Anti-Mutant Efficacy of Combination Therapy with Doripenem and Levofloxacin: In Vitro Model Studies with Pseudomonas Aeruginosa
Abstract
Relevance. The tendency to a decrease in sensitivity of bacterial agents to old antibiotics, as well as the slowdown in creation of new medications, dictate the need to develop effective approaches to combat bacterial resistance. Aim. Evaluation of the applicability of a pharmacokinetically-based approach to predicting anti-mutant effectiveness of combined therapy with doripenem and levofloxacin against gram-negative bacteria Pseudomonas aeruginosa. Material and methods. A collection strain of Pseudomonas aeruginosa was used in the study. The values of MPC (mutant prevention concentration) of the combination of doripenem and levofloxacin were evaluated at a ratio of their concentrations equal to therapeutic ratios of the area under the pharmacokinetic curve in the in vitro dynamic model. 5-day treatments with clinical doses of doripenem and levofloxacin individually and in combination were simulated. Bacteria-containing medium was sampled during the experiments and plated on agar media containing 2MIC of each antibiotic. Results. The MPCs of doripenem and levofloxacin decreased 4 times when used in combination compared to MPC values when used separately. P.aeruginosa population was enriched with resistant mutants during monotherapy with each medication; the number of the bacteria did not decrease or even increased by the end of observation period. The use of doripenem/levofloxacin combination completely prevented development of resistance to both drugs in P.aeruginosa. The…
Read the paper
Related studies
- Severe clinical outcomes of COVID-19 associated with proton pump inhibitors: a nationwide cohort study with propensity score matching
- Thiophenes—Naturally Occurring Plant Metabolites: Biological Activities and In Silico Evaluation of Their Potential as Cathepsin D Inhibitors
- Inhalable Mannosylated Rifampicin–Curcumin Co-Loaded Nanomicelles with Enhanced In Vitro Antimicrobial Efficacy for an Optimized Pulmonary Tuberculosis Therapy
- Association between cord blood 25-hydroxyvitamin D concentrations and respiratory tract infections in the first 6 months of age in a Korean population: a birth cohort study (COCOA)
- GC-MS Analysis and Biomedical Therapy of Oil from n-Hexane Fraction of Scutellaria edelbergii Rech. f.: In Vitro, In Vivo, and In Silico Approach
- Novel Pharmacokinetic/Pharmacodynamic Parameters Quantify the Exposure–Effect Relationship of Levofloxacin against Fluoroquinolone-Resistant Escherichia coli
Go deeper in Evidence Hub
Evidence Hub adds a study data sheet (design, sample size, evidence level, key numbers), an AI summary and a chat grounded in the paper's text.