ArticleThe Journal of antimicrobial chemotherapy2024
Comparative in vitro efficacy of antibiotics against the intracellular reservoir of Staphylococcus aureus.
Article in The Journal of antimicrobial chemotherapy, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
4 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Genome-Scale Meta-analysis of Host Responses to Staphylococcus aureus Identifies Pathways for Host-Directed Therapeutic Targeting.The Journal of infectious diseases · 2025Pooled it
- Design of a cyclic peptide targeting intracellular Staphylococcus aureus.Molecular biomedicine · 2026Article
- Effect of antibiotics on Kupffer cell immunometabolism relative to intracellular killing ofmBio · 2025Article
- ORItavancin as a therapeutic regimen for Cardiac Implantable Electronic Devices infections with multidrug-resistant Gram-positive cocci (ORI-4-CIEDi) pilot study: rationale and design.Cardiology journal · 2025Article
Corrections and comments
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Authors and funding
3 authors.
Funding
Abstract
Staphylococcus aureus (SA) is a leading cause of bloodstream infection. The liver represents the sentinel immune organ for clearance of bloodstream pathogens and eradication of intracellular SA from liver-resident macrophages (Kupffer cells, KCs) eliminates the likely pathogenic reservoir that contributes to persistent bacteraemia.
objectivesWe assessed antimicrobial activity at phagolysosome-mimicking pH, intracellular penetration, and SA eradication within KCs in vitro for clinically prescribed antistaphylococcal agents alone or in combination: vancomycin, daptomycin, ceftaroline, ceftobiprole, oritavancin, oxacillin, cefazolin; rifampin and fosfomycin.
methodspH-adjusted broth microdilution assays, intracellular bioaccumulation assays, and intracellular killing assays against clinical bloodstream isolates were performed using a murine KC line with study agents.
resultsRifampin and β-lactams exhibited enhanced activity [2- to 16-fold minimum inhibitory concentrations (MIC) decrease] at phagolysosomal pH while vancomycin, oritavancin, daptomycin and fosfomycin demonstrated reduced activity (2- to 32-fold MIC increase in order of least to greatest potency reduction). All agents evaluated had poor to modest intracellular to extracellular concentration ratios (0.024-7.8), with exceptions of rifampin and oritavancin (intracellular to extracellular ratios of 17.4 and 78.2, respectively). Finally, we showed that the first-line treatment for SA bacteraemia (SAB), vancomycin, performed worse than all other tested antibiotics in eradicating intracellular SA at human Cmax concentration (0.20 log cfu decrease), while oritavancin performed better than all other agents alone (2.05 versus 1.06-1.36 log cfu decrease).
conclusionsOur findings raise concerns about the efficacy of commonly prescribed antibiotics against intracellular SA reservoirs and emphasize the need to consider targeting pathogen eradication from the liver to achieve early control of SAB.
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