ArticleAntimicrobial agents and chemotherapy2012
Fosfomycin enhances the active transport of tobramycin in Pseudomonas aeruginosa.
Article in Antimicrobial agents and chemotherapy, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 21 papers.
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Who cites it
21 citing papers in PubMed, 42 citations in OpenAlex.
- Comparing inhaled colistin with inhaled fosfomycin/tobramycin as an adjunctive treatment for ventilator-associated pneumonia: An open-label randomized controlled trial.The clinical respiratory journal · 2023Trial
- In Vitro Antibacterial Activities of Fosfomycin againstAnimals : an open access journal from MDPI · 2024Article
- Efficacy of antibiotic combinations in an experimental sepsis model with Pseudomonas aeruginosa.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Semi-mechanistic PK/PD modelling of fosfomycin and sulbactam combination against carbapenem-resistantAntimicrobial agents and chemotherapy · 2023Article
- Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants.Microbial biotechnology · 2022Article
- Dynamic Adaptive Response ofAntibiotics (Basel, Switzerland) · 2021Article
- Validation of Qualitative Broth Volatilization Checkerboard Method for Testing of Essential Oils: Dual-Column GC-FID/MS Analysis and In Vitro Combinatory Antimicrobial Effect ofPlants (Basel, Switzerland) · 2021Article
- Cefiderocol Retains Antibiofilm Activity in Multidrug-Resistant Gram-Negative Pathogens.Antimicrobial agents and chemotherapy · 2021Article
- Article
- Itaconic Acid Increases the Efficacy of Tobramycin againstPharmaceutics · 2020Article
- In Vitro Activity of Fosfomycin in Double and Triple Combinations with Imipenem, Ciprofloxacin and Tobramycin Against Multidrug-Resistant Escherichia coli.Current microbiology · 2020Article
- Use of Calgary and Microfluidic BioFlux Systems To Test the Activity of Fosfomycin and Tobramycin Alone and in Combination against Cystic Fibrosis Pseudomonas aeruginosa Biofilms.Antimicrobial agents and chemotherapy · 2018Article
- Pharmacodynamics of Aerosolized Fosfomycin and Amikacin against Resistant Clinical Isolates of Pseudomonas aeruginosa and Klebsiella pneumoniae in a Hollow-Fiber Infection Model: Experimental Basis for Combination Therapy.Antimicrobial agents and chemotherapy · 2017Article
- Fosfomycin.Clinical microbiology reviews · 2016Review
- Antimicrobial Activity of Fosfomycin-Tobramycin Combination against Pseudomonas aeruginosa Isolates Assessed by Time-Kill Assays and Mutant Prevention Concentrations.Antimicrobial agents and chemotherapy · 2015Article
- Unexpected challenges in treating multidrug-resistant Gram-negative bacteria: resistance to ceftazidime-avibactam in archived isolates of Pseudomonas aeruginosa.Antimicrobial agents and chemotherapy · 2015Article
- Potentiation effects of amikacin and fosfomycin against selected amikacin-nonsusceptible Gram-negative respiratory tract pathogens.Antimicrobial agents and chemotherapy · 2014Article
- Fosfomycin and tobramycin in combination downregulate nitrate reductase genes narG and narH, resulting in increased activity against Pseudomonas aeruginosa under anaerobic conditions.Antimicrobial agents and chemotherapy · 2013Article
- Eradication of Pseudomonas aeruginosa biofilms on cultured airway cells by a fosfomycin/tobramycin antibiotic combination.Pathogens and disease · 2013Article
- Article
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Authors and funding
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Elevated levels of mucins present in bronchiectatic airways predispose patients to bacterial infections and reduce the effectiveness of antibiotic therapies by directly inactivating antibiotics. Consequently, new antibiotics that are not inhibited by mucins are needed to treat chronic respiratory infections caused by Pseudomonas aeruginosa and Staphylococcus aureus. In these studies, we demonstrate that fosfomycin synergistically enhances the activity of tobramycin in the presence of mucin. The bactericidal killing of a novel 4:1 (wt/wt) combination of fosfomycin-tobramycin (FTI) is superior (>9 log(10) CFU/ml) relative to its individual components fosfomycin and tobramycin. Additionally, FTI has a mutation frequency resulting in an antibiotic resistance >3 log(10) lower than for fosfomycin and 4 log(10) lower than for tobramycin for P. aeruginosa. Mechanistic studies revealed that chemical adducts are not formed, suggesting that the beneficial effects of the combination are not due to molecular modification of the components. FTI displayed time-kill kinetics similar to tobramycin and killed in a concentration-dependent fashion. The bactericidal effect resulted from inhibition of protein biosynthesis rather than cell wall biosynthesis. Studies using radiolabeled antibiotics demonstrated that tobramycin uptake was energy dependent and that fosfomycin enhanced the uptake of tobramycin in P. aeruginosa in a dose-dependent manner. Lastly, mutants resistant to fosfomycin and tobramycin were auxotrophic for specific carbohydrates and amino acids, suggesting that the resistance arises from mutations in specific active transport mechanisms. Overall, these data demonstrate that fosfomycin enhances the uptake of tobramycin, resulting in increased inhibition of protein synthesis and ultimately bacterial killing.
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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.