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Postantifungal effect and effects of sub-MIC concentrations on previously treated Candida sp. influence of growth
M T García1, M T Llorente, F Mínguez
1Department of Microbiology, School of Medicine, Universidad Complutense, Madrid 28040, Spain.
Objectives:
This study evaluates the influence of growth phase on the postantifungal effect (PAFE) and on the effect of sub-MIC concentrations (1/4x MIC) on Candida sp. in PAFE stage (PAFSE).
Methods:
This stage was induced by pre-treatments of 1.5 h of C. albicans or C. glabrata in their exponential or stationary phase, with 1x, 4x or 8x MIC of four antifungal agents that are fundamental for modern candidiasis therapy.
Results:
Ketoconazole and fluconazole induced longer PAFSEs on microorganisms in logarithmic growth phase. However, this influence did not exist in the case of PAFSEs induced by AmB and 5-Fc or with the postantifungal effect induced by the four antifungal agents. In any way, significant PAFEs were always observed for Amphotericin B and 5-fluorocytosine (0.8-4.8 and 0.5-3 h, respectively, depending on the treatment dose). These values were increased (2.3-3.6 and 1.4-3.2 h respectively, depending on the pre-treatment dose) by posterior exposition to 1/4x MIC of the respective antifungal agent. In the case of ketoconazole and fluconazole, both antimycotics were not able to induce significant PAFEs, but posterior treatments to 1/4x MIC of each of the two azoles led in both yeast species to significant PAFSE of up to 2.6 h duration with ketoconazole, and 0.8 h with fluconazole, depending on the pre-treatment concentration.
Conclusion:
The growth phase of microorganisms should be considered in the planning of dosage protocols with azoles, because if the concentration applied is not high enough, the sub-MIC effects could be no significant for fungi in stationary phase of large wounds. Amphotericin B and 5-fluorocytosine induced significant postantifungal effect onCandida sp. This effect was increased by posterior exposition to sub-MIC concentration of the antifungal agents. Ketoconazole and fuconazole were not able to induce significant PAFEs at the concentrations tested, but posterior treatments to sub-MIC concentrations led to significant PAFSE. The growth phase of the culture at the time of its pre-treatment did not influence the length of the PAFE induced in it. However, the effect of the sub-MIC concentrations of Kz or Flu in yeast in PAFE phase was greater on yeast in exponential phase than for cultures in stationary phase.
Insights
The growth phase of Candida species influences antifungal drug effectiveness. Azoles show greater sub-inhibitory effects on exponential-phase fungi, while Amphotericin B and 5-fluorocytosine maintain significant post-antifungal effects regardless of growth phase.
Area of Science:
- Medical Mycology
- Antimicrobial Resistance
- Pharmacodynamics
Background:
- The post-antifungal effect (PAFE) and post-antifungal sub-MIC effect (PAFSE) are crucial parameters for evaluating antifungal drug efficacy.
- Candida species are significant human pathogens, and understanding factors influencing their susceptibility to antifungal agents is vital for effective treatment.
- The growth phase of microorganisms can impact their response to antimicrobial therapies.
Purpose of the Study:
- To investigate the influence of the growth phase (exponential vs. stationary) of Candida species on the induced post-antifungal effect (PAFE).
- To evaluate the impact of sub-inhibitory concentrations (1/4x MIC) on Candida species during the PAFE stage (PAFSE).
- To compare the effects of different antifungal agents (ketoconazole, fluconazole, Amphotericin B, 5-fluorocytosine) on PAFE and PAFSE across different growth phases.
Main Methods:
- Pre-treatment of Candida albicans and Candida glabrata cultures (exponential or stationary phase) for 1.5 hours with 1x, 4x, or 8x MIC of four antifungal agents.
- Induction of PAFE and PAFSE stages.
- Subsequent exposure to sub-inhibitory concentrations (1/4x MIC) of the respective antifungal agents to assess PAFSE.
Main Results:
- Ketoconazole and fluconazole induced longer PAFSEs in exponential-phase cultures compared to stationary-phase cultures.
- Amphotericin B and 5-fluorocytosine induced significant PAFEs regardless of growth phase, and these effects were enhanced by subsequent exposure to sub-MIC concentrations.
- Ketoconazole and fluconazole did not induce significant PAFEs at tested concentrations, but sub-MIC treatments led to significant PAFSE, particularly in exponential-phase yeast.
Conclusions:
- The growth phase of Candida species is a critical factor to consider when designing dosage protocols for azole antifungals.
- Amphotericin B and 5-fluorocytosine demonstrate robust PAFE and enhanced effects with sub-MIC exposure, irrespective of the fungal growth phase.
- Sub-MIC concentrations of ketoconazole and fluconazole can induce significant PAFSE, with greater efficacy observed in the exponential growth phase of Candida species.
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