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.

Evaluation of the Genmark ePlex® and QIAstat-Dx® respiratory pathogen panels in detecting bacterial targets in lower respiratory tract specimens.

BACKGROUND: The ePlex® and QIAstat-Dx® respiratory pathogen panels detect multiple respiratory pathogens, mainly viruses but also Legionella pneumophila, Mycoplasma pneumoniae and Bordetella pertussis. The assays have been marketed for use in nasopharyngeal swab specimens. For diagnosing bacterial pneumonia, lower respiratory tract (LRT) specimens are indicated. Aim of this study was to evaluate the performance of these syndromic panels for these three bacterial targets in samples from the LRT. Fifty-six specimens were collected from our repositories, five negative samples and fifty-one samples which had been previously tested positive with the routine diagnostic real-time PCR assays for Legionella spp. (N = 20), Bordetella spp. (N = 16) or M. pneumoniae (N = 15). RESULTS: The QIAstat-Dx Respiratory Panel V2 (RP) assay detected all of the L. pneumophila and B. pertussis positive samples but only 11/15 (73.3 %) of the M. pneumoniae targets. The ePlex Respiratory Pathogen Panel (RPP) assay detected 10/14 (71.4 %) of the L. pneumophila targets, 8/12 (66.7 %) of the B. pertussis positive samples and 13/15 (86.7 %) of the M. pneumoniae targets. CONCLUSIONS: No false-positive results were reported for all three bacterial pathogens by both assays. The clinical performance of both assays depended highly on the bacterial load in the sample and the type of specimen under investigation.

Clinical implications of bile cultures obtained during pancreatoduodenectomy: a cohort study and meta-analysis.

BACKGROUND: The association between intraoperative bile cultures and infectious complications after pancreatoduodenectomy remains unclear. This cohort study and meta-analysis aimed to determine the predictive role of intraoperative bile cultures in abdominal infectious complications after pancreatoduodenectomy. METHODS: The cohort study included 114 patients undergoing pancreatoduodenectomy. Regression analyses were used to estimate the odds to develop an organ space infection (OSI) or isolated OSI (OSIs without a simultaneous complication potentially contaminating the intraabdominal space) after a positive bile culture. A systematic review and meta-analysis was performed on abdominal infectious complications (Mantel-Haenszel fixed-effect model). RESULTS: The positive bile culture rate was 61%, predominantly in patients after preoperative biliary drainage (98% vs 26%, p < 0.001). OSIs occurred in 35 patients (31%) and isolated OSIs in nine patients (8%) and were not associated with positive bile cultures (OSIs: odds ratio = 0.6, 95% CI = 0.25-1.23, isolated OSIs: odds ratio = 0.77, 95% CI = 0.20-3.04). In the meta-analysis, 15 studies reporting on 2047 patients showed no association between positive bile cultures and abdominal infectious complications (pooled odds ratio = 1.3, 95% CI = 0.98-1.65). CONCLUSION: Given the rare occurrence of isolated OSIs and similar odds for patients with positive and negative bile cultures to develop abdominal infectious complications, routine performance of bile cultures should be reconsidered.

[Emergence of amatoxin poisoning in the Netherlands]. / De giftige groene knolamaniet.

CASE DESCRIPTION: A 34-year-old woman from Thai origin developed acute liver failure after ingestion of a soup which contained the death cap (Amanita phalloides). BACKGROUND: In patients with poisoning due to amatoxin-containing mushrooms, gastro-intestinal complaints usually develop several hours after ingestion, followed by acute hepatic failure which occasionally leads to death. The incidence of reported mushroom poisonings in the Netherlands has increased in 2019, which is possibly associated with migration of asylum seekers who regularly pick and eat mushrooms. CONCLUSION: In the Netherlands mushroom intoxication is rare. Therefore, there is a lack of knowledge among health care personnel and foragers. The present case report highlights the importance of awareness of the poisonous death cap to prevent intoxications and optimize treatment decisions.

The infected diabetic foot: Can serum biomarkers predict osteomyelitis after hospital discharge for diabetic foot infections?

