Diagnostic imaging of the diabetic foot: an EANM evidence-based guidance.

PURPOSE: Consensus on the choice of the most accurate imaging strategy in diabetic foot infective and non-infective complications is still lacking. This document provides evidence-based recommendations, aiming at defining which imaging modality should be preferred in different clinical settings. METHODS: This working group includes 8 nuclear medicine physicians appointed by the European Association of Nuclear Medicine (EANM), 3 radiologists and 3 clinicians (one diabetologist, one podiatrist and one infectious diseases specialist) selected for their expertise in diabetic foot. The latter members formulated some clinical questions that are not completely covered by current guidelines. These questions were converted into statements and addressed through a systematic analysis of available literature by using the PICO (Population/Problem-Intervention/Indicator-Comparator-Outcome) strategy. Each consensus statement was scored for level of evidence and for recommendation grade, according to the Oxford Centre for Evidence-Based Medicine (OCEBM) criteria. RESULTS: Nine clinical questions were formulated by clinicians and used to provide 7 evidence-based recommendations: (1) A patient with a positive probe-to-bone test, positive plain X-rays and elevated ESR should be treated for presumptive osteomyelitis (OM). (2) Advanced imaging with MRI and WBC scintigraphy, or [18F]FDG PET/CT, should be considered when it is needed to better evaluate the location, extent or severity of the infection, in order to plan more tailored treatment. (3) In a patient with suspected OM, positive PTB test but negative plain X-rays, advanced imaging with MRI or WBC scintigraphy + SPECT/CT, or with [18F]FDG PET/CT, is needed to accurately assess the extent of the infection. (4) There are no evidence-based data to definitively prefer one imaging modality over the others for detecting OM or STI in fore- mid- and hind-foot. MRI is generally the first advanced imaging modality to be performed. In case of equivocal results, radiolabelled WBC imaging or [18F]FDG PET/CT should be used to detect OM or STI. (5) MRI is the method of choice for diagnosing or excluding Charcot neuro-osteoarthropathy; [18F]FDG PET/CT can be used as an alternative. (6) If assessing whether a patient with a Charcot foot has a superimposed infection, however, WBC scintigraphy may be more accurate than [18F]FDG PET/CT in differentiating OM from Charcot arthropathy. (7) Whenever possible, microbiological or histological assessment should be performed to confirm the diagnosis. (8) Consider appealing to an additional imaging modality in a patient with persisting clinical suspicion of infection, but negative imaging. CONCLUSION: These practical recommendations highlight, and should assist clinicians in understanding, the role of imaging in the diagnostic workup of diabetic foot complications.

Topical pravibismane as adjunctive therapy for moderate or severe diabetic foot infections: A phase 1b randomized, multicenter, double-blind, placebo-controlled trial.

This Phase 1b study was designed to evaluate the safety and efficacy of pravibismane, a novel broad-spectrum topical anti-infective, in managing moderate or severe chronic diabetic foot ulcer (DFU) infections. This randomized, double-blind, placebo-controlled, multicenter study consisted of 39 individuals undergoing pravibismane treatment and 13 individuals in the placebo group. Assessment of safety parameters included clinical observations of tolerability and pharmacokinetics from whole blood samples. Pravibismane was well-tolerated and exhibited minimal systemic absorption, as confirmed by blood concentrations that were below the lower limit of quantitation (0.5 ng/mL) or in the low nanomolar range, which is orders of magnitude below the threshold of pharmacological relevance for pravibismane. Pravibismane treated subjects showed approximately 3-fold decrease in ulcer size compared to the placebo group (85% vs. 30%, p = 0.27). Furthermore, the incidence of ulcer-related lower limb amputations was approximately 6-fold lower (2.6%) in the pooled pravibismane group versus 15.4% in the placebo group (p = 0.15). There were no treatment emergent or serious adverse events related to study drug. The initial findings indicate that topical pravibismane was safe and potentially effective treatment for improving recovery from infected chronic ulcers by reducing ulcer size and facilitating wound healing in infected DFUs (ClinicalTrials.gov Identifier NCT02723539).

Initial antibiotic therapy for postoperative moderate or severe diabetic foot infections: Broad versus narrow spectrum, empirical versus targeted.

