SLR - October 2019 - Rebecca S. Herman

Evidence of Differential Microbiomes in Healing Versus Non-Healing Diabetic Foot Ulcers Prior to and Following Foot Salvage Therapy

Reference: MacDonald A, Brodell JD JR, Daiss JL, Schwartz EM, Oh I. Evidence of Differential Microbiomes in Healing Versus Non-Healing Diabetic Foot Ulcers Prior to and Following Foot Salvage Therapy. J Orthop Res.  2019 Jul; 37 (7): 1596-1603

Scientific Literature Review

Reviewed By: Rebecca S. Herman, DPM
Residency Program: UNY Downstate Medical Center – Brooklyn, NY

Podiatric Relevance: Diabetic foot ulcerations (DFU) are a leading cause of non-traumatic lower extremity amputations. A greater understanding of an ulcers’ etiology may lead to improved treatment outcomes allowing for higher percentage of limb salvage. The combination of clinical signs of infection as well as nonspecific biomarkers of inflammation such as erythrocyte sedimentation rate and C-reactive proteins are currently employed to diagnose diabetic foot infection, but there are no specific measures to monitor a successful outcome of limb salvage. Past research has shown that microbial load, diversity, and pathogenicity plays a major factor in the delayed or non-healing of DFUs. This study aimed to evaluate if initial microbiomes, microbial load, diversity and presence of pathogenic organisms change in response to antibiotics treatment affect healing of DFU. Additionally, the study explores if the changes in DFU microbiome during treatment are prognostic of the clinical outcome.

Methods: This is a prospective observational study. Inclusion criteria included patients 18 years or older with Type I and II diabetes presenting with a diabetic foot infection. Infection was determined by more than two clinical signs of infection including inflammation, erythema, pain, calor, or purulent discharge. Twenty three patients underwent irrigation and debridement with tissue samples collected at initial debridement, four weeks, and eight weeks. Patients were placed on IV antibiotics for six weeks tailored to the wound culture. Tissue samples collected were analyzed using 16S rRNA genomic sequencing for microbial identification and quantitative PCR for the quantity of the bacterial amount.

Results: Of the 23 patients who completed the 12 week follow up, 11 patients healed whereas 12 patients did not heal. The healed group had greater percentage of Actinomycetales and Bacillales organisms. Greater abundance of Bacteroidales and Lactobacillales were present in the non healing group. Within Bacillales and Lactobacillales orders, the healed diabetic foot ulcers had greater percentage of Staphylococcaceae family as opposed to Streptococcaceae family. At four-week followup post irrigation and debridement and treatment of IV antibiotics, the non healed group continued to have more significant quantity of bacteria in bacteroidales in comparison to the healed group. At eight weeks with discontinuation of IV antibiotics, greater abundance of Actinomycetales was seen in healed group as compared to non healed group.

Conclusions: The authors conclude that genomic sequencing can offer a prognostic value to treating ulcers as patients that healed had a surplus of Actinomycetales and Staphyloccoccaceae family bacteria. Bacteroidales and Streptococcus are poor prognostic indicators for healing. Furthermore, antibiotic management alters the microbiome seen in the increased amount of Actinomycetales at eight weeks in healed group as opposed to initial and four weeks followup. These results will aid podiatrists and patients decision in performing limb salvage versus amputation. This study demonstrates that incorporating genomic sequencing in diagnosing and treating diabetic foot ulcers will lead to more effective treatments, knowledge for both patient and clinician, as well as better prognostic indicators. Further research is needed with a larger sample size and specific locations of ulceration. 

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