Diagnosis of infection in the foot of patients with 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 potential mortality and present formidable challenges in surgical and antimicrobial treatment. METHODS: In June 2022, we searched the literature using PubMed and EMBASE for published studies on the diagnosis of diabetic foot infection (DFI). On the basis of pre-determined criteria, we reviewed prospective controlled, as well as non-controlled, studies in English. We then developed evidence statements based on the included papers. RESULTS: We selected a total of 64 papers that met our inclusion criteria. The certainty of the majority 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/Infectious Diseases Society of America scheme correlates with the patient's likelihood of the need for hospitalisation, lower extremity amputation, and risk of death. Elevated levels of selected serum inflammatory markers such as erythrocyte sedimentation rate (ESR), C-reactive protein and procalcitonin are supportive, but not diagnostic, of soft tissue infection. 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. Although non-culture techniques, especially next-generation sequencing, are likely to identify more bacteria from tissue samples including bone than standard cultures, no studies have established a significant impact on the management of patients with DFIs. In patients with suspected diabetic foot osteomyelitis, the combination of a positive probe-to-bone test and elevated ESR supports this diagnosis. Plain X-ray remains the first-line imaging examination when there is suspicion of diabetic foot osteomyelitis (DFO), but advanced imaging methods including magnetic resonance imaging (MRI) and nuclear imaging when MRI is not feasible help in cases when either the diagnosis or the localisation of infection is uncertain. Intra-operative or non-per-wound percutaneous biopsy is the best method to accurately identify bone pathogens in case of a suspicion of a DFO. Bedside percutaneous biopsies are effective and safe and are an option to obtain bone culture data when conventional (i.e. surgical or radiological) procedures are not feasible. CONCLUSIONS: The results of this systematic review of the diagnosis of diabetic foot infections provide some guidance for clinicians, but there is still a need for more prospective controlled studies of high quality.

IWGDF/IDSA guidelines on the diagnosis and treatment of diabetes-related foot infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

Interventions in the management of diabetes-related foot infections: 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 from 30 June 2018 to 30 June 2022. We combined this search with our previous literature search of a systematic review performed in 2020, in which the infection committee of the International Working Group on the Diabetic Foot searched the literature until June 2018. We defined the context of the literature by formulating clinical questions of interest, then developing structured clinical questions (Patients-Intervention-Control-Outcomes) 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 methodological quality. Our literature search identified a total of 5,418 articles, of which we selected 32 for full-text review. Overall, the newly available studies we identified since 2018 do not significantly modify the body of the 2020 statements for the interventions in the management of diabetes-related foot infections. The recent data confirm that outcomes in patients treated with the different antibiotic regimens for both skin and soft tissue infection and osteomyelitis of the diabetes-related foot are broadly equivalent across studies, with a few exceptions (tigecycline not non-inferior to ertapenem [±vancomycin]). The newly available data suggest that antibiotic therapy following surgical debridement for moderate or severe infections could be reduced to 10 days and to 3 weeks for osteomyelitis following surgical debridement of bone. Similar outcomes were 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 recent adjunctive therapies, such as cold plasma for infected foot ulcers and bioactive glass for osteomyelitis. Our updated systematic review confirms a trend to a better quality of the most recent trials and the need for further well-designed trials to produce higher quality evidence to underpin our recommendations.

IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023).

The International Working Group on the Diabetic Foot (IWGDF) has published evidence-based guidelines on the management and prevention of diabetes-related foot diseases since 1999. The present guideline is an update of the 2019 IWGDF guideline on the diagnosis and management of foot infections in persons with diabetes mellitus. The Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework was used for the development of this guideline. This was structured around identifying clinically relevant questions in the P(A)ICO format, determining patient-important outcomes, systematically reviewing the evidence, assessing the certainty of the evidence, and finally moving from evidence to the recommendation. This guideline was developed for healthcare professionals involved in diabetes-related foot care to inform clinical care around patient-important outcomes. Two systematic reviews from 2019 were updated to inform this guideline, and a total of 149 studies (62 new) meeting inclusion criteria were identified from the updated search and incorporated in this guideline. Updated recommendations are derived from these systematic reviews, and best practice statements made where evidence was not available. Evidence was weighed in light of benefits and harms to arrive at a recommendation. The certainty of the evidence for some recommendations was modified in this update with a more refined application of the GRADE framework centred around patient important outcomes. This is highlighted in the rationale section of this update. A note is also made where the newly identified evidence did not alter the strength or certainty of evidence for previous recommendations. The recommendations presented here continue to cover various aspects of diagnosing soft tissue and bone infections, including the classification scheme for diagnosing infection and its severity. Guidance on how to collect microbiological samples, and how to process them to identify causative pathogens, is also outlined. Finally, we present the approach to treating foot infections in persons with diabetes, including selecting appropriate empiric and definitive antimicrobial therapy for soft tissue and bone infections; when and how to approach surgical treatment; and which adjunctive treatments may or may not affect the infectious outcomes of diabetes-related foot problems. We believe that following these recommendations will help healthcare professionals provide better care for persons with diabetes and foot infections, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

Individualised screening of diabetic foot: creation of a prediction model based on penalised regression and assessment of theoretical efficacy.

