Understanding the microbiome of diabetic foot osteomyelitis: insights from molecular and microscopic approaches.

OBJECTIVES: Rigorous visual evidence on whether or not biofilms are involved in diabetic foot osteomyelitis (DFO) is lacking. We employed a suite of molecular and microscopic approaches to investigate the microbiome, and phenotypic state of microorganisms involved in DFO. METHODS: In 20 consecutive subjects with suspected DFO, we collected intraoperative bone specimens. To explore the microbial diversity present in infected bone we performed next generation DNA sequencing. We used scanning electron microscopy (SEM) and peptide nucleic acid fluorescent in situ hybridization (PNA-FISH) with confocal microscopy to visualize and confirm the presence of biofilms. RESULTS: In 19 of 20 (95%) studied patients presenting with DFO, it was associated with an infected diabetic foot ulcer. By DNA sequencing of infected bone, Corynebacterium sp. was the most commonly identified microorganism, followed by Finegoldia sp., Staphylococcus sp., Streptococcus sp., Porphyromonas sp., and Anaerococcus sp. Six of 20 bone samples (30%) contained only one or two pathogens, while the remaining 14 (70%) had polymicrobial communities. Using a combination of SEM and PNA-FISH, we identified microbial aggregates in biofilms in 16 (80%) bone specimens and found that they were typically coccoid or rod-shaped aggregates. CONCLUSIONS: The presence of biofilms in DFO may explain why non-surgical treatment of DFO, relying on systemic antibiotic therapy, may not resolve some chronic infections caused by biofilm-producing strains.

Prognosis of the infected diabetic foot ulcer: a 12-month prospective observational study.

AIMS: To determine clinical outcomes and explore prognostic factors related to ulcer healing in people with a clinically infected diabetic foot ulcer. METHODS: This multicentre, prospective, observational study reviewed participants' data at 12 months after culture of a diabetic foot ulcer requiring antibiotic therapy. From participants' notes, we obtained information on the incidence of wound healing, ulcer recurrence, lower extremity amputation, lower extremity revascularization and death. We estimated the cumulative incidence of healing at 6 and 12 months, adjusted for lower extremity amputation and death using a competing risk analysis, and explored the relationship between baseline factors and healing incidence. RESULTS: In the first year after culture of the index ulcer, 45/299 participants (15.1%) had died. The ulcer had healed in 136 participants (45.5%), but recurred in 13 (9.6%). An ipsilateral lower extremity amputation was recorded in 52 (17.4%) and revascularization surgery in 18 participants (6.0%). Participants with an ulcer present for ~2 months or more had a lower incidence of healing (hazard ratio 0.55, 95% CI 0.39 to 0.77), as did those with a PEDIS (perfusion, extent, depth, infection, sensation) perfusion grade of ≥2 (hazard ratio 0.37, 95% CI 0.25 to 0.55). Participants with a single ulcer on their index foot had a higher incidence of healing than those with multiple ulcers (hazard ratio 1.90, 95% CI 1.18 to 3.06). CONCLUSIONS: Clinical outcomes at 12 months for people with an infected diabetic foot ulcer are generally poor. Our data confirm the adverse prognostic effect of limb ischaemia, longer ulcer duration and the presence of multiple ulcers.

Prevention and management of foot problems in diabetes: A Summary Guidance for Daily Practice 2015, based on the IWGDF guidance documents.

Foot problems complicating diabetes are a source of major patient suffering and societal costs. To prevent, or at least reduce, the adverse effects of foot problems in diabetes, the International Working Group on the Diabetic Foot (IWGDF; www.iwgdf.org) was founded in 1996, consisting of experts from almost all the disciplines involved in the care of patients with diabetes and foot problems. An important output of the IWGDF is the international consensus guidance, continuously updated since 1999. To date, the publications have been translated into 26 languages, and more than 100,000 copies have been distributed globally. The "Summary Guidance for Daily Practice" summarises the essentials of prevention and management of foot problems in persons with diabetes for clinicians who work with these patients on a daily basis. This guidance is the result of a long and careful process that started with the empaneling in 2013 of five working groups consisting of 49 international experts. These experts performed seven targeted systematic reviews to provide the evidence supporting the five chapters of the IWGDF Guidance on prevention; footwear and offloading; diagnosis, prognosis and management of peripheral artery disease; diagnosis and management of foot infections; interventions to enhance healing. In total almost 80,000 studies were detected by our literature review. After review of the title and abstract the reviewers of the different working groups selected only studies that fulfilled a minimal set of quality criteria and ended up with 429 articles for complete quality analysis. The GRADE system was used to translate the evidence from the studies into recommendations for daily clinical practice. The rating of each recommendation takes into account both the strength and the quality of the evidence. The IWGDF Guidance 2015 makes a total of 77 recommendations on prevention and management of foot problems in diabetes. These recommendations were condensed by the editorial board into this "Summary Guidance". Encouraging and aiding clinicians to follow the evidence-based recommendations of the IWGDF Guidance 2015, and in particular the principles outlined in the "Summary Guidance", will likely result in a worldwide reduction in, and better outcomes of, foot problems in persons with diabetes, helping to reduce the morbidity and mortality associated with this major health problem.

