Potential of combination therapy of endolysin MR-10 and minocycline in treating MRSA induced systemic and localized burn wound infections in mice.
MRSA is the predominant pathogen responsible for fatal burn wound infection in patients. Antibiotic resistance and its ability to form biofilms on the surface of burn wounds limit the use of antibiotics to contain this pathogen. The results of present study have shown that single dose of combination therapy of endolysin MR-10 (50μg/s.c) and minocycline (50mg/kg/orally) resulted in 100% survival of group of mice with systemic MRSA infection. Maximum reduction in bacterial load in various organs was observed in the group that received combination therapy. In comparison to control, a significant reduction (p<0.01) of 4.82, 1.81, 1.51, 1.2 logs was observed in skin, blood, liver and spleen respectively, by 3rd day post infection. As a result of which, all organs became sterile thereby protecting mice from mortality. Histopathological analysis corroborated our findings showing no signs of inflammation and bacterial infection in the group that received combination therapy. Treatment of localized burn wound infection with combination therapy resulted in early resolution of infection followed by fast healing. The group that received combination therapy showed complete resolution of infection in less than 10days. Moreover, the skin samples obtained from animals treated with combination therapy showed no myeloperoxidase (MPO) activity on 10th day post treatment. In combination therapy group, ∼98% wound contraction was observed by 12th day followed by complete closure of wound within ∼14days. The histopathological analysis showed no signs of inflammation and infection. Collagen staining revealed early signs of re-epithelization of epidermis and signs of collagen regeneration in-group that received combination therapy. Hence, this study suggests that the combined therapy of endolysin MR-10 and minocycline is a better option in controlling burn wound infections.
Department of Microbiology, Panjab University, Chandigarh 160014, India.
Shivani
S
Chopra
Department of Microbiology, Panjab University, Chandigarh 160014, India.
Kusum
K
Harjai
Department of Microbiology, Panjab University, Chandigarh 160014, India. Electronic address: sanjaychhibber8@gmail.com.
Sanjay
S
Chhibber
D000284:Administration, Oral; D000825:Animal Structures / Q000382:microbiology; D000818:Animals; D000900:Anti-Bacterial Agents / Q000008:administration & dosage*; D058491:Bacterial Load; D002056:Burns / Q000150:complications; D004195:Disease Models, Animal; D004359:Drug Therapy, Combination / Q000379:methods; D010450:Endopeptidases / Q000008:administration & dosage*; D005260:Female; D006651:Histocytochemistry; D007279:Injections, Subcutaneous; D055624:Methicillin-Resistant Staphylococcus aureus / Q000187:drug effects*; D008807:Mice, Inbred BALB C; D008911:Minocycline / Q000008:administration & dosage*; D018805:Sepsis / Q000188:drug therapy* / Q000382:microbiology; D013203:Staphylococcal Infections / Q000188:drug therapy*; D016019:Survival Analysis; D013997:Time Factors; D016896:Treatment Outcome; D014946:Wound Infection / Q000150:complications / Q000188:drug therapy* / Q000382:microbiology
D000900:Anti-Bacterial Agents; D010450:Endopeptidases; C001143:endolysin; D008911:Minocycline
Burn wounds; Lysin; MRSA; Minocycline