Compounding Options for Patients with Resistant Yeast Infections
Many patients are faced with resistant fungal infections after many treatment failures. Currently, one of the most prevalent resistant Candida strains is C. glabrata, which is 10-100 times less susceptible to all azoles compared with C. albicans. The culture and sensitivity tests usually reveal that C. glabrata has a reduced susceptibility to amphotericin B, but sensitive to flucytosine. An earlier study of compounded flucytosine vaginal cream was associated with a successful outcome in 27 of 30 women (90%) whose condition had failed to respond to boric acid and azole therapy.1 There are compounded options for patients with resistant yeast infections. Below are a few Compounding Pharmacy Options for Patients with Resistant Yeast Infections.
Example Formula Flucytosine 15% Vaginal Cream (PCCA MucoLox™/PCCA VersaBase®)
However, this option is very costly to the patient (in some cases, $1000 or more) and therefore limits access for many patients. This hard-faced reality can leave you asking what other options are available. Many also wonder why C. glabrata is resistant. The overuse of antibiotics certainly contributes to the massive problem, but the fungal biofilms are an enormous barrier.2 Numerous clinical observations and experimental studies show that the currently available antifungal agents may not be effective in completely eliminating biofilm-related fungal infections.
Compounded medicine for Vaginal Yeast infections: EDTA, BORIC ACID, FLUCYTOSINE.
EDTA is considered a bio-film disrupter. The effect of EDTA on yeasts is said to act by binding with the magnesium and calcium ions of the membrane, with the different efficacies of EDTA being attributed to the different yeast species. The antifungal activity of EDTA is said to be likely via the inhibitory effect on growth, causing fungal death by competing with siderophores for any of the trace iron and calcium ions that are essential for the maintenance of the life cycle of fungi. Another important point is that the transformation of Candida from the diploid state to the hyphae formation is attenuated in media containing low Ca2+. 3 Therefore, EDTA not only can break down bio-films, but also prevents the fungi from transforming into the pathogenic state. A recent study for a forthcoming commercial product found that boric acid enhanced with EDTA was more effective at inhibiting C. albicans and C. glabrata fungal burden/biofilm formation on vaginal mucosa ex vivo than boric acid alone.4 These findings are consistent with another published study showing the same advantage, with robust destruction of biofilms formed by C. albicans and G. vaginalis in CDC biofilm reactors. An ex vivo study of boric acid with EDTA against G. vaginalis, a key BV pathogen, is ongoing.
Example Formula Boric Acid 30%/EDTA 0.5% Vaginal Gel (PCCA MucoLox/PCCA VersaBase)
For more information, please contact our clinical compounding pharmacists. We are happy to help with Compounding Pharmacy Options for Patients with Resistant Yeast Infections.
1. Sobel, J. D., Chaim, W., Nagappan, V., & Leaman, D. (2003). Treatment of vaginitis caused by Candida glabrata: Use of topical boric acid and flucytosine. American Journal of Obstetrics & Gynecology, 189(5), 1297- 1300. http://dx.doi.org/10.1067/S0002-9378(03)00726-9
2. Katragkou, A., Roilides, E., & Walsh, T. J. (2016). Can repurposing of existing drugs provide more effective therapies for invasive fungal infections? [Editorial]. Expert Opinion on Pharmacotherapy, 17(9), 1179-1182. http:// dx.doi.org/10.1080/14656566.2016.1186647
3. Brand, A., Shanks, S., Duncan, V. M. S., Yang, M., Mackenzie, K., & Gow, N. A. R. (2007). Hyphal orientation of Candida albicans is regulated by a calcium-dependent mechanism. Current Biology, 17(4), 347-352. https:// doi.org/10.1016/j.cub.2006.12.043
4. Fidel, P., Jr., & Lilly, E. (2015). Activity of TOL-463 against biofilms formed by Candida species in an ex vivo murine vaginitis model [Poster abstract]. Open Forum Infectious Diseases, 2(Suppl 1), S149. Retrieved from https://www. researchgate.net/publication/313291125_Activity_of_TOL-463_Against_ Biofilms_Formed_by_Candida_Species_in_an_Ex_Vivo_Murine_Vaginitis_Model