The 2015 IWGDF guidance documents on prevention and management of foot problems in diabetes: development of an evidence-based global consensus.

Foot problems complicating diabetes are a source of major patient suffering and societal costs. Investing in evidence-based, internationally appropriate diabetic foot care guidance is likely among the most cost-effective forms of healthcare expenditure, provided it is goal-focused and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has been publishing and updating international Practical Guidelines since 1999. The 2015 updates are based on systematic reviews of the literature, and recommendations are formulated using the Grading of Recommendations Assessment Development and Evaluation system. As such, we changed the name from 'Practical Guidelines' to 'Guidance'. In this article we describe the development of the 2015 IWGDF Guidance documents on prevention and management of foot problems in diabetes. This Guidance consists of five documents, prepared by five working groups of international experts. These documents provide guidance related to foot complications in persons with diabetes on: prevention; footwear and offloading; peripheral artery disease; infections; and, wound healing interventions. Based on these five documents, the IWGDF Editorial Board produced a summary guidance for daily practice. The resultant of this process, after reviewed by the Editorial Board and by international IWGDF members of all documents, is an evidence-based global consensus on prevention and management of foot problems in diabetes. Plans are already under way to implement this Guidance. We believe that following the recommendations of the 2015 IWGDF Guidance will almost certainly result in improved management of foot problems in persons with diabetes and a subsequent worldwide reduction in the tragedies caused by these foot problems.

Interventions in the management of infection in the foot in diabetes: a systematic review.

The expert panel on diabetic foot infection (DFI) of the International Working Group on the Diabetic Foot conducted a systematic review seeking all published reports relating to any type of treatment for infection of the foot in persons with diabetes published as of 30 June 2014. This review, conducted with both PubMed and EMBASE, was used to update an earlier one undertaken on 30 June 2010 using the same search string. Eligible publications included those that had outcome measures reported for both a treated and a control population that were managed either at the same time, or as part of a before-and-after case design. We did not include studies that contained only information related to definition or diagnosis, but not treatment, of DFI. The current search identified just seven new articles meeting our criteria that were published since the 33 identified with the previous search, making a total of 40 articles from the world literature. The identified articles included 37 randomised controlled trials (RCTs) and three cohort studies with concurrent controls, and included studies on the use of surgical procedures, topical antiseptics, negative pressure wound therapy and hyperbaric oxygen. Among the studies were 15 RCTs that compared outcomes of treatment with new antibiotic preparations compared with a conventional therapy in the management of skin and soft tissue infection. In addition, 10 RCTs and 1 cohort study compared different treatments for osteomyelitis in the diabetic foot. Results of comparisons of different antibiotic regimens generally demonstrated that newly introduced antibiotic regimens appeared to be as effective as conventional therapy (and also more cost-effective in one study), but one study failed to demonstrate non-inferiority of a new antibiotic compared with that of a standard agent. Overall, the available literature was both limited in both the number of studies and the quality of their design. Thus, our systematic review revealed little evidence upon which to make recommendations for treatment of DFIs. There is a great need for further well-designed trials that will provide robust data upon which to make decisions about the most appropriate treatment of both skin and soft tissue infection and osteomyelitis in diabetic patients.

Prevention and management of foot problems in diabetes: a Summary Guidance for Daily Practice 2015, based on the IWGDF Guidance Documents.

