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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: BACKGROUND, METHODS, RESULTS. Meshes: Animals, Anti-Bacterial Agents, Disease Models, Animal, Drug Synergism, Drug Therapy, Combination, Female, Levofloxacin, Meropenem, Mice, Microbial Sensitivity Tests, Pneumonia, Pseudomonas Infections, Pseudomonas aeruginosa, Thienamycins.
user
Is combination treatment with meropenem plus levofloxacin synergistic against Pseudomonas aeruginosa infection in a murine model of pneumonia? Context: Meropenem 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. A 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. Meropenem 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.
assistant
The 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. Final Decision: yes