Combating <i>C. difficile</i> Resistance Development with Novel Combinations of Antimicrobials

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.

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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