دورية أكاديمية
أعرض في EDS

In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms.

التفاصيل البيبلوغرافية
العنوان: In vitro activity of rifabutin against 293 contemporary carbapenem-resistant Acinetobacter baumannii clinical isolates and characterization of rifabutin mode of action and resistance mechanisms.
المؤلفون: Trebosc V; BioVersys AG, Basel, Switzerland., Schellhorn B; BioVersys AG, Basel, Switzerland., Schill J; BioVersys AG, Basel, Switzerland., Lucchini V; BioVersys AG, Basel, Switzerland.; Biozentrum, University of Basel, Basel, Switzerland., Bühler J; BioVersys AG, Basel, Switzerland., Bourotte M; BioVersys SAS, Lille, France., Butcher JJ; BioVersys AG, Basel, Switzerland., Gitzinger M; BioVersys AG, Basel, Switzerland., Lociuro S; BioVersys AG, Basel, Switzerland., Kemmer C; BioVersys AG, Basel, Switzerland., Dale GE; BioVersys AG, Basel, Switzerland.
المصدر: The Journal of antimicrobial chemotherapy [J Antimicrob Chemother] 2020 Dec 01; Vol. 75 (12), pp. 3552-3562.
نوع المنشور: Journal Article; Research Support, Non-U.S. Gov't
اللغة: English
بيانات الدورية: Publisher: Oxford University Press Country of Publication: England NLM ID: 7513617 Publication Model: Print Cited Medium: Internet ISSN: 1460-2091 (Electronic) Linking ISSN: 03057453 NLM ISO Abbreviation: J Antimicrob Chemother Subsets: MEDLINE
أسماء مطبوعة: Publication: 1997- : London : Oxford University Press
Original Publication: London, New York, Academic Press.
مواضيع طبية MeSH: Acinetobacter baumannii*/genetics, Anti-Bacterial Agents/pharmacology ; Asia ; Carbapenems/pharmacology ; Drug Resistance, Multiple, Bacterial ; Europe ; Microbial Sensitivity Tests ; Rifabutin/pharmacology
مستخلص: Background: Rifabutin, 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.
Objectives: To determine rifabutin in vitro activity and resistance mechanisms in a large panel of A. baumannii isolates.
Methods: Two 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.
Results: Rifabutin 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.
Conclusions: This 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.
(© The Author(s) 2020. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy.)
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المشرفين على المادة: 0 (Anti-Bacterial Agents)
0 (Carbapenems)
1W306TDA6S (Rifabutin)
تواريخ الأحداث: Date Created: 20200902 Date Completed: 20210624 Latest Revision: 20210624
رمز التحديث: 20231215
مُعرف محوري في PubMed: PMC7662187
DOI: 10.1093/jac/dkaa370
PMID: 32869081
قاعدة البيانات: MEDLINE
الوصف
تدمد:1460-2091
DOI:10.1093/jac/dkaa370