Drug intelligence / Profile preview

fosfomycin + ofloxacin + rifampicin

Development stage
Preclinical
Lead developer
Merck
Modality
Small Molecules
Administration
Intravenous, Oral
01

Overview

This is a combination antibiotic therapy consisting of three agents—fosfomycin, ofloxacin, and rifampicin. Each component has a distinct mechanism of action: - **Fosfomycin** is a broad-spectrum bactericidal antibiotic that inhibits bacterial cell wall synthesis by inactivating the enzyme UDP-N-acetylglucosamine enolpyruvyl transferase (MurA), which catalyzes an early step in peptidoglycan biosynthesis[3][5]. - **Ofloxacin** is a fluoroquinolone antibiotic that inhibits bacterial DNA gyrase and topoisomerase IV, enzymes essential for DNA replication, transcription, repair, and recombination. - **Rifampicin** (also known as rifampin) inhibits bacterial DNA-dependent RNA polymerase, thereby suppressing RNA synthesis. The combination aims to provide broad-spectrum coverage against both Gram-positive and Gram-negative bacteria. Fosfomycin and rifampicin have demonstrated synergistic activity against biofilm-forming bacteria such as methicillin-resistant Staphylococcus aureus (MRSA), particularly in implant-associated infections[1][4]. Ofloxacin adds further activity against various pathogens due to its fluoroquinolone class properties. This triple combination may be considered for difficult-to-treat or device-related infections where biofilm formation is suspected or confirmed.

02

Targets

MurA (UDP-N-acetylglucosamine 1-carboxyvinyltransferase)rpoB (DNA-directed RNA polymerase subunit beta)Topo IV (Bacterial Topoisomerase IV)DNA gyrase

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