HMH-CDI: Oral Triple Therapy for Mycobacterium abscessus
- Ray Sullivan
- Apr 12
- 1 min read
Researchers at the Center for Discovery & Innovation, Nutley, NJ, investigated a novel oral drug combination of tebipenem-avibactam, moxifloxacin, and rifabutin to combat Mycobacterium abscessus lung disease, which currently lacks effective treatments. Their study demonstrated that the triple combination exhibited strong bactericidal activity against both replicating and drug-tolerant forms of the bacteria in laboratory settings and in a mouse model. The enhanced killing effect appeared to stem from the drugs retaining their individual lethal mechanisms and suppressing bacterial resistance development. The novel three-drug oral combination presents several potential advantages compared to existing treatments for M. abscessus.
· Tebipenem is a β-lactam and avibactam is a β-lactamase inhibitor; together they inhibit cell wall synthesis.
· Moxifloxacin, a fluoroquinolone, inhibits DNA replication and repair.
· Rifabutin, a rifamycin, inhibits RNA polymerase, suppressing transcription.
Current treatments rely on underperforming drug combinations that often include parenteral, poorly tolerated, and bacteriostatic antibiotics, leading to unacceptably low cure rates (around 35% for strains with inducible macrolide resistance) and serious adverse events. Notably, there is no FDA-approved antibiotic specifically for this disease. Importantly, the research also explored the negative impact of bacteriostatic drugs on this bactericidal combination, highlighting the complexity of designing effective regimens. This work identifies a promising drug combination prototype and a preclinical evaluation framework for future optimization.
Sarathy JP, Xie M, Wong CF, Negatu DA, Rodriguez S, Zimmerman MD, Jimenez DC, Alshiraihi IM, Gonzalez-Juarrero M, Dartois V, Dick T. Toward a Bactericidal Oral Drug Combination for the Treatment of Mycobacterium abscessus Lung Disease. ACS Infect Dis. 2025 Apr 11;11(4):929-939. doi: 10.1021/acsinfecdis.4c00948. Epub 2025 Apr 1. PMID: 40168319.
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