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Drug Res (Stuttg) 2018; 68(06): 349-354
DOI: 10.1055/s-0043-123933
Original Article
© Georg Thieme Verlag KG Stuttgart · New York

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

Siv Fonnes
1   Centre for Perioperative Optimisation, Department of Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Barbara Juliane Holzknecht
2   Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Lærke Smidt Gasbjerg
3   Novo Nordisk Foundation Center for Basic Metabolic Research and Department of Biomedical Sciences, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen N, Denmark
4   Center for Diabetes Research, Herlev and Gentofte Hospital, University of Copenhagen, Hellerup, Denmark
,
Johan Juhl Weisser
5   Department of Pharmacy, Faculty of Health and Medical Sciences, University of Copenhagen, Copenhagen Ø, Denmark
,
Hanne Wiese Hallberg
2   Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Magnus Arpi
2   Department of Clinical Microbiology, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
,
Jacob Rosenberg
1   Centre for Perioperative Optimisation, Department of Surgery, Herlev and Gentofte Hospital, University of Copenhagen, Herlev, Denmark
› Author Affiliations
Further Information

Publication History

received 13 September 2017

accepted 28 November 2017

Publication Date:
19 December 2017 (online)

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Abstract

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.

Key words

Antibacterial drugs - inflammation - chemistry
 

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