Hannah C Travers, Jonathon Dawson, Anitha Muthusami, Michael L Wall
Black Country Vascular Network, Dudley Group of Hospitals NHS Foundation Trust, West Midlands.
Address for correspondence: Miss Hannah C Travers
Black Country Vascular Network, Dudley Group of Hospitals NHS Foundation Trust, Pensnett Road, Dudley, West Midlands, DY1 2HQ
E-mail: hannah.travers@doctors.org.uk
https://doi.org/10.15277/bjd.2021.310
Introduction: Diabetes mellitus is a significant cause of morbidity and mortality. Foot-related complications affect 2–2.5% of people with diabetes. There is significant variation in outcomes for patients with diabetic foot disease within the UK. The multidisciplinary approach to diabetic foot disease is well publicised and protocols, guidance and consensus approaches exist for most components of the management of diabetic foot disease. Antimicrobial therapy to treat diabetic foot infections based on microbiological sampling and culture is well documented, but no consensus exists on how these samples should be obtained, processed and reported.
Methods: A literature review was undertaken to establish the reporting of techniques used in obtaining and processing microbiological samples in diabetic foot disease to establish if consensus exists in the methodologies used with a view to develop best practice guidelines.
Results: Six out of 102 papers reported all processes in obtaining and processing microbiological samples.
Conclusion: No gold standard consensus exists for microbiological sampling of diabetic foot infections, preventing optimisation of this aspect of management of diabetic foot disease and ultimately potentially adversely affecting the outcomes of this growing patient cohort.
Br J Diabetes 2021;21:233 - 236
Key words: diabetic foot; microbiology sampling; osteomyelitis
Diabetes mellitus is a significant cause of morbidity and mortality.1 Foot-related complications affect 2–2.5% of people with diabetes, equating to a point prevalence of approximately 58,000 people in England alone.2
There is significant regional variation in outcomes for patients with diabetic foot disease within the UK.3 The National Diabetes Foot Care Audit aims to quantify these variations at an organisational level so that markers of an effective service can be identified. However, low levels of participation have so far made it difficult to draw any consensus on this.4
The management of diabetic foot disease is complex, involving input from a multidisciplinary team of professionals.5 The mainstays of treatment in these challenging cases are off-loading of pressure areas and appropriate footwear, surgical debridement of infected and necrotic tissue, revascularisation if required, appropriate wound care and dressings, and antimicrobial therapy. Healthcare institutions managing diabetic foot disease should have clear pathways and guidance for management of these patients with alignment of services and processes to ensure the best patient outcomes and reduce major limb amputation rates and the associated morbidity and mortality.4
Each facet of the management of diabetic foot disease has been subject to review in the medical literature with consensus documents produced advising on the best practice for the treatment. The use of antimicrobial therapy and prolonged courses to treat osteomyelitis is well documented6 and should be based on tissue or bone sampling, culture and appropriate sensitivity testing cultures.5 However, how these samples should be obtained, processed and reported is poorly documented, making alignment of services difficult. Targeted antimicrobial therapy relies on certain steps to be completed, as demonstrated in Figure 1. Each of the steps shown has the potential to affect the subsequent accuracy of results and must be clearly described so accurate comparison can be made between techniques and results.
A literature review was undertaken to clarify the practice for reporting of tissue sampling techniques in the diabetic foot population and to determine if consensus exists in the literature for sampling techniques and processing, with the aim of developing best practice guidelines particularly in relation to the intraoperative bone sampling techniques used.
The NICE Healthcare Databases Advanced Search (https://hdas.nice.org.uk) was used to search EMBASE and Medline databases in September 2020. The search strategy is detailed in Appendix 1. Studies were restricted to human subjects, in the English language, published between 2010 and 2020 with an abstract available.
A total of 707 papers were identified. Duplicates, case reports and conference abstracts were removed and abstracts were screened by HT and JD for relevance and any conflicts were resolved by the senior author (MW). One hundred and forty-nine full-text articles were deemed relevant for review and 102 were included in the analysis. Figure 2 shows the PRISMA flow diagram.
Studies were reviewed by the authors and basic information was collected on the study type and population. The papers were reviewed for the following aspects of their methodology with a view to whether the study would be reproducible: what was sampled, how it was sampled, whether the wound was cleaned prior to sampling and how, how the specimen was transported for processing and what processing occurred. This information was compiled and analysed using Microsoft Excel (Windows 10).
Of the 707 papers identified through database searching, 123 duplicates and 109 case reports and conference abstracts were removed; 475 were screened by title and abstract and 326 were deemed irrelevant and excluded. Of the 149 full-text articles assessed for eligibility, a further 47 were excluded (reasons detailed in Figure 2). One hundred and two papers were included in qualitative analysis (see Appendix 2), of which 45 were prospective studies, 25 were retrospective studies and in 32 the time frame was unclear. There were 16 observational studies, 1 case series, 3 case–control studies, 55 cohort studies, 22 cross-sectional studies, 4 randomised controlled trials and 1 pilot study.
