Rifabutin treatment methods, uses, and compositions

Inventors

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

Assignees

Bioversys AG

Abstract

The invention provides systems and methods for increased clinical efficacy of rifabutin against A. baumannii. The invention takes advantage of the discovery of a ferric-coprogen (FhuE) receptor that is responsible for the uptake of rifabutin into A. baumannii cells. Methods preferably include obtaining a sample from a patient suspected of having an infection; performing a test on the sample to identify an infection of A. baumannii in the patient; and providing a formulation of rifabutin for treating the patient that, when administered to the patient, maximizes a resultant AUC and/or Cmax. The method may include administering the formulation of rifabutin to the patient. Preferably the formulation is delivered to the patient, e.g., by intravenous injection and results in a Cmax is that greater than about 2 mg/L and optionally less than about 50 mg/L.

Core Innovation

The invention relates to systems and methods for treating Acinetobacter baumannii infection using rifabutin. The approach enables rifabutin uptake by activating a ferric-coprogen (FhuE) TonB-dependent siderophore receptor through the bacterial TonB box, so that rifabutin can be taken up in the presence of the FhuE receptor.

The described work links rifabutin efficacy to high systemic exposure achieved by administering rifabutin as an intravenous liquid formulation. The document states that clinical efficacy requires sufficient systemic rifabutin exposure, expressed using Cmax and AUC constraints, and that such exposure is typically achievable via intravenous formulations.

For formulation, the invention provides liquid intravenous compositions containing rifabutin in an aqueous system with a selected polar solvent and an acid to promote dissolution. The document describes rifabutin formulations as aqueous solutions with a pH within a specified range and includes enumerated solvent selections and acid selections, including acetic acid.

Claims Coverage

The independent claims cover two aspects: a method of treating A. baumannii infection by administering an aqueous rifabutin composition to a patient, and a composition for use in treating A. baumannii infection defined by rifabutin, water, a solvent, and a pH range. Across the independent claims and their dependents, the claims include multiple inventive features: aqueous rifabutin composition definition, pH constraint, solvent definition, acid inclusion/selection, pharmacokinetic constraints using Cmax and AUC, and intravenous administration.

Overall, the claim set focuses on treating A. baumannii infection using an aqueous rifabutin composition defined by rifabutin, water, a solvent, and a pH from about 3.0 to about 7.0, optionally including an added acid with enumerated selections including acetic acid. Additional claim refinements tie the treatment to intravenous administration and to systemic rifabutin exposure constraints expressed as Cmax and AUC ranges.

Stated Advantages

Documented Applications