In this 'Summary Guidance for Daily Practice', we describe the basic principles of prevention and management of foot problems in persons with diabetes. This summary is based on the International Working Group on the Diabetic Foot (IWGDF) Guidance 2015. There are five key elements that underpin prevention of foot problems: (1) identification of the at-risk foot; (2) regular inspection and examination of the at-risk foot; (3) education of patient, family and healthcare providers; (4) routine wearing of appropriate footwear; and (5) treatment of pre-ulcerative signs. Healthcare providers should follow a standardized and consistent strategy for evaluating a foot wound, as this will guide further evaluation and therapy. The following items must be addressed: type, cause, site and depth, and signs of infection. There are seven key elements that underpin ulcer treatment: (1) relief of pressure and protection of the ulcer; (2) restoration of skin perfusion; (3) treatment of infection; (4) metabolic control and treatment of co-morbidity; (5) local wound care; (6) education for patient and relatives; and (7) prevention of recurrence. Finally, successful efforts to prevent and manage foot problems in diabetes depend upon a well-organized team, using a holistic approach in which the ulcer is seen as a sign of multi-organ disease, and integrating the various disciplines involved.

KPC-producing Klebsiella pneumoniae rectal colonization is a risk factor for mortality in patients with diabetic foot infections.

To evaluate the relationship between carbapenemase-producing Klebsiella pneumoniae (KPC-Kp) gut colonization and mortality in diabetic patients with a foot infection (DFI) we performed a single-centre, retrospective, matched case-control study. In the study period, we identified 21 patients with DFI who had KPC-Kp gut colonization and 21 controls. The 90-day mortality rate was significantly higher in patients with colonized guts (47%) than the controls (4%) (p 0.013). A multivariate analysis demonstrated that gut colonization with KPC-Kp was the only independent predictor of mortality: odds ratio 13.33, 95% CI 1.90-272.80, p 0.024. In patients with DFI, KPC-Kp gut colonization appears to be an important risk factor for mortality.

Challenges in diagnosing infection in the diabetic foot.

Diagnosing the presence of infection in the foot of a patient with diabetes can sometimes be a difficult task. Because open wounds are always colonized with microorganisms, most agree that infection should be diagnosed by the presence of systemic or local signs of inflammation. Determining whether or not infection is present in bone can be especially difficult. Diagnosis begins with a history and physical examination in which both classic and 'secondary' findings suggesting invasion of microorganisms or a host response are sought. Serological tests may be helpful, especially measurement of the erythrocyte sedimentation rate in osteomyelitis, but all (including bone biomarkers and procalcitonin) are relatively non-specific. Cultures of properly obtained soft tissue and bone specimens can diagnose and define the causative pathogens in diabetic foot infections. Newer molecular microbial techniques, which may not only identify more organisms but also virulence factors and antibiotic resistance, look very promising. Imaging tests generally begin with plain X-rays; when these are inconclusive or when more detail of bone or soft tissue abnormalities is required, more advanced studies are needed. Among these, magnetic resonance imaging is generally superior to standard radionuclide studies, but newer hybrid imaging techniques (single-photon emission computed tomography/computed tomography, positron emission tomography/computed tomography and positron emission tomography/magnetic resonance imaging) look to be useful techniques, and new radiopharmaceuticals are on the horizon. In some cases, ultrasonography, photographic and thermographic methods may also be diagnostically useful. Improved methods developed and tested over the past decade have clearly increased our accuracy in diagnosing diabetic foot infections.

Managing diabetic foot infections: a review of the new guidelines.

Foot infections are amongst the most frequent and severe complications linked to diabetes mellitus and are the most common non-traumatic cause of lower limb amputation. Appropriate management of these infections, however, can improve their outcome. The Infectious Diseases Society of America (IDSA) constituted a panel of multidisciplinary experts in 2004 to develop guidelines for the diagnosis and treatment of diabetic foot infections, which have been widely used and validated. Because there have been many new publications in the field, and the IDSA updated the format for all guidelines, they asked the diabetic foot infection committee to revise the 2004 publication. The revised guidelines, based on a thorough and systematic review of the literature, were published in 2012. They are built around 10 key questions concerning diagnosis and treatment; these are answered, with a summary of the evidence provided, and given a GRADE rating for the strength of the recommendation and quality of the evidence. The updated guidelines also include advice on implementing these recommendations, suggestions for regulatory changes to enhance care for diabetic foot infections, recommendations on performance measures and suggested areas for future research. They also include 14 tables, 1 figure, and 345 references, most of which were published after the first guidelines in 2004. Implementing these guidelines should improve outcomes in patients with a DFI.

