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Combined therapy with amphotericin B and caspofungin in an experimental model of disseminated histoplasmosis
Gabriela Rodríguez-Arellanes1, María Lucía Taylor, Armando Pérez-Torres
1Departamento de Microbiología-Parasitología , Facultad de Medicina, Universidad Nacional Autónoma de Mexico. Departamentos de ***Bioquimica, ****Zoologia y *****Microbiologia, Escuela Nacional de Ciencias Biol6gicas, Instituto Polit&cnico Nacional.
Objective:
To assess the effect of amphotericin B and caspofungin, as well as their combinations in the therapy of experimental disseminated histoplasmosis.
Material And Methods:
BALB/c mice were intraperitoneally infected with four different strains of Histoplasma capsulatum and given to antifungal treatments. The response to intraperitoneal therapy with amphotericin B (0.5, 1.0, and 2.0 mg/kg of body weight) or caspofungin (10 mg/kg of body weight) and their combinations, was evaluated by the quantification of yeast colony-forming units (CFU) per gram of spleen or lung, from each animal. Additionally, the pathogen was monitored histopathologically in the excised organs. Data were analyzed with the Kruskall-Wallis and Tukey tests.
Results:
Caspofungin was more effective than amphotericin B in reducing the CFU/ g. A synergistic effect was observed when caspofungin (10 mg/ kg) was combined with amphotericin B (0.5 or 1.0 mg/kg). Significant differences in CFU values, H = 119.78 (P = 0.00001), were found among the treatment groups. However, statistical analyses did not reveal significant differences, H = 2.837 (P = 0.428), in the therapeutic responses with the four H. capsulatum strains tested.
Conclusion:
Combined therapy with amphotericin B and caspofungin could represent an alternative treatment to be explored in severe human histoplasmosis.
Insights
Caspofungin demonstrated superior efficacy over amphotericin B in treating experimental disseminated histoplasmosis. Combining caspofungin with amphotericin B showed synergistic effects, suggesting a potential alternative therapy for severe cases.
Area of Science:
- Mycology
- Infectious Diseases
- Pharmacology
Background:
- Histoplasmosis is a serious fungal infection caused by Histoplasma capsulatum.
- Current treatments, including amphotericin B, face challenges with efficacy and toxicity.
- Novel therapeutic strategies are needed for disseminated histoplasmosis.
Purpose of the Study:
- To evaluate the efficacy of amphotericin B and caspofungin, alone and in combination, against experimental disseminated histoplasmosis.
- To compare the effectiveness of these antifungal agents in reducing fungal burden in infected mice.
Main Methods:
- BALB/c mice were infected with Histoplasma capsulatum strains.
- Animals received intraperitoneal treatments of amphotericin B, caspofungin, or their combinations.
- Fungal burden was quantified by colony-forming units (CFU) in spleen and lungs; histopathological analysis was also performed.
Main Results:
- Caspofungin showed greater effectiveness in reducing fungal CFU compared to amphotericin B.
- A synergistic antifungal effect was observed when caspofungin was combined with lower doses of amphotericin B.
- While significant differences in CFU were found between treatment groups, no significant differences were observed across the four H. capsulatum strains tested.
Conclusions:
- Combined therapy with amphotericin B and caspofungin demonstrates synergistic potential.
- This combination therapy could offer a promising alternative treatment for severe human histoplasmosis.
- Further exploration of this combined regimen in clinical settings is warranted.
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