Details

Autor(en) / Beteiligte

• Trebosc, Vincent
• Kemmer, Christian
• Lociuro, Sergio
• Gitzinger, Marc
• Dale, Glenn E.

Titel

Rifabutin for infusion (BV100) for the treatment of severe carbapenem-resistant Acinetobacter baumannii infections

Ist Teil von

• Drug discovery today, 2021-09, Vol.26 (9), p.2099-2104

Ort / Verlag

England: Elsevier Ltd

Erscheinungsjahr

2021

Quelle

MEDLINE

Beschreibungen/Notizen

• •A unexpected activity of rifabutin (RBT) towards A. baumanni has been discovered.•RBT displays a potent activity towards A. baumannii in iron depleted environments.•RBT is specifically transported into A. baumannii via the siderophore receptor FhuE.•BV100 (rifabutin for infusion) has an unprecedented in vivo activity towards CRAB.•BV100 addresses the low oral bioavailability and wide interpatient variability of RBT. Rifamycin antibiotics were discovered during the 1950s, and their main representative, rifampicin, remains a cornerstone treatment for TB. The clinical use of rifamycin is restricted to mycobacteria and Gram-positive infections because of its poor ability to penetrate the Gram-negative outer membrane. Rifabutin, a rifamycin antibiotic approved for the prevention of Mycobacterium avium complex disease, makes an exception to this rule by hijacking the iron uptake system of Acinetobacter baumannii, resulting in potent activity against this important Gram-negative pathogen. Here, we describe recent findings on the specific activity of rifabutin and provide evidence of the need for the development of an intravenous formulation of rifabutin (BV100) for the treatment of difficult-to-treat carbapenem-resistant A.baumannii infections.