ArticleBMC microbiology2024
Synergistic effect of fosfomycin and colistin against KPC-producing Klebsiella pneumoniae: pharmacokinetics-pharmacodynamics combined with transcriptomic approach.
Article in BMC microbiology, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 3 papers.
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.
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Who cites it
3 citing papers in PubMed.
- Enhanced antibacterial activity of antimicrobial peptide-antibiotic combinations against multidrug-resistant bacteria.FEMS microbes · 2026Review
- Effective Management of Carbapenem-Resistant Enterobacterales Bloodstream Infection with Organ Dissemination in Prolonged Severe Agranulocytosis Patients with Hematological Malignancy Through Combination Therapies Including Eravacycline.Infectious diseases and therapy · 2025Article
- Overcoming the drug resistance barrier: progress in fosfomycin combination therapy against multidrug-resistant pathogens.Frontiers in microbiology · 2025Review
Corrections and comments
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Authors and funding
8 authors.
Funding
Abstract
objectivesThe aim of this study was to identify the synergistic effect and mechanisms of fosfomycin (FM) combined with colistin (COL) against KPC-producing Klebsiella pneumoniae (KPC-Kp).
methodsThe bactericidal effects, induced drug resistance and cytotoxicity of FM combined with COL were evaluated by time-kill assays and mutation rate test. Time-kill assays and transcriptomics analysis were used to further clarify the mechanism of FM combined with COL. The bacteria were taken from different points in time-kill assays, reactive oxygen species (ROS), nitric oxide and redox related enzymes were detected. The mechanism of synergistic bactericidal action was analyzed by transcriptome.
resultsThe bactericidal effect of FM combined with COL was better than that of monotherapy. The mutation frequency of FM alone at low dose (8 mg/L) was higher than that at high dose (64 mg/L). COL induced resistant isolates resulted in FM and COL resistance, while FM alone or combined with COL only resulted in FM resistance. The survival rate of Thp-1 cells in FM combined with COL against K. pneumoniae was higher than that of monotherapy. The intracellular nitric oxide, activities of total superoxide dismutase and catalase were increased along with the increase of FM concentration against KPC-Kp. FM combined with COL induced ROS accumulation and antioxidant capacity increase. Transcriptome analysis showed FM combined with COL could regulate the levels of soxRS and oxidative phosphorylation, in order to clear ROS and repair damage. In addition, FM combined with COL could result in synergetic bactericidal efficacy by inhibiting ribosomal transcription.
conclusionsFM combined with COL mediated synergistic bactericidal effect by regulating ROS accumulation and inhibiting ribosomal protein transcription, resulting in lower resistance and cytotoxicity.
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