The aim of this study is to evaluate serum biomarkers to monitor high-risk patients for reinfection of bone. Thirty-five patients were prospectively enrolled with moderate to severe diabetic foot infections with suspicion of osteomyelitis. Bone samples were obtained for culture and histology. Clinical characteristics and outcomes of patients were compared using χ2 square test. Biomarkers (white blood cell count, erythrocyte sedimentation rate, c-reactive protein, procalcitonin, interleukin-6, interleukin-8, and monocyte chemoattractant protein 1) were assessed at baseline, 3, and 6 weeks after treatment initiation and evaluated for correlation with reinfection of bone. After 6 weeks of antibiotic treatment, ESR at 73.5 mm/h (sensitivity 62.5%, specificity 100%, area under the receiver operating characteristic (AUROC) 0.7839, 95% CI 0.54-1.00, P < .01) and IL-8 at 15.09 mg/dL (sensitivity 42.9%, specificity 92.0% AUROC 0.6286, 95% CI 0.36-0.90, P = .0496) were associated with reinfection of bone. An increase in IL-8 from week 0 to 6 >0.95 mg/dL was associated with reinfection (sensitivity 71%, specificity 72% AUROC 0.7057, 95% CI 0.49-0.92, P = .04). An ESR change from week 0-6 of -16.5% (sensitivity 71.4%, specificity 86.4% AUROC 0.7403, 95% CI 0.48-1.00, P = .02), CRP (-)74.4% (sensitivity 66.7%, specificity 91.3% AUROC 0.7174, 95% CI 0.40-1.00, P = .04), IL-6 (-)49.9% (sensitivity 71.4%, specificity 76% AUROC 0.7371, 95% CI 0.47-1.00, P = .04), and IL-8 29% (sensitivity 85.7%, specificity 56.0% AUROC of 0.7343, 95% CI 0.54-0.93, P = .048) were associated with increased risk of reinfection. Pilot data suggest that serum biomarkers (ESR, IL8 and IL6, MCP-1) may be correlated with developing osteomyelitis and could be used to monitor high-risk patients for reinfection.

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.

Pragmatic randomised controlled trial of a personalised intervention for carers of people requiring home oxygen therapy.

We used a pragmatic randomised controlled trial to evaluate a behavioural change strategy targeting carers of chronically hypoxaemic patients using long-term home oxygen therapy. Intervention group carers participated in personalised educational sessions focusing on motivating carers to take actions to assist patients. All patients received usual care. Effectiveness was measured through a composite event of patient survival to hospitalisation, residential care admission or death to 12 months. Secondary outcomes at baseline, 3, 6 and 12 months included carer and patient emotional and physical well-being. No difference between intervention (n = 100) and control (n = 97) patients was found for the composite outcome (hazard ratio (HR) 1.22, 95% confidence interval (CI) = 0.89, 1.68; p = 0.22). Improved fatigue, mastery, vitality and general health occurred in intervention group patients (all p values < 0.05). No benefits were seen in carer outcomes. Mortality was significantly higher in intervention patients (HR = 2.01, 95% CI = 1.00, 4.14; p = 0.05; adjusted for Australia-modified Karnofsky Performance Status), with a significant diagnosis-intervention interaction (p = 0.028) showing higher mortality in patients with COPD (HR 4.26; 95% CI = 1.60, 11.35) but not those with interstitial lung disease (HR 0.83; 95% CI = 0.28, 2.46). No difference was detected in the primary outcome, but patient mortality was higher when carers had received the intervention, especially in the most disabled patients. Trials examining behavioural change interventions in severe disease should stratify for functionality, and both risks and benefits should be independently monitored. Trial registration: Australian New Zealand Clinical Trials Registry (ACTRN12607000177459).

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.

Complications during the treatment of diabetic foot osteomyelitis.