AIM: To retrospectively evaluate clinical and microbiological outcomes after combined surgical and medical therapy for diabetic foot infections (DFIs), stratifying between the empirical versus the targeted nature, and between an empirical broad versus a narrow-spectrum, antibiotic therapy. METHODS: We retrospectively assessed the rate of ultimate therapeutic failures for each of three types of initial postoperative antibiotic therapy: adequate empirical therapy; culture-guided therapy; and empirical inadequate therapy with a switch to targeted treatment based on available microbiological results. RESULTS: We included data from 332 patients who underwent 716 DFI episodes of surgical debridement, including partial amputations. Clinical failure occurred in 40 of 194 (20.6%) episodes where adequate empirical therapy was given, in 77 of 291 (26.5%) episodes using culture-guided (and correct) therapy from the start, and in 73 of 231 (31.6%) episodes with switching from empirical inadequate therapy to culture-targeted therapy. Equally, a broad-spectrum antibiotic choice could not alter this failure risk. Group comparisons, Kaplan-Meier curves and Cox regression analyses failed to show either statistical superiority or inferiority of any of the initial antibiotic strategies. CONCLUSIONS: In this study, the microbiological adequacy of the initial antibiotic regimen after (surgical) debridement for DFI did not alter therapeutic outcomes. We recommend that clinicians follow the stewardship approach of avoiding antibiotic de-escalation and start with a narrow-spectrum regimen based on the local epidemiology.

Moderate to Severe Soft Tissue Diabetic Foot Infections: A Randomized, Controlled, Pilot Trial of Post-debridement Antibiotic Treatment for 10 versus 20 days.

BACKGROUND: The optimal duration of antibiotic therapy for soft-tissue infections of the diabetic foot remains unknown. OBJECTIVE: We determine if antibiotic therapy after debridement for a short (10 days), compared with a long (20 days), duration for soft-tissue infections of the diabetic foot results in similar rates of clinical remission and adverse events (AE). SUMMARY OF BACKGROUND DATA: The optimal duration of systemic antibiotic therapy, after successful debridement, for soft tissue infections of diabetic patients is unknown. Because of the high recurrence risk, overuse is commonplace. METHODS: This was a randomized, controlled, non-inferiority pilot trial of cases of diabetic foot infection (excluding osteomyelitis) with the primary outcome of "clinical remission at 2-months follow-up". RESULTS: Among 66 enrolled episodes (17% females; median age 71 years), we randomized 35 to the 10-day arm and 31 to the 20-day arm. The median duration of the parenteral antibiotic therapy was 1 day, with the remainder given orally. In the intention-to-treat population, we achieved clinical remission in 27 (77%) patients in the 10-day arm compared to 22 (71%) in the 20-days arm ( P = 0.57). There were a similar proportion in each arm of AE (14/35 versus 11/31; P = 0.71), and remission in the per-protocol population (25/32 vs 18/27; P = 0.32). Overall, 8 soft tissue DFIs in the 10-day arm and 5 cases in the 20-day arm recurred as a new osteomyelitis [8/35 (23%) versus 5/31 (16%); P = 0.53]. Overall, the number of recurrences limited to the soft tissues was 4 (6%). By multivariate analysis, rates of remission (intention-to-treat population, hazard ratio 0.6, 95%CI 0.3-1.1; per-protocol population 0.8, 95%CI 0.4-1.5) and AE were not significantly different with a 10-day compared to 20-day course. CONCLUSIONS: In this randomized, controlled pilot trial, post-debridement antibiotic therapy for soft tissue DFI for 10 days gave similar (and non-inferior) rates of remission and AEs to 20 days. A larger confirmatory trial is under way. TRIAL REGISTRATION: ClinicalTrials NCT03615807.

Oral versus Intravenous Antibiotics for Bone and Joint Infection.

