Impetigo Animal Models: A Review of Their Feasibility and Clinical Utility for Therapeutic Appraisal of Investigational Drug Candidates

Abstract

Impetigo (school sores), a superficial skin infection commonly seen in children, is caused by the gram-positive bacteria Staphylococcus aureus and/or Streptococcus pyogenes. Antibiotic treatments, often topical, are used as the first-line therapy for impetigo. The efficacy of potential new antimicrobial compounds is first tested in in vitro studies and, if effective, followed by in vivo studies using animal models and/or humans. Animal models are critical means for investigating potential therapeutics and characterizing their safety profile prior to human trials. Although several reviews of animal models for skin infections have been published, there is a lack of a comprehensive review of animal models simulating impetigo for the selection of therapeutic drug candidates. This review critically examines the existing animal models for impetigo and their feasibility for testing the in vivo efficacy of topical treatments for impetigo and other superficial bacterial skin infections.

Comparison of Antibacterial Activity and Wound Healing in a Superficial Abrasion Mouse Model of Staphylococcus aureus Skin Infection Using Photodynamic Therapy Based on Methylene Blue or Mupirocin or Both

“…Our abrasive skin wound is more similar to real infection than tape stripping (45) and needs a higher bacterial inoculum (21,34). Clinically, is very similar to human impetigo, with a purulent infection established in 24 h, dermis affection and pyogranuloma during maturation of S. aureus at 48 h, epidermal purulent micro-abscess (72 h) and contraction and large crust of purulent material with histopathological hyperkeratosis (96 h) (18,46,47). Wounds healed per se appear with significative thickening of skin layers and dermal epithelial cysts, typical of this hairless mouse model, and clinically with desquamation and hypertrophic scar (16,23,48).…”

“…This apparent discordance between microbiological and clinical healing has been previously reported in Wistar rats, where topical MU shows efficacy against wound infection inoculated with S. aureus ( 50 ). Furthermore, the count of bacteria from infected mice may be inconsistent ( 51 ) and for that reason, other methods can be recommended in addition as bioluminescent monitoring ( 52 ) or the culture of supernatant of skin ( 47 ).…”

“…Correlations as size lesion and bacterial count in this SKH-1 model ( 78 ), size lesion changes and healing during aPDT treatment ( 79 ) were corroborated. Self-limiting of this model ( 23 ), related with experimental factors (skin reparation), promotes the clearing of bacteria ( 10 , 40 ); being a disadvantage to achieve a most robust model of skin S. aureus infection, on the other hand the lack of epidermis is an excellent model of repeated abrasion caused by human scratching ( 47 ). A more robust model of infection may find more synergistic results that those presented here.…”

“…Antimicrobial failure and synergy response were cited ( 80 , 81 ). Nevertheless, this model has two main limitations: first, the fact that even without treatment the infection and the wound cured in an immunocompetent model ( 47 ) although correlation of clinical events and histopathological findings are strong in staphylococcal infections ( 78 ), second, the lack of males, because both skin layer differences by gender have been described ( 18 , 82 ). Additionally, biological variability of SKH-1 hairless mice ( 23 ) during wound healing ( 66 ) should be considered.…”

Mathematical model and stability analysis on the transmission dynamics of skin sores

“…Impetigo has increased occurrence in close contact, warm and humid environments [ 10 ]. In vitro investigations are used to assess the efficacy of prospective novel antimicrobial agents, with in vivo studies in animal models and/or people following if they are successful [ 11 ]. According to recent estimates, impetigo affects anywhere from 111 million children in impoverished nations to 140 million people worldwide at any given moment [ 12 ].…”