In vitro activity of the novel echinocandin CD101 at pH 7 and 4 against Candida spp. isolates from patients with vulvovaginal candidiasis.
The novel echinocandin CD101 has stability properties amenable to topical formulation for use in the treatment of acute vulvovaginal candidiasis (VVC) and recurrent VVC (RVVC). CD101 has demonstrated potent antifungal activity at pH 7, but assessment of its activity at the physiological pH of the vaginal environment is needed.



To evaluate the antifungal activity of CD101 against clinical VVC isolates of Candida spp., including azole-resistant strains, at pH 4.



MIC values of CD101 and comparators (fluconazole, itraconazole, micafungin, caspofungin and anidulafungin) were assessed via broth microdilution. MIC assays were conducted at pH 7 and 4 after 24 and 48 h against a 108 VVC isolate panel of Candida spp., including Candida albicans ( n  =   60), Candida glabrata ( n  =   21), Candida parapsilosis ( n  =   14) and Candida tropicalis ( n  =   13).



Overall, MIC values of all drugs were slightly higher at pH 4 versus 7 and at 48 versus 24 h of incubation. CD101 MIC values typically exhibited ∼4-fold shifts at pH 4 and were not affected by azole susceptibility. C. parapsilosis susceptibility was the least affected at pH 4 and did not increase for most drugs.



CD101 had potent activity against all Candida isolates tested, including azole-resistant strains. Although there was some reduction in activity at pH 4 versus 7, the resulting MIC values were still well below the intravaginal CD101 drug concentrations anticipated to be present following topical administration. These results support continued development of topical CD101 for the treatment of VVC/RVVC.
Division of Infectious Diseases, Wayne State University School of Medicine, 540 E. Canfield St., Detroit, MI 48201, USA.
Dina A
DA
Boikov
Cidara Therapeutics, Inc., 6310 Nancy Ridge Dr., Suite 101, San Diego, CA 92121, USA.
Jeffrey B
JB
Locke
Seachaid Pharmaceuticals, 801 Capitola Dr. # 5, Durham, NC 27713, USA.
Kenneth D
KD
James
Cidara Therapeutics, Inc., 6310 Nancy Ridge Dr., Suite 101, San Diego, CA 92121, USA.
Ken
K
Bartizal
Division of Infectious Diseases, Wayne State University School of Medicine, 540 E. Canfield St., Detroit, MI 48201, USA.
Jack D
JD
Sobel
D000935:Antifungal Agents / Q000494:pharmacology*; D001393:Azoles / Q000494:pharmacology; D002175:Candida / Q000187:drug effects* / Q000302:isolation & purification; D002176:Candida albicans / Q000187:drug effects / Q000302:isolation & purification; D041221:Candida glabrata / Q000187:drug effects / Q000302:isolation & purification; D041022:Candida tropicalis / Q000187:drug effects / Q000302:isolation & purification; D002181:Candidiasis, Vulvovaginal / Q000382:microbiology*; D000077336:Caspofungin; D025141:Drug Resistance, Fungal; D054714:Echinocandins / Q000737:chemistry / Q000494:pharmacology*; D005260:Female; D006801:Humans; D006863:Hydrogen-Ion Concentration; D055666:Lipopeptides / Q000494:pharmacology; D000077551:Micafungin; D008826:Microbial Sensitivity Tests
D000935:Antifungal Agents; D001393:Azoles; D054714:Echinocandins; D055666:Lipopeptides; D000077336:Caspofungin; D000077551:Micafungin