BACKGROUND: The management of complex orthopedic infections usually includes a prolonged course of intravenous antibiotic agents. We investigated whether oral antibiotic therapy is noninferior to intravenous antibiotic therapy for this indication. METHODS: We enrolled adults who were being treated for bone or joint infection at 26 U.K. centers. Within 7 days after surgery (or, if the infection was being managed without surgery, within 7 days after the start of antibiotic treatment), participants were randomly assigned to receive either intravenous or oral antibiotics to complete the first 6 weeks of therapy. Follow-on oral antibiotics were permitted in both groups. The primary end point was definitive treatment failure within 1 year after randomization. In the analysis of the risk of the primary end point, the noninferiority margin was 7.5 percentage points. RESULTS: Among the 1054 participants (527 in each group), end-point data were available for 1015 (96.3%). Treatment failure occurred in 74 of 506 participants (14.6%) in the intravenous group and 67 of 509 participants (13.2%) in the oral group. Missing end-point data (39 participants, 3.7%) were imputed. The intention-to-treat analysis showed a difference in the risk of definitive treatment failure (oral group vs. intravenous group) of -1.4 percentage points (90% confidence interval [CI], -4.9 to 2.2; 95% CI, -5.6 to 2.9), indicating noninferiority. Complete-case, per-protocol, and sensitivity analyses supported this result. The between-group difference in the incidence of serious adverse events was not significant (146 of 527 participants [27.7%] in the intravenous group and 138 of 527 [26.2%] in the oral group; P=0.58). Catheter complications, analyzed as a secondary end point, were more common in the intravenous group (9.4% vs. 1.0%). CONCLUSIONS: Oral antibiotic therapy was noninferior to intravenous antibiotic therapy when used during the first 6 weeks for complex orthopedic infection, as assessed by treatment failure at 1 year. (Funded by the National Institute for Health Research; OVIVA Current Controlled Trials number, ISRCTN91566927 .).

Three Weeks Versus Six Weeks of Antibiotic Therapy for Diabetic Foot Osteomyelitis: A Prospective, Randomized, Noninferiority Pilot Trial.

BACKGROUND: In patients with diabetic foot osteomyelitis (DFO) who underwent surgical debridement, we investigated whether a short (3 weeks) duration compared with a long (6 weeks) duration of systemic antibiotic treatment is associated with noninferior results for clinical remission and adverse events (AEs). METHODS: In this prospective, randomized, noninferiority pilot trial, we randomized (allocation 1:1) patients with DFO after surgical debridement to either a 3-week or a 6-week course of antibiotic therapy. The minimal duration of follow-up after the end of therapy was 2 months. We compared outcomes using Cox regression and noninferiority analyses (25% margin, power 80%). RESULTS: Among 93 enrolled patients (18% females; median age 65 years), 44 were randomized to the 3-week arm and 49 to the 6-week arm. The median number of surgical debridements was 1 (range, 0-2 interventions). In the intention-to-treat (ITT) population, remission occurred in 37 (84%) of the patients in the 3-week arm compared with 36 (73%) in the 6-week arm (P = .21). The number of AEs was similar in the 2 study arms (17/44 vs 16/49; P = .51), as were the remission incidences in the per-protocol (PP) population (33/39 vs 32/43; P = .26). In multivariate analysis, treatment with the shorter antibiotic course was not significantly associated with remission (ITT population: hazard ratio [HR], 1.1 [95% confidence interval {CI}, .6-1.7]; PP population: HR, 0.8 [95% CI: .5-1.4]). CONCLUSIONS: In this randomized controlled pilot trial, a postdebridement systemic antibiotic therapy course for DFO of 3 weeks gave similar (and statistically noninferior) incidences of remission and AE to a course of 6 weeks. CLINICAL TRIALS REGISTRATION: NCT03615807; BASEC 2016-01008 (Switzerland).

Is routine measurement of the serum C-reactive protein level helpful during antibiotic therapy for diabetic foot infection?

Clinicians frequently monitor serum C-reactive protein (CRP) levels during therapy for diabetic foot infections (DFIs), but evidence supporting this is unclear. Using a database from prospective controlled DFI trials, with fixed duration of antibiotic therapy, we correlated the CRP levels at study enrolment and at end of therapy (EOT). Among 159 DFI episodes, 93 involved the bone and 66 the soft tissues. Overall, treatment cured 122 infections (77%), while 37 episodes (23%) recurred after a median of 53 days. The median CRP in the groups with cure versus failure differed minimally at enrolment (median 67 vs. 81 mg/L) or EOT (7 vs. 10 mg/L). Similarly, there was negligible difference in the percentage of CRP levels that normalized at EOT (39% vs. 35%). In our prospective cohorts, a blunt iterative monitoring of CRP during DFI treatment, without correlation with clinical findings, failed to predict treatment failures.

Treating Diabetic Foot Osteomyelitis: A Practical State-of-the-Art Update.

