ArticleAntimicrobial agents and chemotherapy2013
Impact of meropenem in combination with tobramycin in a murine model of Pseudomonas aeruginosa pneumonia.
Article in Antimicrobial agents and chemotherapy, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers, 2 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.
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Who cites it
26 citing papers in PubMed, 2 syntheses or guidelines pooled it, 41 citations in OpenAlex.
- In vivo studies on antibiotic combination for the treatment of carbapenem-resistant Gram-negative bacteria: a systematic review and meta-analysis protocol.BMJ open science · 2020Pooled it
- What Antibiotic Exposures Are Required to Suppress the Emergence of Resistance for Gram-Negative Bacteria? A Systematic Review.Clinical pharmacokinetics · 2019Pooled it
- Tobramycin enhancesProceedings of the National Academy of Sciences of the United States of America · 2026Article
- Evaluation of Aminoglycoside Dosing Regimens Adjusted for Renal Function and In Vitro Susceptibility Test Interpretive Criteria for Enterobacterales andOpen forum infectious diseases · 2025Article
- Population pharmacokinetics and humanized dosage regimens matching the peak, area, trough, and range of amikacin plasma concentrations in immune-competent murine bloodstream and lung infection models.Antimicrobial agents and chemotherapy · 2024Article
- Improved characterization of aminoglycoside penetration into human lung epithelial lining fluid via population pharmacokinetics.Antimicrobial agents and chemotherapy · 2024Article
- Article
- Variability of murine bacterial pneumonia models used to evaluate antimicrobial agents.Frontiers in microbiology · 2022Review
- Fusogenic porous silicon nanoparticles as a broad-spectrum immunotherapy against bacterial infections.Nanoscale horizons · 2021Article
- Pharmacodynamics of Meropenem against Acinetobacter baumannii in a Neutropenic Mouse Thigh Infection Model.Antimicrobial agents and chemotherapy · 2020Article
- Meropenem-Tobramycin Combination Regimens Combat Carbapenem-Resistant Pseudomonas aeruginosa in the Hollow-Fiber Infection Model Simulating Augmented Renal Clearance in Critically Ill Patients.Antimicrobial agents and chemotherapy · 2019Article
- Synergistic Meropenem-Tobramycin Combination Dosage Regimens against Clinical Hypermutable Pseudomonas aeruginosa at Simulated Epithelial Lining Fluid Concentrations in a Dynamic Biofilm Model.Antimicrobial agents and chemotherapy · 2019Article
- Pharmacokinetics/Pharmacodynamics of Vaborbactam, a Novel Beta-Lactamase Inhibitor, in Combination with Meropenem.Antimicrobial agents and chemotherapy · 2019Article
- Optimization and Evaluation of Piperacillin-Tobramycin Combination Dosage Regimens against Pseudomonas aeruginosa for Patients with Altered Pharmacokinetics via the Hollow-Fiber Infection Model and Mechanism-Based Modeling.Antimicrobial agents and chemotherapy · 2018Article
- Efficacy of Human-Simulated Exposures of Ceftolozane-Tazobactam Alone and in Combination with Amikacin or Colistin against Multidrug-Resistant Pseudomonas aeruginosa in anAntimicrobial 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
- 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
- Aminoglycoside Concentrations Required for Synergy with Carbapenems against Pseudomonas aeruginosa Determined via Mechanistic Studies and Modeling.Antimicrobial agents and chemotherapy · 2017Article
- Article
- White Paper: Developing Antimicrobial Drugs for Resistant Pathogens, Narrow-Spectrum Indications, and Unmet Needs.The Journal of infectious diseases · 2017Review
Corrections and comments
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Authors and funding
5 authors at 1 institution in 1 country.
Funding
Abstract
Pseudomonas aeruginosa pneumonia remains a difficult therapeutic problem. Optimal doses and modes of administration of single agents often do not result in acceptable outcomes. Further, emergence of resistance occurs frequently in this setting with single-agent chemotherapy. The purpose of these experiments was to evaluate combination chemotherapy with meropenem plus tobramycin for P. aeruginosa in a murine pneumonia model. Neutropenia was induced by cyclophosphamide. Pharmacokinetics of meropenem and tobramycin were determined using a population pharmacokinetic approach. Both drugs were given at 4-h intervals. Meropenem was administered as total daily doses of 30 to 600 mg/kg of body weight, while tobramycin doses ranged from 50 to 400 mg/kg. Combination therapy evaluated all combinations of 50, 100, and 150 mg/kg/day of tobramycin doses with 60 or 300 mg/kg/day of meropenem. Total and drug-resistant organisms were enumerated. Meropenem alone had a near-maximal effect at 60 mg/kg/day (3.18 log10 [CFU/g] kill from stasis). The time > MIC in epithelial lining fluid (ELF) at this dose was 35.25% of 24 h. For tobramycin alone, the near-maximal effect was at 150 mg/kg/day and the area under the concentration-time curve over 24 h in the steady state divided by the MIC (AUC/MIC ratio) in ELF was 240.3. Resistance suppression occurred at an ELF AUC/MIC ratio of 110.6. For combination therapy, the near-maximal effect was reached at 60 mg/kg/day and 50 mg/kg/day of meropenem and tobramycin, which produced a 35.25% time > MIC in ELF and an ELF AUC/MIC ratio of 80.1. The interaction was additive. All combination regimens suppressed resistance. Combination therapy produced additive drug interaction and suppressed all resistance amplification. It is likely that optimal therapy for Pseudomonas aeruginosa pneumonia will involve a combination of agents.
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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.