Efficacy of phage cocktail AB-SA01 therapy in diabetic mouse wound infections caused by multidrug-resistantStaphylococcus aureus

被引:60
作者
Kifelew, Legesse Garedew [1 ,2 ]
Warner, Morgyn S. [3 ,4 ]
Morales, Sandra [5 ]
Vaughan, Lewis [6 ]
Woodman, Richard [7 ]
Fitridge, Robert [8 ]
Mitchell, James G. [1 ]
Speck, Peter [1 ]
机构
[1] Flinders Univ S Australia, Coll Sci & Engn, Adelaide, SA, Australia
[2] St Pauls Hosp, Millennium Med Coll, Addis Ababa, Ethiopia
[3] Queen Elizabeth Hosp, Infect Dis Unit, Woodville, SA, Australia
[4] Univ Adelaide, Fac Med, Adelaide, SA, Australia
[5] AmpliPhi Biosci Corp, Sydney, NSW, Australia
[6] Flinders Univ S Australia, Res Dev & Support, Adelaide, SA, Australia
[7] Flinders Univ S Australia, Coll Med & Publ Hlth, Adelaide, SA, Australia
[8] Univ Adelaide, Discipline Surg, Adelaide, SA, Australia
关键词
Diabetic mice; Infection; MDRS; aureus; Phage cocktail; Treatment; Wound; STAPHYLOCOCCUS-AUREUS; BACTERIOPHAGE THERAPY; FOOT INFECTIONS; STREPTOZOTOCIN; MANAGEMENT; ULCERS;
D O I
10.1186/s12866-020-01891-8
中图分类号
Q93 [微生物学];
学科分类号
071005 ; 100705 ;
摘要
Background Diabetic foot ulcer (DFU) is a serious complication of diabetes mellitus. Antibiotic-resistantStaphylococcus aureusis frequently isolated from DFU infections. Bacteriophages (phages) represent an alternative or adjunct treatment to antibiotic therapy. Here we describe the efficacy of AB-SA01, a cocktail of threeS. aureus Myoviridaephages, made to current good manufacturing practice (cGMP) standards, and which has undergone two phase I clinical trials, in treatment of multidrug-resistant (MDR)S. aureusinfections. Results Wounds of saline-treated mice showed no healing, but expanded and became inflamed, ulcerated, and suppurating. In contrast, AB-SA01 treatment decreased the bacterial load with efficacy similar or superior to vancomycin treatment. At the end of the treatment period, there was a significant decrease (p < 0.001) in bacterial load and wound size in infected phage- and vancomycin-treated groups compared with infected saline-treated mice. In phage-treated mice, wound healing was seen similar to vancomycin treatment. No mortality was recorded associated with infections, and post-mortem examinations did not show any evident pathological lesions other than the skin wounds. No adverse effects related to the application of phages were observed. Conclusion Topical application of phage cocktail AB-SA01 is effective, as shown by bacterial load reduction and wound closure, in the treatment of diabetic wound infections caused by MDRS. aureus. Our results suggest that topical phage cocktail treatment may be effective in treating antibiotic-resistantS. aureusDFU infections.
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页数:10
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