AIMS/HYPOTHESIS: A large proportion of people with diabetes do not receive proper foot screening due to insufficiencies in healthcare systems. Introducing an effective risk prediction model into the screening protocol would potentially reduce the required screening frequency for those considered at low risk for diabetic foot complications. The main aim of the study was to investigate the value of individualised risk assignment for foot complications for optimisation of screening. METHODS: From 2015 to 2020, 11,878 routine follow-up foot investigations were performed in the tertiary diabetes clinic. From these, 4282 screening investigations with complete data containing all of 18 designated variables collected at regular clinical and foot screening visits were selected for the study sample. Penalised logistic regression models for the prediction of loss of protective sensation (LOPS) and loss of peripheral pulses (LPP) were developed and evaluated. RESULTS: Using leave-one-out cross validation (LOOCV), the penalised regression model showed an AUC of 0.84 (95% CI 0.82, 0.85) for prediction of LOPS and 0.80 (95% CI 0.78, 0.83) for prediction of LPP. Calibration analysis (based on LOOCV) presented consistent recall of probabilities, with a Brier score of 0.08 (intercept 0.01 [95% CI -0.09, 0.12], slope 1.00 [95% CI 0.92, 1.09]) for LOPS and a Brier score of 0.05 (intercept 0.01 [95% CI -0.12, 0.14], slope 1.09 [95% CI 0.95, 1.22]) for LPP. In a hypothetical follow-up period of 2 years, the regular screening interval was increased from 1 year to 2 years for individuals at low risk. In individuals with an International Working Group on the Diabetic Foot (IWGDF) risk 0, we could show a 40.5% reduction in the absolute number of screening examinations (3614 instead of 6074 screenings) when a 10% risk cut-off was used and a 26.5% reduction (4463 instead of 6074 screenings) when the risk cut-off was set to 5%. CONCLUSIONS/INTERPRETATION: Enhancement of the protocol for diabetic foot screening by inclusion of a prediction model allows differentiation of individuals with diabetes based on the likelihood of complications. This could potentially reduce the number of screenings needed in those considered at low risk of diabetic foot complications. The proposed model requires further refinement and external validation, but it shows the potential for improving compliance with screening guidelines.

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.

A randomized, placebo-controlled study of chitosan gel for the treatment of chronic diabetic foot ulcers (the CHITOWOUND study).

INTRODUCTION: To assess the efficacy of a chitosan-based gel (ChitoCare) for the treatment of non-healing diabetic foot ulcers (DFUs). RESEARCH DESIGN AND METHODS: Forty-two patients with chronic DFUs were randomized to the ChitoCare or placebo gel for a 10-week treatment period and 4-week follow-up. The primary study end point was the rate of complete wound closure at week 10, presented as relative rate. RESULTS: Thirty patients completed the 10-week treatment and 28 completed the 4-week follow-up. The ChitoCare arm achieved 16.7% complete wound closure at week 10 vs 4.2% in the placebo arm (p=0.297), 92.0% vs 37.0% median relative reduction in wound surface area from baseline at week 10 (p=0.008), and 4.62-fold higher likelihood of achieving 75% wound closure at week 10 (p=0.012). Based on the results of the Bates-Jensen Wound Assessment Tool, the wound state at week 10 and the relative improvement from the baseline were significantly better (median 20 vs 24 points, p=0.018, and median 29.8% vs 3.6%, p=0.010, respectively). CONCLUSIONS: ChitoCare gel increased the rate of the DFU healing process. Several secondary end points significantly favored ChitoCare gel. TRIAL REGISTRATION NUMBER: NCT04178525.

Possible Advantages of S53P4 Bioactive Glass in the Treatment of Septic Osteoarthritis of the First Metatarsophalangeal Joint in the Diabetic Foot.

