas pneumonia model.
methodsA dose-ranging study with meropenem and levofloxacin alone and in combination against Pseudomonas aeruginosa was performed in a granulocytopenic murine pneumonia model. Meropenem and levofloxacin were administered to partially humanize their pharmacokinetic profiles in mouse serum. Total and resistant bacterial populations were estimated after 24 hours of therapy. Pharmacokinetic profiling of both drugs was performed in plasma and epithelial lining fluid, using a population model.
resultsMeropenem and levofloxacin penetrations into epithelial lining fluid were 39.3% and 64.3%, respectively. Both monotherapies demonstrated good exposure responses. An innovative combination-therapy analytic approach demonstrated that the combination was statistically significantly synergistic (α = 2.475), as was shown in the hollow fiber infection model. Bacterial resistant to levofloxacin and meropenem was seen in the control arm. Levofloxacin monotherapy selected for resistance to itself. No resistant subpopulations were observed in any combination therapy arm.
conclusionsThe combination of meropenem plus levofloxacin was synergistic, producing good bacterial kill and resistance suppression. Given the track record of safety of each agent, this combination may be worthy of clinical trial.
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