AIM: To identify complications of medical treatment in patients with diabetic foot osteomyelitis (DFO). METHODS: We reviewed 143 records of consecutive patients admitted with DFO, confirmed by bone histopathology or culture. Complications monitored included acute kidney injuries (AKI), development of methicillin-resistant Staphylococcus aureus (MRSA) and vancomycin-resistant Enterococcus (VRE), gastrointestinal complications, and venous catheter related complications during a 12months follow-up period. RESULTS: Forty-seven AKI episodes were reported during follow-up; half occurred during the first hospitalization with involvement of antimicrobial therapy in 14 events (29.8%). Patients with AKI were more likely to have recurrent ulcerations (69.2% vs. 45.2%, p=0.02), recurrent infections (38.5% vs. 17.3%, p=0.01), and recurrent hospitalizations (43.6% vs. 28.8%, p=0.02) during follow-up. Only 14 MRSA isolates were found in bone samples at baseline (9.8%). Resistant strains of MRSA and VRE were identified in twenty-one patients (14.7%) during follow-up. Patients re-hospitalized for infection were more likely to have resistant bacterial strains (52.6% vs. 25.8%, p=0.02). CONCLUSIONS: In this study, the rates of VRE and MRSA in bone biopsies of patients with DFO were lower than in previous reports. Acute kidney injury occurred frequently in our patient population but might not be associated with antibiotic exposure.

Split-Thickness Skin Grafts to the Foot and Ankle of Diabetic Patients.

BACKGROUND: There is an increased prevalence of foot ulceration in patients with diabetes, leading to hospitalization. Early wound closure is necessary to prevent further infections and, ultimately, lower-limb amputations. There is no current evidence stating that an elevated preoperative hemoglobin A1c (HbA1c) level is a contraindication to skin grafting. The purpose of this review was to determine whether elevated HbA1c levels are a contraindication to the application of skin grafts in diabetic patients. METHODS: A retrospective review was performed of 53 consecutive patients who underwent split-thickness skin graft application to the lower extremity between January 1, 2012, and December 31, 2015. A uniform surgical technique was used across all of the patients. A comparison of HbA1c levels between failed and healed skin grafts was reviewed. RESULTS: Of 43 surgical sites (41 patients) that met the inclusion criteria, 27 healed with greater than 90% graft take and 16 had a skin graft that failed. There was no statistically significant difference in HbA1c levels in the group that healed a skin graft compared with the group in which skin graft failed to adhere. CONCLUSIONS: Preliminary data suggest that an elevated HbA1c level is not a contraindication to application of a skin graft. The benefits of early wound closure outweigh the risks of skin graft application in patients with diabetes.

Erythrocyte sedimentation rate and C-reactive protein to monitor treatment outcomes in diabetic foot osteomyelitis.

This study sought to evaluate the effectiveness of the inflammatory markers, erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP), in monitoring treatment of osteomyelitis in the diabetic foot. We screened 150 charts of patients admitted to our hospital with diabetic foot osteomyelitis (DFO), confirmed by positive results of bone culture and/or histopathology. We included patients who had an initial ESR/CRP within 72 hours of admission and two reported follow-up values. We dichotomised patients based on the outcomes wound healing, re-infection, recurrent ulceration, re-hospitalisation, additional surgery, re-amputation and death, all within 12 months, and analysed the trajectories of the markers over time. Our primary outcome, DFO remission, was defined as wound healing within 12 months of follow-up without re-infection. We included 122 subjects; 65 patients (53·3%) had a combination of positive culture and histopathology. Factors associated with DFO remission (n = 46) were a lower white blood count (WBC) at admission (P = 0·006) and a higher glomerular filtration rate (GFR, P = 0·049). Factors associated with healing were a lower WBC (P = 0·004), a higher GFR (P = 0·01), longer wound duration before admission (P = 0·01), location of the ulcer on the great toe (P = 0·01) and higher glycated haemoglobin (P = 0·03). Logistic regression analysis demonstrated no associations between DFO remission and other variables collected. Trajectories of the inflammatory markers showed an association between stagnating values of ESR and CRP and poor clinical outcomes. In this study population, the trajectories of both ESR and CRP during 12 months follow-up suggest a predictive role of both inflammatory markers when monitoring treatment of DFO.

The value of inflammatory markers to diagnose and monitor diabetic foot osteomyelitis.

