[Bacterial combination effect between carumonam and eight other antibiotics]

Area of Science:

• Microbiology
• Pharmacology
• Infectious Diseases

Background:

• Antibiotic resistance is a growing concern, necessitating the exploration of novel combination therapies.
• Carumonam (CRMN) is a monobactam antibiotic with activity against Gram-negative bacteria.

Purpose of the Study:

• To evaluate the in vitro and in vivo interactions between carumonam (CRMN) and eight other antibiotics against key Gram-negative pathogens.
• To determine the potential for synergistic, additive, or antagonistic effects in antibiotic combinations.

Main Methods:

• Agar dilution checkerboard technique was employed to assess in vitro interactions against 88 clinical isolates (E. coli, P. vulgaris, S. marcescens, P. aeruginosa).
• Phase-contrast microscopy and an in vivo mouse model of urinary tract infection were used to confirm synergistic effects observed in vitro.

Main Results:

• Most CRMN combinations exhibited additive or indifferent interactions.
• Synergistic effects were observed with CRMN plus fosfomycin, gentamicin (GM), or dibekacin against S. marcescens and P. aeruginosa.
• No antagonistic interactions were detected between CRMN and any of the tested antibiotics.
• In vivo studies confirmed the synergistic activity of CRMN plus GM against P. aeruginosa in a murine UTI model.

Conclusions:

• Carumonam (CRMN) combinations with other antibiotics generally do not result in antagonism.
• The observed synergistic effects, particularly with fosfomycin and aminoglycosides, suggest potential utility in treating Gram-negative infections.
• CRMN combination therapy may be a viable option for initial treatment of infections caused by susceptible pathogens.