Eighty (78%) studies described the sampling technique used, 58 (57%) described how the wound was cleaned prior to sampling, 50 (49%) described how the specimen was kept prior to processing and 80 (78%) described the processing techniques used.
Samples taken
Wound or ulcer swabs only were performed in 26 of the papers and pus cultures in five. Bone sampling alone was used in 17 papers, tissue including skin in 17 and other samples in one paper. Thirty-one papers described more than one specimen type being taken.
Sampling technique
The percentage of papers reporting the use of different techniques for obtaining samples in the systematic review is shown in Table 1.
Wound cleaning
The percentage of papers reporting how the wound was cleaned prior to microbiology sampling is shown in Table 2.
Specimen transport
All three variables (time, medium, temperature) of transportation of specimens were reported in 6.9% of papers, 50% of papers detailed no information about how the specimen was kept or transported prior to processing, 22.5% of papers reported only one of the three transport variables (medium 15.7%, time frame 4.9%, temperature 2.0%) and 19% reported on two of the three variables. One paper stated that the specimens were transported by “conventional methods”.
Specimen processing
Detailed processing methods were described in 23.5% of papers, 30.4% stated “conventional methods” or “culture and sensitivity” were used, 18.6% made no comment about the processing techniques, 11.8% were sent for aerobic and anaerobic culture and 3.9% for aerobic culture only, and 11.8% of papers described molecular microbiological techniques.
Complete sampling protocols
Thirty-five papers (34%) described all four stages of microbiological sampling and processing and six papers (6%) sampled bone and described all four stages. These papers were all studies in patients with diabetic foot disease. The techniques described in these six papers are summarised in Appendix 3.
Diabetic foot disease is an international pandemic with a large socioeconomic burden on people and healthcare systems worldwide. Attempts to improve the treatment of diabetic foot disease have been ongoing throughout the medical community with identification of trends in microbiology and the best sampling techniques. Duration of antimicrobial therapy is guided by the culture and sensitivity of samples taken from active diabetic foot infections. Positive bone cultures attract a prolonged (6-week) course of antimicrobial therapy.7,8 Inappropriate use of antimicrobials is not without its morbidity and therefore accurate culture and sensitivity is imperative to optimise management.
The management of diabetic foot infection requires a multidisciplinary approach and it is the links between specialities that improve patient care. The authors, as surgeons, were concerned that the process by which specimens are sampled and transported to the laboratory for microbiological processing may well be impacting upon the reliability of results. Having standard operating procedures and protocols is well documented in healthcare to improve outcomes; however, there is no gold standard for microbiology sampling and processing to guide antimicrobial therapy in the management of diabetic foot disease. A standardised approach to the sampling process will reduce variation in technique and may help avoid inaccurate results, therefore leading to greater reliability and reproducibility.
There are some limitations to this study. It is a qualitative literature review rather than a systematic review due to the fact that the authors are examining methodology and reporting rather than study results. Non-English language studies were excluded and 12 studies were not available as full-text articles. This may have led to exemplary studies being excluded from this literature review but, if they are not readily available to clinicians treating diabetic foot disease internationally, it is difficult for their results to influence practice.
This literature review clearly demonstrates that there is no standardised methodology for reporting of specimen type, sampling method or processing methods for microbiological culture for the diagnosis and treatment of diabetic foot infection in the medical literature. This heterogeneous reporting means that it is difficult for readers and practitioners to draw accurate conclusions from the published literature in order to improve their own practice or to train the future generation of the multidisciplinary team managing this disease. A recent survey conducted by the author showed a lack of consistency in the sampling techniques in the trainee surgical community.9 It also demonstrated a lack of understanding of the processing techniques, procedural reporting and a lack of ongoing training in the surgical debridement of diabetic foot disease, specifically toe amputations.
The authors feel that a consensus must be sought for the sampling and processing of diabetic foot samples. The publication of papers in relation to microbiology sampling in diabetic foot disease must clearly delineate the steps in sampling, transportation and processing, making the studies transparent and reproducible. This will allow the reader to interpret the results and optimise all aspects of management of diabetic foot disease, allow for further studies into techniques, allow rationalisation of antimicrobial therapy and ultimately reduce the long-term sequelae, morbidity and mortality of diabetic foot disease.
Conflict of interest All authors have non to declare.
Funding None.
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7. Tone A, Nguyen S, Devemy F, et al. Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care 2015;38(2):302–7. https://doi.org/10.2337/dc14-1514
8. National Institute for Health and Care Excellence. Diabetic foot infection: antimicrobial prescribing. Evidence review. 2019. Available at: https://www.nice.org.uk/guidance/ng19/evidence/evidence-review-pdf-6953995118 (accessed 10 March 2021)
9. Dawson J, Travers HC, Wall ML. Level of training in microbiological sampling for toe amputations in diabetic foot disease: a survey of UK vascular trainees. Diabetic Foot J 2021 (accepted for publication).