title: Efficacy of NVC-422 in the treatment of dermatophytosis caused by Trichophyton mentagrophytes using a guinea pig model.
abstract: OBJECTIVE
  Dermatophytes, belonging to genera including Trichophyton, Epidermophyton, and Microsporum, are the causative agents of superficial fungal infections, prevalences of which are estimated to be as high as 25% in the worldwide population. This study evaluated the activity of topical formulations of NVC-422 (sodium 2-[dichloroamino]-2-methylpropane-1-sulfonate), the lead compound in a new class of antimicrobials that consist of broad-spectrum, fast-acting, nonantibiotic antimicrobial molecules based on the endogenously produced N-chlorotaurines.
  
  
  METHODS
  The antifungal efficacy of NVC-422 was investigated using a guinea pig model of infection with Trichophyton mentagrophytes. Infected guinea pigs were randomly assigned to four treatment and two control groups. The efficacy of the treatments was assessed clinically and mycologically at 72 hours after the final topical dose.
  
  
  RESULTS
  The test compound 2% NVC-422 in 1% Noveon Gel demonstrated the highest level of clinical efficacy. Outcomes of treatment with all other test compounds differed significantly from outcomes in the untreated control group (P = 0.003, P = 0.029, P = 0.012, and P < 0.0001, respectively). Fungal elements were detectable in skin sections from untreated guinea pigs but not in skin sections obtained from any of the treatment groups.
  
  
  CONCLUSIONS
  Evaluation of the efficacy of NVC-422 in the treatment of dermatophytosis using an experimental guinea pig model showed that this compound possesses potent antifungal efficacy as measured by mycological and clinical endpoints. The highest degree of clinical and mycological efficacy was demonstrated by 2% NVC-422 in 1% Noveon Gel. These data show that NVC-422 has potent antifungal activity in vivo. Clinical evaluation of NVC-422 in the treatment of superficial infections caused by dermatophytes, including onychomycosis, is warranted.
authors.affiliation: Center for Medical Mycology, Case Western Reserve University School of Medicine, Cleveland, OH 44106-5028, USA. mag3@case.edu
authors.forename: Mahmoud A
authors.initials: MA
authors.lastname: Ghannoum
authors.forename: Lisa
authors.initials: L
authors.lastname: Long
authors.forename: Amber J
authors.initials: AJ
authors.lastname: Cirino
authors.forename: Anthony R
authors.initials: AR
authors.lastname: Miller
authors.forename: Ron
authors.initials: R
authors.lastname: Najafi
authors.forename: Lu
authors.initials: L
authors.lastname: Wang
authors.forename: Kuldeepak
authors.initials: K
authors.lastname: Sharma
authors.forename: Mark
authors.initials: M
authors.lastname: Anderson
authors.forename: Bahram
authors.initials: B
authors.lastname: Memarzadeh
mesh_terms: D000818:Animals; D000935:Antifungal Agents / Q000008:administration & dosage / Q000627:therapeutic use*; D005782:Gels; D006168:Guinea Pigs; D008297:Male; D011897:Random Allocation; D013654:Taurine / Q000008:administration & dosage / Q000031:analogs & derivatives* / Q000627:therapeutic use; D014005:Tinea / Q000188:drug therapy* / Q000382:microbiology; D014249:Trichophyton
chemical_list: D000935:Antifungal Agents; D005782:Gels; D013654:Taurine; C560851:NVC-422