In this study, we assessed the effectiveness of inflammatory markers to diagnose and monitor the treatment of osteomyelitis in the diabetic foot. We evaluated 35 consecutive patients admitted to our hospital with infected foot ulcers. Patients were divided in two groups based on the results of bone culture and histopathology: osteomyelitis and no osteomyelitis. The erythrocyte sedimentation rate (ESR), C-reactive protein (CRP), procalcitonin (PCT), interleukin-6 (IL-6), interleukin-8 (IL-8), tumor necrosis factor alpha (TNFα), monocyte chemotactic protein-1 (MCP-1) and macrophage inflammatory protein-1 alpha (MIP1α) were measured at baseline after 3 and 6 weeks of standard therapy. PCT levels in the osteomyelitis group were significantly higher at baseline than in the group with no osteomyelitis (P = 0·049). There were no significant differences between the two groups in the levels of the other markers. CRP, ESR, PCT and IL-6 levels significantly declined in the group with osteomyelitis after starting therapy, while MCP-1 increased (P = 0·002). TNFα and MIP1α levels were below range in 80 out of 97 samples and therefore not reported. Our results suggest that PCT might be useful to distinguish osteomyelitis in infected foot ulcers. CRP, ESR, PCT and IL-6 are valuable when monitoring the effect of therapy.

Comparison Between Tc-99m WBC SPECT/CT and MRI for the Diagnosis of Biopsy-proven Diabetic Foot Osteomyelitis.

OBJECTIVE: Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO), with a reported accuracy of 79%. The gold standard to diagnose osteomyelitis is bone biopsy, with a positive culture and/or histopathology findings consistent with osteomyelitis. The purposes of this study are to assess the accuracy of technetium-99m (Tc-99m) labeled white blood cell (WBC) single-photon emission computed tomography/computed tomography (SPECT/CT) hybrid imaging for diagnosing DFO confirmed by bone biopsy and to compare that to the diagnostic accuracy of an MRI. MATERIALS AND METHODS: The authors performed a retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large municipal hospital between 2010 and 2013. Patients were selected on the basis of whether they received an MRI or a SPECT/CT. Patients whose scans were not within a clinically relevant time frame of the biopsy were excluded. Imaging results were correlated with probability of osteomyelitis determined by bone biopsy. RESULTS: For inclusion criteria, 110 patients met the study's criteria: 52 SPECT/CT patients and 58 MRI patients. The sensitivity, specificity, positive predictive value, and negative predictive value of SPECT/CT were 89%, 35%, 74%, and 60%, respectively; the corresponding values for MRI were 87%, 37%, 74%, and 58%, respectively. There were no significant differences in accuracy of diagnosing DFO between imaging techniques. CONCLUSION: This data suggests that the diagnostic accuracy of SPECT/CT imaging in DFOs is similar to an MRI.

Update on the Role of Infection and Biofilms in Wound Healing: Pathophysiology and Treatment.

BACKGROUND: Chronic wounds, and among these infected diabetic foot ulcers, are a worldwide problem. The poor treatment outcomes result in high healthcare costs, amputations, a decreased quality of life, and an increased mortality. These outcomes are influenced by several factors, including biofilm formation. A biofilm consists of pathogenic bacteria that are encased in an exopolysaccharide layer and communicate through secretion of signaling molecules. Bacteria that live in a biofilm are refractory to host responses and treatment. METHODS: We performed a nonsystematic review of the currently published to-date medical biofilm literature. The review summarizes the evidence of biofilm in chronic wounds, the role of biofilm in wound healing, detection of biofilm, and available antibiofilm treatments. Articles containing basic science and clinical research, as well as systematic reviews, are described and evaluated. The articles have variable levels of evidence. All articles have been peer reviewed and meet the standards of evidence-based medicine. RESULTS: Both animal and human studies have identified biofilm in chronic wounds and have suggested that healing might be influenced by its presence. A promising development in biofilm detection is rapid molecular diagnostics combined with direct microscopy. This technique, rather than classic culture, might support individualized treatment in the near future. A wide range of treatments for chronic wounds also influence biofilm formation. Several agents that specifically target biofilm are currently being researched. CONCLUSIONS: Biofilm formation has a substantial role in chronic wounds. Several diagnostic and therapeutic methods against biofilm are currently being developed.