Biomechanically, the great toe with its metatarsophalangeal (MTP) joint plays a key role in standing and walking, making the first MTP joint one of the main predilection sites for ulcer formation, and consequently for bone and joint infection and even amputation. If conservative treatment fails, the main goal of surgery is to remove all infected tissue and preserve the first ray. To improve surgical outcomes, development of new biomaterials like Bioactive Glass S53P4 has begun. Bioactive Glass is useful because of its antibacterial properties; furthermore, its osteostimulative and osteoconductive qualities make the bone substitute particularly suitable as a bone defect filler for the treatment of osteomyelitis. The aim of our retrospective observational study was to compare the outcomes following ulcerectomy with segmental resection of the infected joint and bone and temporary stabilization with an external fixator, both with and without added Bioactive Glass. A comparison of added Bioactive Glass with the traditional surgical treatment in septic osteoarthritis of the first MTP joint showed Bioactive Glass to be effective. During a one-year follow-up, patients with Bioactive Glass required no additional antibiotic therapy or surgical intervention. Bioactive Glass, when applied to the diabetic foot, showed itself to be a safe bone substitute biomaterial.

Skin blood flow and its oscillatory components in patients with acute myocardial infarction.

BACKGROUND/AIMS: Laser Doppler flowmetry (LDF) was used to determine the influence of acute myocardial infarction (AMI) and of successful reperfusion treatment on basal skin blood flow and its oscillatory components. METHODS: Skin LDF was performed on all extremities in 58 patients 4-9 days after AMI (Killip class I), and in 71 healthy age- and sex-matched controls. Wavelet analysis was applied to evaluate oscillatory components within the interval 0.005-2 Hz. RESULTS: AMI patients had reduced mean flow (p < 0.01) and oscillatory components (p < 0.04) in all extremities. Reperfused (n = 40), compared to nonreperfused (n = 18), patients had higher mean flow and total spectral amplitude at all recording points. The difference was statistically significant only in legs (group median LDF in the left leg was 9.68 AU for reperfused and 5.71 AU for nonreperfused patients, p < 0.04, and 11.47 and 4.24 AU in the right leg, p < 0.01). Reperfused patients had significantly higher total spectral amplitude in both legs (p < 0.04). CONCLUSIONS: In AMI patients, reduced skin blood flow and its oscillatory components may reflect ongoing neurohumoral activation despite absence of clinically apparent heart failure. The reduction of blood flow and its oscillatory components was larger in nonreperfused AMI patients, although they had a comparable left ventricular function.

An exploration of diabetic foot screening procedures data by a multiple correspondence analysis.

AIMS: Gangrene and amputation are among most feared complications of diabetes mellitus. Early detection of patients at high risk for foot ulceration can prevent foot complications. Regular foot screening (medical history, foot examination and classification into risk groups) was introduced at the out-patient diabetes clinic in Ljubljana in November 1996. We aimed to explore the relationships between the observed variables, check the appropriateness of the risk status classification and of the post-screening decisions. METHODS: The data of 11.594 patients, obtained in 18 years, were analysed by multiple correspondence analysis (MCA). Most of the observed variables were categorical. RESULTS: The majority of the screened population was free of foot complications. We demonstrated an increasing frequency and severity of foot problems with an increasing age, as well as the association between the loss of protective sensation and the history of foot ulceration, foot deformity and callus formation, the history of foot ulcer or amputation and acute foot ulceration. A new finding was that the location of foot deformity points was closer to female than male gender, indicating the possible role of fashionable high-heel footwear. The appropriateness of therapeutic decisions was confirmed: the points representing absent foot pulses and referral to vascular specialist were close together, as well as points representing foot deformity and special footwear prescription or callus formation and referral to pedicurist. CONCLUSIONS: MCA was applied to the data on foot pathology in the population attending the out-patient diabetes clinic. The method proved to be a useful statistical tool for analysing the data of screening procedures.

Macro- and microcirculation in the lower extremities--possible relationship.

AIMS: Impaired blood supply is a significant risk factor for diabetic foot ulceration and gangrene. A possible relationship between peripheral macroangiopathy and the spectral components of microvascular skin blood flow in the lower extremities was tested in diabetic patients (DP) and non-diabetic subjects (C). PATIENTS AND METHODS: Basal skin blood flow (BSBF) was recorded for 30min at the right and left medial malleolus (predominantly nutritive capillary circulation) by laser Doppler flowmetry in 64 DP and 31 C. Its oscillatory components were analyzed using wavelet transform. Peripheral arterial obliterative disease (PAOD) was defined according to ankle/brachial index (ABI): PAOD+ (ABI<0.9: 21 DP, 12 C), PAOD- (ABI 0.91-1.3: 43 DP, 19 C). RESULTS: No statistically significant differences in BSBF and its oscillatory components were observed between PAOD+ and PAOD-, neither in DP nor in C. In DP, the spectral component of microvascular flow associated with endothelial activity was in significant positive correlation with systolic pressures on brachial and dorsal pedal artery (p=0.001 and 0.010, respectively). CONCLUSIONS: These results indicate that mean BSBF and its oscillatory components do not change with diabetic PAOD; however there is a strong correlation between systolic pressure and the oscillatory components of BSBF related to endothelial activity manifested in the frequency interval 0.0095-0.02Hz.