Fonnes Siv, Holzknecht Barbara Juliane, Gasbjerg Lærke Smidt, Weisser Johan Juhl, Hallberg Hanne Wiese, Arpi Magnus, Rosenberg Jacob
Centre for Perioperative Optimisation, Department of Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark.
Drug Res (Stuttg). 2018 Jun;68(6):349-354. doi: 10.1055/s-0043-123933. Epub 2017 Dec 19.
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.
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.
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.
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.
继发性腹膜炎的治疗包括手术和抗菌药物。抗菌药物通常通过静脉给药，然而，也可以考虑腹腔内给药这一替代途径。在临床应用前必须进行研究。因此，我们旨在研究磷霉素、甲硝唑和重组人粒细胞巨噬细胞集落刺激因子组合的化学性质和溶液稳定性。此外，将混合药物溶液的抗菌效果与单独抗菌药物的效果进行比较。
将药物混合制成水溶液。对药物组合的pH值、沉淀和计算渗透压进行基础化学研究。使用高压液相色谱 - 质谱法研究磷霉素和甲硝唑的化学稳定性。采用琼脂杯法进行微生物学研究，以测定磷霉素和甲硝唑的抗菌效果。
三种药物组合的水溶液pH值为7.46 - 7.62，在24小时内稳定，无沉淀，计算渗透压为293 mOsm/l。高压液相色谱 - 质谱法发现磷霉素和甲硝唑单独及组合时在24小时内浓度稳定。药物组合溶液的抗菌效果与磷霉素和甲硝唑单独的抗菌效果相似。
药物组合具有中性且稳定的pH值，等渗，在储存24小时内浓度稳定。混合药物时，磷霉素和甲硝唑的抗菌效果未改变。