Gas gangrene in the diabetic foot: lessons learned from a salvaged limb.

A 55 year old man was seen in the emergency department with an infected right foot and sepsis. Examination of the right foot revealed subcutaneous crepitus from the metatarsal head up to the tarsus; interstitial and intramedullary gas was confirmed on x-rays and computed tomographic scans. During 44 days of hospitalization, the patient was treated with multiple courses of antibiotic therapy, various wound care modalities (including negative wound pressure therapy) and several surgical interventions (debridements, amputations, revascularizations and reconstructive plastic surgery). Although limb salvage was ultimately accomplished, in retrospect many management decisions were suboptimal. A critical reassessment of our approach to this patient allowed us to identify several areas for improvement and this audit provided us an opportunity to learn from managing this difficult case.

Inappropriate initial antibiotic treatment for complicated skin and soft tissue infections in hospitalized patients: incidence and associated factors.

We analyzed 525 hospitalized adults treated with intravenous antibiotic(s) for complicated skin and soft tissue infections (cSSTIs) to assess incidence of, and risk factors associated with, inappropriate initial antibiotic treatment (IIAT). IIAT was given to 22.5% of enrolled patients. The rate of IIAT did not vary by type of facility (academic versus community) but was significantly higher in rural than urban hospitals (38.9% versus 21.3%, P = 0.02). Pathogens were exclusively gram-positive in 68% of patients, exclusively gram-negative in 13%, and mixed in 19%. Staphylococcus aureus was the most frequently isolated pathogen (in 65%), 54% of which were methicillin-resistant. Significant independent risk factors for IIAT were: admission to a rural hospital (odds ratio = 2.34; 95% confidence interval: 1.06-5.19), dialysis treatment (3.86; 1.15-12.93), cancer other than non-melanoma skin cancer (5.23; 1.78-15.36), and infection with gram-negative (3.43; 1.79-6.60) or mixed (4.52; 2.62-7.78) pathogens. IIAT for cSSTIs was relatively frequent in these hospitalized patients, especially those with selected risk factors.

Economic outcomes of inappropriate initial antibiotic treatment for complicated skin and soft tissue infections: a multicenter prospective observational study.

This study examined economic outcomes associated with inappropriate initial antibiotic treatment (IIAT) in complicated skin and soft tissue infections using data from adults hospitalized and treated with intravenous antibiotic therapy. We specifically analyzed for the subsets of patients infected with methicillin-resistant Staphylococcus aureus (MRSA), with healthcare-associated (HCA) infections, or both. Data from 494 patients (HCA: 360; MRSA:175; MRSA + HCA: 129) showed the overall mean length of stay (LOS) was 7.4 days and 15.0% had the composite economic outcome of any subsequent hospital admissions, emergency department visits, or unscheduled visits related to the study infection. A total of 23.1% of patients had IIAT; after adjustments, these patients had longer LOS than patients without IIAT in the HCA cohort (marginal LOS = 1.39 days, P = 0.03) and the MRSA + HCA cohort (marginal LOS = 2.43 days, P = 0.01) and were significantly more likely to have the composite economic outcome in all study cohorts (odds ratio: overall = 1.79; HCA = 3.09; MRSA = 3.66; MRSA + HCA = 6.92; all P < 0.05).

The microbiologic profile of diabetic foot infections in Turkey: a 20-year systematic review: diabetic foot infections in Turkey.

The causative pathogens in diabetic foot infections differ in studies of European compared with Asian populations. The purpose of this study was to determine the causative microorganisms and their antibiotic sensitivity patterns in diabetic patients with a foot infection in Turkey, a country at the crossroads of these two continents. We performed a comprehensive literature search to identify all published studies pertaining to DFIs in patients cared for in Turkey. To assess changes in causative organisms and their antibiotic sensitivity patterns over time, we compared the results of just the most recent 5 years (2007-2011) with those of the past 20-years (1989-2011). We identified 31 studies meeting our inclusion criteria. Overall, these studies reported 2,097 patients, from whom 1,974 microorganisms were isolated. The total percentage of gram-negative and gram-positive aerobic bacteria were similar in each of the assessed periods. The rate of isolation of Staphylococcus aureus during the entire period, compared with just the past 5 years, was 23.8% and 19.1%, respectively, while the rate of methicillin-resistant S. aureus was 7.8% and 5.7%, respectively. The isolation rate of Pseudomonas aeruginosa was 13.7% for the entire period and 14.9% for the past 5 years. While linezolid, vancomycin and teicoplanin were the most active agents against gram-positive microorganisms, imipenem and cefoperazone-sulbactam were the most active against gram-negative microorganisms. This systematic review demonstrated few substantial changes in diabetic foot microbiology over the past 20 years. The data may help develop and update local clinical guidelines regarding antibiotic therapy for diabetic foot infections in Turkey. Further studies, especially with optimal culture methods, would be useful to validate these findings.

