ArticleThe Journal of antimicrobial chemotherapy2020
In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms.
Article in The Journal of antimicrobial chemotherapy, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers, 2 of them syntheses that pooled it.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
22 citing papers in PubMed, 2 syntheses or guidelines pooled it.
- Drug-resistantClinical microbiology reviews · 2025Pooled it
- In search for a synergistic combination against pandrug-resistant A. baumannii; methodological considerations.Infection · 2022Pooled it
- BV100 (rifabutin IV) drug interaction studies in healthy subjects with index CYP450 3A probes midazolam and itraconazole.The Journal of antimicrobial chemotherapy · 2026Article
- Rifabutin Loaded Biogenic Silver Nanoparticles: Development, Characterization, and Evaluation of Antidiabetic Activity in Streptozotocin Induced Diabetic Rats.Chemistry & biodiversity · 2026Article
- The Correlation between Binding and Transport of a Siderophore Complex through Its TonB-Dependent Transporter.ACS omega · 2026Article
- Single-ascending and multiple-ascending dose study of the pharmacokinetics, safety, and tolerability of BV100 (rifabutin for infusion) in healthy volunteers.Antimicrobial agents and chemotherapy · 2026Article
- Design, Synthesis, and Antibacterial Evaluation of Rifampicin-Siderophore Conjugates.ACS infectious diseases · 2025Article
- The global resistance problem and the clinical antibacterial pipeline.Nature reviews. Microbiology · 2025Review
- Review
- Combinations of Antibiotics Effective against Extensively- and Pandrug-ResistantMicroorganisms · 2024Article
- Treatment Strategies of Colistin ResistanceAntibiotics (Basel, Switzerland) · 2024Review
- Genome-wide screen reveals cellular functions that counteract rifampicin lethality inMicrobiology spectrum · 2024Article
- Article
- A Novel Natural Siderophore Antibiotic Conjugate Reveals a Chemical Approach to Macromolecule Coupling.ACS central science · 2023Article
- Article
- On the Hunt for Next-Generation Antimicrobial Agents: An Online Symposium Organized Jointly by the French Society for Medicinal Chemistry (Société de Chimie Thérapeutique) and the French Microbiology Society (Société Française de Microbiologie) on 9-10 December 2021.Pharmaceuticals (Basel, Switzerland) · 2022Article
- Article
- Cefiderocol for the Treatment of Multidrug-Resistant Gram-Negative Bacteria: A Systematic Review of Currently Available Evidence.Frontiers in pharmacology · 2022Review
- JMM Profile: Carbapenems: a broad-spectrum antibiotic.Journal of medical microbiology · 2021Review
- Systematic Review of Antimicrobial Combination Options for Pandrug-ResistantAntibiotics (Basel, Switzerland) · 2021Review
Corrections and comments
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Authors and funding
11 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
backgroundRifabutin, an oral drug approved to treat Mycobacterium avium infections, demonstrated potent activity against Acinetobacter baumannii in nutrient-limited medium enabled by rifabutin cellular uptake through the siderophore receptor FhuE.
objectivesTo determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates.
methodsTwo hundred and ninety-three carbapenem-resistant A. baumannii clinical isolates collected from Europe, the USA and Asia during 2017-19 were used for MIC determination. Sequencing/genotyping of fhuE, rpoB and arr-2 genes in isolates with elevated rifabutin MIC combined with genetic engineering and gene expression quantification was used to characterize rifabutin's mode of action and resistance mechanisms.
resultsRifabutin showed excellent activity on the strain panel, with an MIC50/90 of 0.008/1 mg/L, and was superior to all other antibiotics tested, including colistin, tigecycline and cefiderocol (MIC90 of 8 mg/L). Rifabutin remained active on resistant subpopulations, including strains resistant to the siderophore-drug conjugate cefiderocol (MIC90 of 2 mg/L, n = 23). At least two independent resistance mechanisms were required to abolish rifabutin activity, which is in line with the dose-dependent mutational resistance frequency reaching 10-9 at rifabutin concentrations at or above 2 mg/L.
conclusionsThis study demonstrated the potent activity of rifabutin against carbapenem-resistant A. baumannii. We propose that FhuE-mediated active uptake of rifabutin enables activity against rifampicin-resistant isolates. To achieve clinically meaningful strain coverage and to avoid rapid resistance development, rifabutin concentrations ≥2 mg/L are required, something rifabutin oral formulations cannot deliver.
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