ArticleAntimicrobial agents and chemotherapy2015
Antimicrobial Activity of Fosfomycin-Tobramycin Combination against Pseudomonas aeruginosa Isolates Assessed by Time-Kill Assays and Mutant Prevention Concentrations.
Article in Antimicrobial agents and chemotherapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 29 papers.
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Who cites it
29 citing papers in PubMed, 43 citations in OpenAlex.
- Nanostructured Lipid Microparticles as Tobramycin Carriers for Pulmonary Drug Delivery.Pharmaceutics · 2026Article
- Synergistic antibacterial activity and prevention of drug resistance of daptomycin combined with fosfomycin against methicillin-resistantAntimicrobial agents and chemotherapy · 2025Article
- Efficacy of Endolysin LysAB1245 Combined with Colistin as Adjunctive Therapy Against Colistin-Resistant Gram-Negative Bacteria.Antibiotics (Basel, Switzerland) · 2025Article
- Article
- Phenotypic and Molecular Analysis of Fosfomycin Resistance AmongInfection and drug resistance · 2025Article
- Navigating the Current Treatment Landscape of Metallo-β-Lactamase-Producing Gram-Negative Infections: What are the Limitations?Infectious diseases and therapy · 2024Review
- Halicin: A New Horizon in Antibacterial Therapy against Veterinary Pathogens.Antibiotics (Basel, Switzerland) · 2024Article
- Mechanisms of antibiotic resistance inBiofilm · 2023Article
- Efficacy of antibiotic combinations in an experimental sepsis model with Pseudomonas aeruginosa.Brazilian journal of microbiology : [publication of the Brazilian Society for Microbiology] · 2023Article
- Catalytic performance and antibacterial behaviour with molecular docking analysis of silver and polyacrylic acid doped graphene quantum dots.RSC advances · 2023Article
- Collateral Sensitivity to Fosfomycin of Tobramycin-Resistant Mutants ofInternational journal of molecular sciences · 2023Article
- Drug Combinations to Prevent Antimicrobial Resistance: Various Correlations and Laws, and Their Verifications, Thus Proposing Some Principles and a Preliminary Scheme.Antibiotics (Basel, Switzerland) · 2022Article
- The Emergence and Dissemination of Multidrug ResistantAntibiotics (Basel, Switzerland) · 2022Review
- Convergent phenotypic evolution towards fosfomycin collateral sensitivity of Pseudomonas aeruginosa antibiotic-resistant mutants.Microbial biotechnology · 2022Article
- Fosfomycin as Partner Drug for Systemic Infection Management. A Systematic Review of Its Synergistic Properties from In Vitro and In Vivo Studies.Antibiotics (Basel, Switzerland) · 2020Review
- In vitro evaluation of double carbapenem and colistin combinations against OXA-48, NDM carbapenemase-producing colistin-resistant Klebsiella pneumoniae strains.Antimicrobial resistance and infection control · 2020Article
- Tolerance and Persistence ofFrontiers in microbiology · 2020Review
- Synergistic Combination of Linezolid and Fosfomycin Closing Each Other's Mutant Selection Window to Prevent Enterococcal Resistance.Frontiers in microbiology · 2020Article
- New microbiological aspects of fosfomycin.Revista espanola de quimioterapia : publicacion oficial de la Sociedad Espanola de Quimioterapia · 2019Review
- Evaluation of the Bactericidal Activity of Fosfomycin in Combination with Selected Antimicrobial Comparison Agents Tested against Gram-Negative Bacterial Strains by Using Time-Kill Curves.Antimicrobial agents and chemotherapy · 2019Article
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Authors and funding
6 authors at 4 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The antibacterial activity of fosfomycin-tobramycin combination was studied by time-kill assay in eight Pseudomonas aeruginosa clinical isolates belonging to the fosfomycin wild-type population (MIC = 64 μg/ml) but with different tobramycin susceptibilities (MIC range, 1 to 64 μg/ml). The mutant prevention concentration (MPC) and mutant selection window (MSW) were determined in five of these strains (tobramycin MIC range, 1 to 64 μg/ml) in aerobic and anaerobic conditions simulating environments that are present in biofilm-mediated infections. Fosfomycin-tobramycin was synergistic and bactericidal for the isolates with mutations in the mexZ repressor gene, with a tobramycin MIC of 4 μg/ml. This effect was not observed in strains displaying tobramycin MICs of 1 to 2 μg/ml due to the strong bactericidal effect of tobramycin alone. Fosfomycin presented higher MPC values (range, 2,048 to >2,048 μg/ml) in aerobic and anaerobic conditions than did tobramycin (range, 16 to 256 μg/ml). Interestingly, the association rendered narrow or even null MSWs in the two conditions. However, for isolates with high-level tobramycin resistance that harbored aminoglycoside nucleotidyltransferases, time-kill assays showed no synergy, with wide MSWs in the two environments. glpT gene mutations responsible for fosfomycin resistance in P. aeruginosa were determined in fosfomycin-susceptible wild-type strains and mutant derivatives recovered from MPC studies. All mutant derivatives had changes in the GlpT amino acid sequence, which resulted in a truncated permease responsible for fosfomycin resistance. These results suggest that fosfomycin-tobramycin can be an alternative for infections due to P. aeruginosa since it has demonstrated synergistic and bactericidal activity in susceptible isolates and those with low-level tobramycin resistance. It also prevents the emergence of resistant mutants in either aerobic or anaerobic environments.
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