Anamika Bhattacharyya

Antibiotic-resistant acne: getting under the skin.

Propionibacterium acnes is a key pathogenic factor in the development of acne. Antibiotics are the first choice of treatment for mild-to-moderate, mixed, papular/pustular, and moderate nodular acne, and an alternative choice in severe, nodular/conglobate acne. The emergence of resistance to the currently available antibiotics poses a serious set-back to this algorithm, and the reduced arsenal can diminish efficacy of treatment. This emerging situation should catalyze innovations in dermatology; for example, newer drugs and technologies such as next-generation antibiotics with excellent potency and low propensity to develop resistance, rapid diagnostic platforms to select responders and nonresponders, and delivery technologies that target the bacteria. Such innovations can dramatically expand the arsenal for dermatologists in the management of acne.

A Rationally Designed Multifunctional Antibiotic for the Treatment of Drug-Resistant Acne

Acne is a multifactorial skin disease, underpinned by colonization of Propionibacterium acnes and inflammation. The emergence of resistant P.xa0acnes strains has affected the current acne treatment algorithm. This setback served as an impetus for rationally designing a library of next-generation antibiotics that exhibit a bactericidal effect on resistant P.xa0acnes and exert an immunomodulatory function to reduce inflammation. In silico screening showed that one of the molecules, VCD-004, exhibits improved mode of binding to bacterial DNA gyrase. VCD-004 shows high potency against clinical isolates of resistant P.xa0acnes and excellent efficacy inxa0vivo. Furthermore, VCD-004 exhibits a superior mutant prevention index, suggesting that it impedes the development of resistance better than clindamycin. Additionally, it shows optimal skin penetration and has a potent anti-inflammatory effect via reduction of proinflammatory cytokines (IL-6) independent of its antibacterial action. VCD-004 affects P.xa0acnes-induced nuclear accumulation of NF-κB in THP-1 cells. The inxa0vitro viability of human keratinocytes in the presence of VCD-004 indicates a desirable therapeutic window for topical use. Such rationally designed bactericidal and immunomodulatory dual pharmacophore-based lipophilic molecule(s) can emerge as the next-generation topical therapy for acne with underlying resistant P.xa0acnes etiology.

Evaluation of therapeutic potential of VB-001, a leave-on formulation, for the treatment of moderate adherent dandruff

BackgroundDandruff is a common scalp condition characterized by excessive scaling and itch. Aberrant colonization of the scalp by commensal Malassezia spp. is a major contributor in the multifactorial etiology of dandruff. Literature based understanding of Malassezia linked pathophysiology of dandruff allowed us to comprehend a strategy to potentiate the efficacy of a known antifungal agent used in dandruff therapy.The aim of this study was to determine the efficacy and skin safety of VB-001 antidandruff leave-on formulation in comparison with marketed antidandruff ZPTO shampoo in patients with moderate adherent dandruff of the scalp.MethodsHealthy males or females agedu2009≥u200915xa0years andu2009≤u200965 with a clinical diagnosis of moderate adherent dandruff of the scalp were recruited for the study to monitor the effects of topical VB-001 versus those of marketed antidandruff ZPTO shampoo.Results168 subjects were randomized to the treatment (VB-001, nu2009=u200984) and control (ZPTO shampoo, nu2009=u200984) groups. The efficacy of each product was evaluated by comparing proportion of subjects who have shown reduction in flaking by ASFS (adherent scalp flaking score) and pruritus by IGA (investigator global assessment) score. VB-001 imparted consistently better reduction in ASFS and enabled early reduction of pruritus in comparison to marketed ZPTO shampoo.ConclusionVB-001, a leave-on formulation with ingredients chosen to selectively disturb the Malassezia niche on dandruff scalp by denying extra nutritional benefits to the microbe, provides unique advantages over existing best in class ZPTO shampoo therapy. It has the potential to emerge as an attractive novel treatment for moderate adherent dandruff.Trial registrationCTRI Registration number: CTRI/2013/01/003283. Registered on: 02/01/2013