Background and Objectives: Diabetic foot osteomyelitis (DFO) can be difficult to treat and securing optimal clinical outcomes requires a multidisciplinary approach involving a wide variety of medical, surgical and other health care professionals, as well as the patient. Results of studies conducted in the past few years have allowed experts to formulate guidelines that can improve clinical outcomes. Material and Methods: We conducted a narrative review of the literature on treat- ment of DFO, with an emphasis on studies published in the last two years, especially regarding antimicrobial therapies and surgical approached to treatment of DFO, supplemented by our own extensive clinical and research experience in this field. Results: Major amputations were once com- mon for DFO but, with improved diagnostic and surgical techniques, "conservative" surgery (foot- sparing, resecting only the infected and necrotic bone) is becoming commonplace, especially for forefoot infections. Traditional antibiotic therapy, which has been administered predominantly in- travenously and frequently for several months, can often be replaced by appropriately selected oral antibiotic regimens following only a brief (or even no) parenteral therapy, and given for no more than 6 weeks. Based on ongoing studies, the recommended duration of treatment may soon be even shorter, especially for cases in which a substantial portion of the infected bone has been resected. Using the results of cultures (preferably of bone specimens) and antimicrobial stewardship princi- ples allows clinicians to select evidence-based antibiotic regimens, often of a limited pathogen spec- trum. Intra-osseous antimicrobial and surgical approaches to treatment are also evolving in light of ongoing research. Conclusions: In this narrative, evidenced-based review, taking consideration of principles of antimicrobial stewardship and good surgical practice, we have highlighted the recent literature and offered practical, state-of-the-art advice on the antibiotic and surgical management of DFO.

The dynamic wound microbiome.

BACKGROUND: Diabetic foot ulcers (DFUs) account for the majority of all limb amputations and hospitalizations due to diabetes complications. With 30 million cases of diabetes in the USA and 500,000 new diagnoses each year, DFUs are a growing health problem. Diabetes patients with limb amputations have high postoperative mortality, a high rate of secondary amputation, prolonged inpatient hospital stays, and a high incidence of re-hospitalization. DFU-associated amputations constitute a significant burden on healthcare resources that cost more than 10 billion dollars per year. Currently, there is no way to identify wounds that will heal versus those that will become severely infected and require amputation. MAIN BODY: Accurate identification of causative pathogens in diabetic foot ulcers is a critical component of effective treatment. Compared to traditional culture-based methods, advanced sequencing technologies provide more comprehensive and unbiased profiling on wound microbiome with a higher taxonomic resolution, as well as functional annotation such as virulence and antibiotic resistance. In this review, we summarize the latest developments in defining the microbiology of diabetic foot ulcers that have been unveiled by sequencing technologies and discuss both the future promises and current limitations of these approaches. In particular, we highlight the temporal patterns and system dynamics in the diabetic foot microbiome monitored and measured during wound progression and medical intervention, and explore the feasibility of molecular diagnostics in clinics. CONCLUSION: Molecular tests conducted during weekly office visits to clean and examine DFUs would allow clinicians to offer personalized treatment and antibiotic therapy. Personalized wound management could reduce healthcare costs, improve quality of life for patients, and recoup lost productivity that is important not only to the patient, but also to healthcare payers and providers. These efforts could also improve antibiotic stewardship and control the rise of "superbugs" vital to global health.

Diabetic foot disease: "The Times They are A Changin' ".

Diabetic foot disease greatly impacts both affected patients and society, but remains the "Cinderella" of diabetes-related complications. However, recent progress in research and guideline development have led to increased awareness of the problem and improved clinical outcomes. Thus, it is time for a shift in global perception of this increasingly prevalent problem. In this special issue, we present 7 up-to-date clinical guidelines and 10 systematic reviews developed by the International Working Group on the Diabetic Foot, together with 17 informative and stimulating related papers. These guidelines offer new recommendations on ulcer classification, diagnosis of infection severity, and vascular assessment, to assist in ulcer risk stratification, diagnosis and interdisciplinary communication. Key developments include providing guidance on methodological assessment of research papers; expanding the evidence base for ulcer treatment by the use of wound products and offloading treatment and suggestions for improving ulcer prevention through technological advances in patient monitoring of risk factors and footwear. The 17 invited papers discuss related topics ranging from stem cell research to patient psychology and describe the way forward in diabetic foot care. While there is much more to learn, the new knowledge of underlying pathways, advancements in diagnosis, treatment and prevention presented in this supplement should help improve outcomes and reduce the great and growing burden of diabetic foot disease.

Diagnosing diabetic foot osteomyelitis.

