Antibiotic combination therapies
Inventors
Trebosc, Vincent • Kemmer, Christian • Dale, Glenn E. • Lociuro, Sergio • Gitzinger, Marc
Assignees
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Publication Number
US-12370184-B2
Publication Date
2025-07-29
Expiration Date
Abstract
The invention provides antibiotic combination therapies for treating an A. baumannii infection in a subject. The combination therapies include rifabutin and a second antibiotic, such as colistin and cefiderocol.
Core Innovation
Rifabutin-based combination therapies are described for treating Acinetobacter baumannii infections in a subject. The therapy provides rifabutin together with a second antibiotic selected from a group consisting of a polymyxin, a cationic antimicrobial peptide, and a cephalosporin.
The described findings address the problem of treating A. baumannii infections where rifamycin activity and/or activity of conventional partners can be limited by resistance. The document reports unexpected synergistic effects when rifabutin is combined with polymyxins, including colistin, or with cephalosporins such as cefiderocol.
Rifabutin plus colistin and rifabutin plus cefiderocol show synergy across diverse MDR/XDR A. baumannii clinical isolates, including isolates that are resistant to rifabutin and/or to the second antibiotic. The synergy is also reported in isolates associated with elevated MICs linked to rpoB mutations, and the combination is contrasted with rifampicin/colistin behavior.
Claims Coverage
The partial content includes two independent claims that share the same core structure: rifabutin combined with a second antibiotic selected from specified classes to treat an A. baumannii infection in a subject. The independent claims distinguish between a method of providing rifabutin with the selected second antibiotic and a combination therapy in a therapeutically effective amount, and both cover multiple second-antibiotic classes as the main inventive feature set.
Rifabutin with a selected second antibiotic to treat A. baumannii infection
A method of treating an A. baumannii infection in a subject comprising providing to a subject infected with A. baumannii rifabutin and a second antibiotic selected from the group consisting of a polymyxin, a cationic antimicrobial peptide, and a cephalosporin.
Therapeutically effective rifabutin and second antibiotic combination therapy for A. baumannii
A combination therapy comprising rifabutin and a second antibiotic selected from the group consisting of a polymyxin, a cationic antimicrobial peptide, and cephalosporin, wherein the combination therapy comprises rifabutin and the second antibiotic in a therapeutically effective amount to treat an A. baumannii infection in a subject.
Across both independent claims, the coverage centers on co-provision of rifabutin with a second antibiotic chosen from polymyxin, a cationic antimicrobial peptide, and a cephalosporin class to treat an A. baumannii infection in a subject, with one claim framed as a method of providing and the other framed as a therapeutically effective combination therapy.
Stated Advantages
Unexpected synergistic effects when rifabutin is combined with a polymyxin, including colistin, or with cefiderocol.
Synergy is reported across diverse MDR/XDR A. baumannii clinical isolates, including isolates resistant to rifabutin and/or the second antibiotic.
Rifabutin/colistin is reported to overcome resistance even when elevated MICs are associated with rpoB mutations.
Combination therapy is supported by synergy assessment using checkerboard/FICI and includes reported MIC fold-decreases and synergy criteria.
Documented Applications
Treatment of an Acinetobacter baumannii infection in a subject using a rifabutin-based combination therapy with a second antibiotic selected from polymyxin, a cationic antimicrobial peptide, and cephalosporin.
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