Co-therapy using lytic bacteriophage and linezolid: effective treatment in eliminating methicillin resistant Staphylococcus aureus (MRSA) from diabetic foot infections

• Published in: PloS one 2013-02, Vol.8 (2), p.e56022-e56022
• Main Authors: Chhibber, Sanjay, Kaur, Tarsem, Sandeep Kaur
• Format: Article
• Language: English
• Subjects: Acetamides - therapeutic use; Alloxan; Analysis; Animals; Anti-Bacterial Agents - pharmacology; Anti-Bacterial Agents - therapeutic use; Anti-Infective Agents - therapeutic use; Antibiotics; Arresting (process); Bacteria; Bacterial infections; Bacteriophages; Biology; Costs; Diabetes; Diabetes mellitus; Diabetes Mellitus, Experimental - complications; Diabetes Mellitus, Experimental - drug therapy; Diabetes Mellitus, Experimental - microbiology; Diabetic foot; Diabetic Foot - complications; Diabetic Foot - drug therapy; Diabetic Foot - microbiology; Diabetic neuropathy; Diabetics; Drug resistance; Edema; FDA approval; Feet; Foot diseases; Health aspects; Host range; Immunology; Immunosuppression; Infection; Infections; Infectious diseases; Laboratories; Linezolid; Medicine; Methicillin; Methicillin-Resistant Staphylococcus aureus - isolation & purification; Mice; Mice, Inbred BALB C; Microbial drug resistance; Mortality; Mutants; Neutrophils; Oxazolidinones - therapeutic use; Patients; Peroxidase; Phages; Pneumonia; Public health; Resistant mutant; Staphylococcal Skin Infections - complications; Staphylococcal Skin Infections - drug therapy; Staphylococcal Skin Infections - microbiology; Staphylococcus aureus; Staphylococcus aureus infections; Staphylococcus infections; Strains (organisms); Therapy; Treatment Outcome; Type 2 diabetes; Ulcers; Wound healing
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0056022

Staphylococcus aureus remains the predominant pathogen in diabetic foot infections and prevalence of methicillin resistant S.aureus (MRSA) strains further complicates the situation. The incidence of MRSA in infected foot ulcers is 15-30% and there is an alarming trend for its increase in many countries. Diabetes acts as an immunosuppressive state decreasing the overall immune functioning of body and to worsen the situation, wounds inflicted with drug resistant strains represent a morbid combination in diabetic patients. Foot infections caused by MRSA are associated with an increased risk of amputations, increased hospital stay, increased expenses and higher infection-related mortality. Hence, newer, safer and effective treatment strategies are required for treating MRSA mediated diabetic foot infections. The present study focuses on the use of lytic bacteriophage in combination with linezolid as an effective treatment strategy against foot infection in diabetic population. Acute hindpaw infection with S.aureus ATCC 43300 was established in alloxan induced diabetic BALB/c mice. Therapeutic efficacy of a well characterized broad host range lytic bacteriophage, MR-10 was evaluated alone as well as in combination with linezolid in resolving the course of hindpaw foot infection in diabetic mice. The process of wound healing was also investigated. A single administration of phage exhibited efficacy similar to linezolid in resolving the course of hindpaw infection in diabetic animals. However, combination therapy using both the agents was much more effective in arresting the entire infection process (bacterial load, lesion score, foot myeloperoxidase activity and histopathological analysis). The entire process of tissue healing was also hastened. Use of combined agents has been known to decrease the frequency of emergence of resistant mutants, hence this approach can serve as an effective strategy in treating MRSA mediated foot infections in diabetic individuals who do not respond to conventional antibiotic therapy.