Diabetic foot infections: state-of-the-art.

Foot infections are frequent and potentially devastating complications of diabetes. Unchecked, infection can progress contiguously to involve the deeper soft tissues and ultimately the bone. Foot ulcers in people with diabetes are most often the consequence of one or more of the following: peripheral sensory neuropathy, motor neuropathy and gait disorders, peripheral arterial insufficiency or immunological impairments. Infection develops in over half of foot ulcers and is the factor that most often leads to lower extremity amputation. These amputations are associated with substantial morbidity, reduced quality of life and major financial costs. Most infections can be successfully treated with optimal wound care, antibiotic therapy and surgical procedures. Employing evidence-based guidelines, multidisciplinary teams and institution-specific clinical pathways provides the best approach to guide clinicians through this multifaceted problem. All clinicians regularly seeing people with diabetes should have an understanding of how to prevent, diagnose and treat foot infections, which requires familiarity with the pathophysiology of the problem and the literature supporting currently recommended care.

Diagnosing diabetic foot infection: the role of imaging and a proposed flow chart for assessment.

Diabetes mellitus, a major current epidemic, is frequently complicated by foot infections that are associated with high morbidity. Diagnosing these infections, especially whether or not underlying bone is involved, poses clinical challenges, but is crucial to making proper decisions regarding therapeutic strategies. The most effective means of managing patients with a diabetic foot infection is within the framework of a multidisciplinary team. Present diagnostic efforts are aimed at developing better methods to differentiate uninfected from infected soft tissue wounds, to determine when bone infection is present, and to more clearly define when infection has resolved with treatment. Imaging studies play a major role in diagnosis. This usually begins with plain radiographs, but when advanced imaging is needed, magnetic resonance imaging (MRI) is considered the modality of choice. Newer techniques, such as molecular hybrid imaging, positron emission tomography (PET)/computed tomography (CT) and single photon emission (SPECT)/CT using various radiotracers, play an increasing role. These tests may redefine the non-invasive diagnostic work-up of diabetic foot wounds, potentially leading to substantial improvements in patient management. As experts in infectious diseases, radiology and nuclear medicine, we reviewed the available literature on diagnosing diabetic foot infections, especially the currently available imaging techniques, and developed a proposed diagnostic flow chart, for evaluating patients with a diabetic foot wound.

A systematic review of the effectiveness of interventions in the management of infection in the diabetic foot.

The International Working Group on the Diabetic Foot expert panel on infection conducted a systematic review of the published evidence relating to treatment of foot infection in diabetes. Our search of the literature published prior to August 2010 identified 7517 articles, 29 of which fulfilled predefined criteria for detailed data extraction. Four additional eligible papers were identified from other sources. Of the total of 33 studies, 29 were randomized controlled trials, and four were cohort studies. Among 12 studies comparing different antibiotic regimens in the management of skin and soft-tissue infection, none reported a better response with any particular regimen. Of seven studies that compared antibiotic regimens in patients with infection involving both soft tissue and bone, one reported a better clinical outcome in those treated with cefoxitin compared with ampicillin/sulbactam, but the others reported no differences between treatment regimens. In two health economic analyses, there was a small saving using one regimen versus another. No published data support the superiority of any particular route of delivery of systemic antibiotics or clarify the optimal duration of antibiotic therapy in either soft-tissue infection or osteomyelitis. In one non-randomized cohort study, the outcome of treatment of osteomyelitis was better when the antibiotic choice was based on culture of bone specimens as opposed to wound swabs, but this study was not randomized, and the results may have been affected by confounding factors. Results from two studies suggested that early surgical intervention was associated with a significant reduction in major amputation, but the methodological quality of both was low. In two studies, the use of superoxidized water was associated with a better outcome than soap or povidone iodine, but both had a high risk of bias. Studies using granulocyte-colony stimulating factor reported mixed results. There was no improvement in infection outcomes associated with hyperbaric oxygen therapy. No benefit has been reported with any other intervention, and, overall, there are currently no trial data to justify the adoption of any particular therapeutic approach in diabetic patients with infection of either soft tissue or bone of the foot.