Bone involvement during an infection of the diabetic foot represents a serious complication associated with a high risk of amputation, prolonged antibiotic treatment and hospitalization. Diabetic foot osteomyelitis (DFOs) require a multidisciplinary approach given the usual complexity of these situations. DFO should be suspected in most cases especially in the most severe forms of soft tissue diabetic foot infections (DFIs) where the prevalence of bone infection may be up to 60%. Suspicion is based on clinical signs in particular a positive probe-to-bone (PTB) test, elevated inflammatory biomarkers especially erythrocyte sedimentation rate and abnormal imaging assessment using plain X-ray as a first-line choice. The combination of PTB test with plain X-ray has proven effective in the diagnosis of DFO. The confirmation (definite) diagnosis of DFO is based on the results of a bone sample examination obtained by either surgical or percutaneous biopsy. Sophisticated imaging examinations such as Magnetic Resonance Imaging (MRI) and nuclear imaging techniques are useful where doubt persists after first-line imaging assessment. These techniques may also help localize the bone infection site and increase the diagnostic performance of percutaneous bone biopsy. The quality of the microbiological documentation of DFO is likely to improve the adequacy of the antimicrobial therapy especially when medical (ie, no surgical resection of the infected bone tissues) is considered. The use of new (molecular) techniques for the identification of the bone pathogens have not yet proven superiority on classic cultural techniques for the management of such patients.

Practical Guidelines on the prevention and management of diabetic foot disease (IWGDF 2019 update).

Diabetic foot disease results in a major global burden for patients and the health care system. The International Working Group on the Diabetic Foot (IWGDF) has been producing evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. In 2019, all IWGDF Guidelines have been updated based on systematic reviews of the literature and formulation of recommendations by multidisciplinary experts from all over the world. In this document, the IWGDF Practical Guidelines, we describe the basic principles of prevention, classification, and treatment of diabetic foot disease, based on the six IWGDF Guideline chapters. We also describe the organizational levels to successfully prevent and treat diabetic foot disease according to these principles and provide addenda to assist with foot screening. The information in these practical guidelines is aimed at the global community of health care professionals who are involved in the care of persons with diabetes. Many studies around the world support our belief that implementing these prevention and management principles is associated with a decrease in the frequency of diabetes-related lower extremity amputations. We hope that these updated practical guidelines continue to serve as reference document to aid health care providers in reducing the global burden of diabetic foot disease.

Standards for the development and methodology of the 2019 International Working Group on the Diabetic Foot guidelines.

Diabetic foot disease is a source of major patient suffering and societal costs. Investing in evidence-based international guidelines on diabetic foot disease is likely among the most cost-effective forms of health care expenditure, provided the guidelines are outcome focused, evidence based, and properly implemented. The International Working Group on the Diabetic Foot (IWGDF) has published and updated international guidelines since 1999. The 2019 updates are based on formulating relevant clinical questions and outcomes, rigorous systematic reviews of the literature, and recommendations that are specific, and unambiguous along with their transparent rationale, all using the Grading of Recommendations Assessment Development and Evaluation (GRADE) framework. We herein describe the development of the 2019 IWGDF guidelines on the prevention and management of diabetic foot disease, which consists of six chapters, each prepared by a separate working group of international experts. These documents provide guidelines related to diabetic foot disease on prevention; offloading; peripheral artery disease; infection; wound healing interventions; and classification of diabetic foot ulcers. Based on these six chapters, the IWGDF Editorial Board also produced a set of practical guidelines. Each guideline underwent extensive review by the members of the IWGDF Editorial Board as well as independent international experts in each field. We believe that adoption and implementation of the 2019 IWGDF guidelines by health care providers, public health agencies, and policymakers will result in improved prevention and management of diabetic foot disease and a subsequent worldwide reduction in the patient and societal burden this disease causes.

