The Combination of Fosfomycin, Metronidazole, and Recombinant Human Granulocyte-Macrophage Colony-Stimulating Factor is Stable in vitro and Has Maintained Antibacterial Activity.

BACKGROUND: Treatment of secondary peritonitis includes surgery and antimicrobial agents. Antimicrobial agents are often administered intravenously, however, the alternative route intraperitoneal administration could be considered. Investigations must be conducted prior to clinical application. Therefore, we aimed to investigate the combination of fosfomycin, metronidazole, and recombinant human granulocyte-macrophage colony-stimulating factor with regard to its chemical properties and the solution's stability. In addition, the antibacterial effect of the mixed drug solution was compared with the effect of the individual antibacterial agents.

METHODS: The drugs were mixed to an aqueous solution. Basic chemical investigations of pH, precipitation, and calculated osmolarity of the drug combination were conducted. Fosfomycin and metronidazole's chemical stability was investigated using High Pressure Liquid Chromatography-Mass Spectrometry. Microbiological investigations using the agar cup method were carried out to measure the antibacterial effect of fosfomycin and metronidazole.

RESULTS: The aqueous solution of the combination of the three drugs had a pH of 7.46-7.62, which was stable during 24 h, was without precipitation, and had a calculated osmolarity of 293 mOsm/l. High Pressure Liquid Chromatography-Mass Spectrometry found stable concentrations of fosfomycin and metronidazole both alone and in combination during 24 h. The antibacterial effect of the drug combination solution was similar to the antibacterial effects of fosfomycin and metronidazole alone.

CONCLUSION: The drug combination had neutral and stable pH, was iso-osmotic, and had stable concentrations during 24 h of storage. The antibacterial effect of fosfomycin and metronidazole were not altered when the drugs were mixed.