Novel drugs and/or new approaches to combat infective fungi and overcome fungal resistance are urgently needed. Pay attention to the interactions between different drugs is an economical method. Creative Biolabs provides in vitro assays to measure the effect of combined drugs for fungal activities in the ways of synergistic and antagonistic.

Combination antifungal therapy has stimulated renewed interest in recent years. As the limitation of effective antifungal drugs, the combinations of polyene-, extended-spectrum azole-, and echinocandin-based treatment have produced a new therapeutic way for difficult-to-treat high mortality mold infections.

However, the use of two or more effective drugs with different mechanisms of action not always results in an improved efficiency (synergy effect) compared to the utilization of a single agent. Combination antifungal therapy could have addictive, indifferent or even antagonistic effects, which means a combination of the two or more drugs may reduce antifungal killing efficacy and increase the potential for drug-drug interactions. Thus, it is important to evaluate the role of combination therapy critically.

Creative Biolabs provides combination antifungal therapy service to evaluate synergy, indifferent and antagonistic effects of two or more drugs. The index we evaluate including the following:

Minimum Inhibitory Concentration (MIC) and Minimum Fungicidal Concentration (MFC)

MIC determination is a standard method treat as an index to determine the in vitro fungal susceptibility. We offer you broth microdilution assays, Etest assay, disk diffusion test and high throughput automatic instrumentation system to determine MICs for each drug and drug combinations. The MFC also can be identified in this process.

Quantitative Analyses by Fractional Inhibitory Concentration Index (FICI)

We calculate the fractional inhibitory concentration (FIC) index (FICI) to quantitative characterize the activity of antimicrobial combinations. The FICI represents the sum of the FICs of each drug tested. The calculation is showed in Figure 1.

Antifungal Synergistic and Antagonistic Effects Testing Figure 1. The following formulas using the results of MICs to calculate the fractional inhibitory concentration (FIC)

Our interpretation of the FIC results, according to accepted criteria were as follows:

  • Synergy - no more than 0.5
  • Additivity - 0.5 to 1.0
  • Indifference - 1.0 to 4.0
  • Antagonism - over 4

Antifungal Time-Kill Testing

The kill curves are constructed by plotting the CFU per milliliter surviving at each time point and compared the results of presence and absence of the antimicrobial agent. For determining synergy or antagonism effects between two or more antifungal drugs, kill curves are constructed for a fixed concentration of each agent alone and in combination and are compared to that of the no-drug control at each time point.

Creative Biolabs offers several antifungal pharmacodynamics services. For more detailed information, please feel free to contact us or directly sent us an inquiry.

Reference

  1. Johnson MD, MacDougall C, Ostrosky-Zeichner L, et al. (2004). “Combination antifungal therapy.” Antimicrob Agents Chemother. 48(3):693-715.
  2. Singh N and Mishra N (2012). “Synergistic and antagonistic action of antibiotics against biofilm forming Staphylococcus aureus”. Asian Journal of Plant Science and Research 2 (3):350-354

For lab research use only.



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