SANTA FE, N.M. – Of seven antifungal agents studied for the treatment of vulvovaginal Candida glabrata and Candida albicans infections, caspofungin and flucytosine remained stable as pH decreased to physiological levels, results from a novel in vitro study demonstrated.
In particular, caspofungin’s stability at a lower pH may "make it a promising candidate for topical treatment of complicated vulvovaginal candidiasis," Dr. Claire S. Danby said at the annual meeting of the Infectious Diseases Society for Obstetrics and Gynecology.
"The diagnosis of Candida glabrata can be challenging," said Dr. Danby, a third-year resident in the department of obstetrics and gynecology at Maine Medical Center, Portland. "Subjectively, the symptoms are more subtle and can be more mild. Objectively, patients with the condition can present with scant discharge or mild erythema. Eradication is quite difficult. We know that the infection demonstrates variable intrinsic resistance to azole drugs. And despite the fact that a lot of the time it can be successfully treated with boric acid, this is not curative in all patients. Also, Candida glabrata demonstrates a varied response to treatment with topical flucytosine, oral itraconazole, and vaginal suppositories."
Considering the fact that the vaginal pH of patients with vulvovaginal candidiasis remains unchanged at 4-4.5, Dr. Danby worked with Dr. Jack D. Sobel of the division of infectious diseases at Wayne State University, Detroit, to study the effect of pH on the in vitro activity of seven antifungal agents against 40 C. glabrata and 6 C. albicans clinical isolates from the microbiology lab at the university’s vaginitis clinic. They used CLSI (Clinical and Laboratory Standards Institute) broth guidelines to determine in vitro susceptibility to flucytosine, fluconazole, voriconazole, posaconazole, ciclopirox olamine, amphotericin B, and caspofungin. Solutions were buffered to a pH of 4, 5, 6, and 7, and minimum inhibitory concentrations (MICs) were recorded after 48 hours of incubation at 35??C.
Dr. Danby reported the MIC90 for a change in pH from 7 to 4. C. glabrata MICs for azoles increased from 32 to more than 64 mcg/mL for fluconazole, 0.5 to greater than 16 mcg/mL for voriconazole, and 0.5 to greater than 16 mcg/mL for posaconazole. MICs also increased for ciclopirox olamine (from 0.5 to 2 mcg/mL) and amphotericin B (from 0.25 to 4 mcg/mL), but remained constant for flucytosine (0.125 mcg/mL) and caspofungin (0.5 mcg/mL).
MICs of C. albicans remained stable at 0.03 mcg/mL for voriconazole and posaconazole, and increased for fluconazole (from 0.25 to 1 mcg/mL), ciclopirox olamine (from 0.5 to 2 mcg/mL) and amphotericin B (from 0.03 to 4 mcg/mL). MICs for flucytosine changed from 0.5 to 0.25 mcg/mL, and from 0.125 to 0.25 mcg/mL for caspofungin, with a decrease in pH from 7 to 4.
"All azoles showed dramatic class effect," Dr. Danby commented. "The effect of pH was most noticeable with C. glabrata. This may explain the frequent failure of fluconazole therapy."
Although caspofungin’s stability at the lower pH makes it a promising candidate for the topical treatment of complicated vulvovaginal candidiasis, the product "is not currently available in topical form," she said. "It’s only available in IV form."
Dr. Danby said that she had no financial conflicts to disclose.