Combating C. difficile resistance development with novel combinations of antimicrobials

Ed Siegwart explains how serial passage is being used to assess the resistance development of C. difficile to new drug combinations

13 Feb 2017
Lucy Vass
Administrator / Office Personnel

Editorial article

Ed Siegwart describes how the Microbiology Department tests clients’ novel antimicrobial compounds

In an interview with SelectScience®, Ed Siegwart, Senior Scientist in the Microbiology Department at Drug Development Services, LGC, explained how serial-passage testing was being used in the department. He described one of the team’s recent projects, assessing potential resistance of Clostridium difficile to miconazole-nisin, a novel combination antimicrobial developed by e-Theraputics.

The main benefit of serial passage is that you end up with a resistant mutant at the end, and that’s very useful for further testing

Ed Siegwart  Senior Scientist, LGC Microbiology: Anti-infectives

C.difficile is a leading cause of hospital-acquired diarrhea and can also lead to complications such as pseudomembranous colitis and sepsis. It is particularly a problem in elderly patients and patients who have recently received antibiotics. C. difficile is being targeted by researchers and manufacturers as there is increasing emergence of antimicrobial resistant strains, especially in hospital wards.

The Microbiology Department at LGC Drug Development Services tests clients’ novel antimicrobial compounds and investigates their potential against panels of bacterial isolates in a series of tests such as minimum inhibitory concentration (MIC), time-kill analysis and resistance development analysis. Serial passage is one of the methods used to assess the potential for a pathogen to develop resistance to compound.

Ed described how in this serial passage study, C. difficile was tested against miconazole-nisin in a doubling dilution concentration range. After incubation, a bacterial sample was taken from the concentration below the minimum inhibitory concentration and used to culture another miconazole-nisin concentration range. This was repeated multiple times over a number of days. “Against most compounds, most bacteria will develop resistance over the course of the serial passage,” Ed noted. However, in the case of miconazole-nisin, the MIC stayed constant, indicating that resistance did not develop over the course of the 14-day passage.

Ed concluded his presentation by explaining that bacteria are much less likely to develop resistance to combinations of molecules such as miconazole-nisin. This is because two separate mutations are often required within the same bacterium to confer resistance to the combination, making them a good option for pathogens such as C. difficile.

Watch Ed Siegwart’s poster presentation and visit LGC’s company profile to find out more about its services.
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MicrobiologyMicrobiology is the study of microorganisms including protists, prokaryotes, fungi, and, often, viruses. Microorganisms are a useful research tool as genetic vectors and, in immunology, for antibiotic susceptibility testing, cellular biology and genetics. Microorganisms commonly grow readily in incubators with microbial culture media; this can contain chromogenic supplements to differentiate between cell lines. Estimate your culture’s density of microorganisms with colony counters, or screen and select colonies for desirable clones with automated colony pickers. Additionally, equipment is available to monitor environments for the presence of microbes and identify with microbial identification instruments. Find the best microbiology products in our peer-reviewed product directory: compare products, check customer reviews and receive pricing direct from manufacturers.Cell-Based AssaysCell-based assays are used to monitor the presence, quantity and activities of a desired cellular analyte including drug molecules or biomarkers. This can reveal information on cell health (apoptosis, cytotoxicity, viability and proliferation assays), cell metabolism, cell migration and cell signaling mechanisms. Find the best cell-based assay products, kits and equipment with our peer reviewed product directory: compare products, check customer reviews and receiving pricing direct from manufacturers.Clostridium difficileAntimicrobialsBacteriaBacteria are microorganisms that play critical roles in the environment, human health, and biotechnology. Understanding bacterial genetics, growth, and metabolism is essential for developing antibiotics, vaccines, and improving industrial processes. Browse our peer-reviewed product directory to find the best bacterial research tools, compare products, check reviews, and get pricing directly from manufacturers.MutationMutations are changes in the DNA sequence that can lead to diseases, including cancer and genetic disorders. Analyzing mutations is crucial in diagnostics, drug development, and personalized medicine. Explore mutation detection tools in our peer-reviewed product directory; compare products, check reviews, and get pricing directly from manufacturers.AntibioticsAntibiotics are substances that kill or inhibit the growth of microorganisms, such as bacteria and fungi. They are essential in the treatment of infections and in preventing disease spread. Explore antibiotics research and diagnostic tools in our peer-reviewed product directory; compare products, check reviews, and get pricing directly from manufacturers.Antibiotic ResistanceAntibiotic resistance poses a significant threat to public health driving innovation and change through antibiotic stewardship efforts. Ongoing research and diagnostic efforts focus on new treatments and detection methods. Explore antibiotic resistance research and diagnostic tools in our peer-reviewed product directory; compare products, check reviews, and get pricing directly from manufacturers.Drug DevelopmentDrug development refers to the process of bringing a new drug to market.Infectious DiseasesInfectious diseases are caused by pathogens such as bacteria, viruses, and fungi. Effective detection, prevention, and treatment are crucial to control outbreaks and improve public health. Diagnostic tools, vaccines, and antimicrobial treatments are essential components of managing these diseases. Research into emerging pathogens and resistance patterns continues to evolve. Browse our peer-reviewed product directory to find the best diagnostic tools, prevention solutions, and treatment options; compare products, read customer reviews, and get pricing directly from manufacturers.
Combating C. difficile resistance development with novel combinations of antimicrobials