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

The optimal approaches to managing diabetic foot infections remain a challenge for clinicians. Despite an exponential rise in publications investigating different treatment strategies, the various agents studied generally produce comparable results, and high-quality data are scarce. In this systematic review, we searched the medical literature using the PubMed and Embase databases for published studies on the treatment of diabetic foot infections as of June 2018. This systematic review is an update of previous reviews, the first of which was undertaken in 2010 and the most recent in 2014, by the infection committee of the International Working Group of the Diabetic Foot. We defined the context of literature by formulating clinical questions of interest, then developing structured clinical questions (PICOs) to address these. We only included data from controlled studies of an intervention to prevent or cure a diabetic foot infection. Two independent reviewers selected articles for inclusion and then assessed their relevant outcomes and the methodological quality. Our literature search identified a total of 15 327 articles, of which we selected 48 for full-text review; we added five more studies discovered by means other than the systematic literature search. Among these selected articles were 11 high-quality studies published in the last 4 years and two Cochrane systematic reviews. Overall, the outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetic foot were broadly equivalent across studies, except that treatment with tigecycline was inferior to ertapenem (±vancomycin). Similar outcomes were also reported in studies comparing primarily surgical and predominantly antibiotic treatment strategies in selected patients with diabetic foot osteomyelitis. There is insufficient high-quality evidence to assess the effect of various adjunctive therapies, such as negative pressure wound therapy, topical ointments or hyperbaric oxygen, on infection related outcomes of the diabetic foot. In general, the quality of more recent trial designs are better in past years, but there is still a great need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

Diagnosis of infection in the foot in diabetes: a systematic review.

BACKGROUND: Securing an early accurate diagnosis of diabetic foot infections and assessment of their severity are of paramount importance since these infections can cause great morbidity and potentially mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS: In June 2018, we searched the literature using PuEbMed and EMBASE for published studies on the diagnosis of diabetic foot infection. On the basis of predetermined criteria, we reviewed prospective controlled, as well as noncontrolled, studies in any language, seeking translations for those not in English. We then developed evidence statements on the basis of the included papers. RESULTS: From the 4242 records screened, we selected 35 papers that met our inclusion criteria. The quality of all but one of the evidence statements was low because of the weak methodology of nearly all of the studies. The available data suggest that diagnosing diabetic foot infections on the basis of clinical signs and symptoms and classified according to the International Working Group of the Diabetic Foot scheme correlates with the patient's likelihood of ulcer healing, of lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers are supportive, but not diagnostic, of soft tissue or bone infection. In patients with suspected diabetic foot osteomyelitis, both a positive probe-to-bone test and an elevated erythrocyte sedimentation rate are strongly associated with its presence. Culturing tissue samples of soft tissues or bone, when care is taken to avoid contamination, provides more accurate microbiological information than culturing superficial (swab) samples. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis, but advanced imaging methods help in cases when either the diagnosis or the localization of infection is uncertain. CONCLUSION: The results of this first reported systematic review on the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is a need for more prospective controlled studies of high quality.

Guidelines on the diagnosis and treatment of foot infection in persons with diabetes (IWGDF 2019 update).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the prevention and management of diabetic foot disease since 1999. This guideline is on the diagnosis and treatment of foot infection in persons with diabetes and updates the 2015 IWGDF infection guideline. On the basis of patient, intervention, comparison, outcomes (PICOs) developed by the infection committee, in conjunction with internal and external reviewers and consultants, and on systematic reviews the committee conducted on the diagnosis of infection (new) and treatment of infection (updated from 2015), we offer 27 recommendations. These cover various aspects of diagnosing soft tissue and bone infection, including the classification scheme for diagnosing infection and its severity. Of note, we have updated this scheme for the first time since we developed it 15 years ago. We also review the microbiology of diabetic foot infections, including how to collect samples and to process them to identify causative pathogens. Finally, we discuss the approach to treating diabetic foot infections, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and for bone infections, when and how to approach surgical treatment, and which adjunctive treatments we think are or are not useful for the infectious aspects of diabetic foot problems. For this version of the guideline, we also updated four tables and one figure from the 2016 guideline. We think that following the principles of diagnosing and treating diabetic foot infections outlined in this guideline can help clinicians to provide better care for these patients.

Definitions and criteria for diabetic foot disease.

Multiple disciplines are involved in the management of diabetic foot disease, and a common vocabulary is essential for clear communication. Based on the systematic reviews of the literature that form the basis of the International Working Group on the Diabetic Foot (IWGDF) Guidelines, the IWGDF has developed a set of definitions and criteria for diabetic foot disease. This document describes these definitions and criteria. We suggest these definitions be used consistently in both clinical practice and research to facilitate clear communication between professionals.

Principles and practice of antibiotic stewardship in the management of diabetic foot infections.

