Efficacy of a topical concentrated surfactant gel on microbial communities in non‐healing diabetic foot ulcers with chronic biofilm infections: A proof‐of‐concept study

Abstract

This proof-of-concept study sought to determine the effects of standard of care (SOC) and a topically applied concentrated surfactant gel (SG) on the total microbial load, community composition, and community diversity in nonhealing diabetic foot ulcers (DFUs) with chronic biofilm infections. SOC was provided in addition to a topical concentrated SG, applied every 2 days for 6 weeks. Wound swabs were obtained from the base of ulcers at baseline (week 0), week 1, mid-point (week 3), and end of treatment (week 6). DNA sequencing and real-time quantitative polymerase chain reaction (qPCR) were employed to determine the total microbial load, community composition, and diversity of patient samples. Tissue specimens were obtained at baseline and scanning electron microscopy and peptide nucleic acid fluorescent in situ hybridisation with confocal laser scanning microscopy were used to confirm the presence of biofilm in all 10 DFUs with suspected chronic biofilm infections. The application of SG resulted in 7 of 10 samples achieving a reduction in mean log10 total microbial load from baseline to end of treatment (0.8 Log10 16S copies, ±0.6), and 3 of 10 samples demonstrated an increase in mean Log10 total microbial load (0.6 log10 16S copies, ±0.8) from baseline to end of treatment. Composition changes in microbial communities were driven by changes to the most dominant bacteria. Corynebacterium sp. and Streptococcus sp. frequently reduced in relative abundance in patient samples from week 0 to week 6 but did not disappear. In contrast, Staphylococcus sp., Finegoldia sp., and Fusobacterium sp., relative abundances frequently increased in patient samples from week 0 to week 6. The application of a concentrated SG resulted in varying shifts to diversity (increase or decrease) between week 0 and week 6 samples at the individual patient level. Any shifts in community diversity were independent to changes in the total microbial loads. SOC and a topical concentrated SG directly affect the microbial loads and community composition of DFUs with chronic biofilm infections.

A metatranscriptomic approach to explore longitudinal tissue specimens from non‐healing diabetes related foot ulcers

“…We observed that RN7SL1 upregulation is predominantly limited to midpoint samples except for P9 which showed continual upregulation to the end of treatment. Potential suppression of p53 through RN7SL1 and enrichment of IGHG4 may indicate that treatment with conservative sharp debridement and a topical CSG were successful in removing or destabilizing microbial communities which is supported by our previous work [9]. The downstream effects of this may be altered pathways supressing cellular senescence and apoptosis and favouring cell activity/proliferation.…”

“…Ten patients were recruited from a high‐risk foot service as part of a previously published study on chronic DRFUs [9]. Punch biopsies from foot ulcer tissue were obtained prior to treatment (baseline), after 3 weeks of treatment (midpoint) and after 6 weeks of treatment (study endpoint).…”

“…The six individuals with chronic DRFUs in this study all had previously confirmed microbial aggregates/biofilms within DRFU tissue using scanning electron microscopy (SEM) and peptide nucleic acid fluorescence in situ hybridisation (PNA‐FISH) [9]. All individuals were provided with offloading devices (removable CAM walkers), but compliance with activity reduction or with wearing the offloading device was not quantified.…”

“…Participants from a previously reported clinical study [9] had additional tissue specimens obtained for the purpose of performing total RNA‐sequencing. Individuals aged over 18 years presenting with a chronic DRFU were prospectively recruited over an 18‐month period.…”

Challenges in the diagnosis and management of wound infection

“…Briefly, a highly concentrated, nonionic surfactant gel utilizing a poloxamer polymer (Plurogel TM ) has been reported to effectively remove or kill mature bacterial biofilms of several major bacterial pathogens grown on pig skin dermal wound explants, 55 and in reducing the total microbial loads of diabetic foot ulcers complicated with biofilms in vivo. 56 Sustained-release iodine dressings (Ioplex TM , Iodosorb TM , Iodoflex TM ) produced full kill of mature biofilms in laboratory and animal models and in clinical studies. [57][58][59] Negative-pressure wound therapy (NPWT) has been shown to improve healing of many types of challenging acute and chronic wounds.…”