Expert opinion on the management of infections in the diabetic foot.

This update of the International Working Group on the Diabetic Foot incorporates some information from a related review of diabetic foot osteomyelitis (DFO) and a systematic review of the management of infection of the diabetic foot. The pathophysiology of these infections is now well understood, and there is a validated system for classifying the severity of infections based on their clinical findings. Diagnosing osteomyelitis remains difficult, but several recent publications have clarified the role of clinical, laboratory and imaging tests. Magnetic resonance imaging has emerged as the most accurate means of diagnosing bone infection, but bone biopsy for culture and histopathology remains the criterion standard. Determining the organisms responsible for a diabetic foot infection via culture of appropriately collected tissue specimens enables clinicians to make optimal antibiotic choices based on culture and sensitivity results. In addition to culture-directed antibiotic therapy, most infections require some surgical intervention, ranging from minor debridement to major resection, amputation or revascularization. Clinicians must also provide proper wound care to ensure healing of the wound. Various adjunctive therapies may benefit some patients, but the data supporting them are weak. If properly treated, most diabetic foot infections can be cured. Providers practising in developing countries, and their patients, face especially challenging situations.

Skin and soft tissue infections in hospitalised patients with diabetes: culture isolates and risk factors associated with mortality, length of stay and cost.

AIMS/HYPOTHESIS: Skin and soft tissue infections (SSTIs) cause substantial morbidity in persons with diabetes. There are few data on pathogens or risk factors associated with important outcomes in diabetic patients hospitalised with SSTIs. METHODS: Using a clinical research database from CareFusion, we identified 3,030 hospitalised diabetic patients with positive culture isolates and a diagnosis of SSTI in 97 US hospitals between 2003 and 2007. We classified the culture isolates and analysed their association with the anatomic location of infection, mortality, length of stay and hospital costs. RESULTS: The only culture isolate with a significantly increased prevalence was methicillin-resistant Staphylococcus aureus (MRSA); prevalence for infection of the foot was increased from 11.6 to 21.9% (p < 0.0001) and for non-foot locations from 14.0% to 24.6% (p = 0.006). Patients with non-foot (vs foot) infections were more severely ill at presentation and had higher mortality rates (2.2% vs 1.0%, p < 0.05). Significant independent risk factors associated with higher mortality rates included having a polymicrobial culture with Pseudomonas aeruginosa (OR 3.1), a monomicrobial culture with other gram-negatives (OR 8.9), greater illness severity (OR 1.9) and being transferred from another hospital (OR 5.1). These factors and need for major surgery were also independently associated with longer length of stay and higher costs. CONCLUSIONS/INTERPRETATION: Among diabetic patients hospitalised with SSTI from 2003 to 2007, only MRSA increased in prevalence. Patients with non-foot (vs foot) infections were more severely ill. Independent risk factors for increased mortality rates, length of stay and costs included more severe illness, transfer from another hospital and wound cultures with Pseudomonas or other gram-negatives.

Pharmacotherapy of diabetic foot osteomyelitis.

Diabetic foot osteomyelitis (DFO) complicates about 20% of diabetic foot infections (DFIs) and increases the risk of lower extremity amputation. This contentious infection is important to discuss, given the frequency with which diabetes mellitus and its complications occur and the devastating consequences of amputation. The diagnosis and management of DFO is complicated by the diverse presentations, delayed recognition, poorly defined diagnostic criteria, and lack of validated treatment regimens. Major issues of concern include when to undertake bone resection surgery and which antimicrobial agents to use, by what route, and for how long. Patients in whom DFO is suspected are best cared for by a multidisciplinary team, including infectious disease physicians or clinical microbiologists, orthopaedic, plastic and vascular surgeons, diabetologists, primary care physicians, podiatrists and specialist (especially tissue viability) nurses. Such multidisciplinary teams have repeatedly been shown to improve disease outcomes. We herein analyse the limited, and recently published, literature on the pharmacotherapy of DFO and put it into the broader context of management of DFI and osteomyelitis.