PURPOSE OF REVIEW: Systemic antibiotic therapy in persons with a diabetic foot infection (DFI) is frequent, increasing the risk of promoting resistance to common pathogens. Applying principles of antibiotic stewardship may help avoid this problem. RECENT FINDINGS: We performed a systematic review of the literature, especially seeking recently published studies, for data on the role and value of antibiotic stewardship (especially reducing the spectrum and duration of antibiotic therapy) in community and hospital populations of persons with a DFI. SUMMARY: We found very few publications specifically concerning antibiotic stewardship in persons with a DFI. The case-mix of these patients is substantial and infection plays only one part among several chronic problems. As with other types of infections, attempting to prevent infections and avoiding or reducing the spectrum and duration of antibiotic therapy are perhaps the best ways to reduce antibiotic prescribing in the DFI population. The field is complex and necessitates knowledge over the current scientific literature and clinical experience. On a larger scale, clinical pathways, guidelines, and recommendations are additionally supportive.

Four versus six weeks of antibiotic therapy for osteoarticular infections after implant removal: a randomized trial.

BACKGROUND: The optimal duration of antibiotic therapy for treating orthopaedic implant infections after surgical drainage and complete implant removal is unknown. METHODS: This was a single-centre, unblinded, prospective trial randomizing (1:1) eligible patients to either 4 or 6 weeks of systemic, pathogen-targeted antibiotic therapy. Clinical trial registration number: ClinicalTrials.gov (NCT0362209). RESULTS: We analysed 123 eligible patients (62 in the 4 week antibiotic arm and 61 in the 6 week arm) in the ITT analysis. The patients' median age was 64 years, 75 (61%) were men and 38 (31%) were immunocompromised. The most common types of infection treated included: two-stage exchange procedure for prosthetic joint infection (n = 38); orthopaedic plate infection (44) and infected nail implants (11). The median duration of post-explant intravenous antibiotic therapy was 4 days. Overall, 120 episodes (98%) were cured microbiologically and 116 (94%) clinically after a median follow-up period of 2.2 years. During follow-up, four patients had a clinical recurrence with a pathogen other than the initial causative agent. We noted recurrence of clinical infection in four patients in the 4 week arm and three patients in the 6 week arm (4/62 versus 3/61; χ2 test; P = 0.74); in all cases, this occurred at around 2 months following the end of antibiotic treatment. CONCLUSIONS: We found no statistically significant difference in the rates of clinical or microbiological remission between patients randomized to only 4 compared with 6 weeks of systemic antibiotic therapy after removal of an infected osteoarticular implant.

Remission in diabetic foot infections: Duration of antibiotic therapy and other possible associated factors.

AIM: To determine the most appropriate duration of antibiotic therapy for diabetic foot infections (DFIs). METHODS: Using a clinical pathway for adult patients with DFIs (retrospective cohort analysis), we created a cluster-controlled Cox regression model to assess factors related to remission of infection, emphasizing antibiotic-related variables. We excluded total amputations as a result of DFI and DFI episodes with a follow-up time of <2 months. RESULTS: Among 1018 DFI episodes in 482 patients, we identified 392 episodes of osteomyelitis, 626 soft tissue infections, 246 large abscesses, 322 episodes of cellulitis and 335 episodes of necrosis; 313 cases involved revascularization. Patients underwent surgical debridement for 824 episodes (81%), of which 596 (59%) required amputation. The median total duration of antibiotic therapy was 20 days. After a median follow-up of 3 years, 251 of the episodes (24.7%) were followed by ≥1 additional episode(s). Comparing patients with and without additional episodes, risk of recurrence was lower in those who underwent amputation, had type 1 diabetes, or underwent revascularization. On multivariate analysis including the entire study population, risk of remission was inversely associated with type 1 diabetes (hazard ratio [HR] 0.3, 95% confidence interval [CI] 0.2-0.6). Neither duration of antibiotic therapy nor parenteral treatment affected risk of recurrence (HR 1.0, 95% CI 0.99-1.01 for both). Similarly, neither >3 weeks versus <3 weeks of therapy, nor >1 week versus <1 week of intravenous treatment affected recurrence. In stratified analyses for both soft tissue DFIs or osteomyelitis separately, we did not observe associations of antibiotic duration with microbiological or clinical recurrences of DFI. The HRs were 1.0 (95% CI 0.6-1.8) for an antibiotic duration >3 weeks overall and 0.6 (95% CI 0.2-1.3) for osteomyelitis cases only. Plotting of duration of antibiotic therapy failed to identify any optimal threshold for preventing recurrences. CONCLUSIONS: Our analysis found no threshold for the optimal duration or route of administration of antibiotic therapy to prevent recurrences of DFI. These limited data might support possibly shorter treatment duration for patients with DFI.