Diabetic Foot Osteomyelitis Research Articles

Local Antibiotic Delivery Systems in the Surgical Treatment of Diabetic Foot Osteomyelitis: Again, No Benefit?

This retrospective study aimed to compare the outcomes and healing parameters of 3 groups of surgical treatment combined with and without local antibiotic administration in diabetic foot osteomyelitis (DFO). Overall, 25 patients with DFO who met the criteria were included in the study. Surgical debridement was used with systemic antibiotic administration alone (group A; n = 8) or combined with local application of antibiotic-loaded polymethylmethacrylate beads (group B; n = 9) or antibiotic-loaded hydroxyapatite and calcium sulfate beads (group C; n = 8). In total, 87.5% patients in group A, 100% in group B, and 87.5% in group C healed (P = .543). Median time to healing was 17 weeks in group A, 18 weeks in group B, and 19 weeks in group C (P = .094). One patient (12.5%) in group A was amputated. DFO recurrence rate was 12.5% in group A and 12.5% in group C (P = .543). Median hospitalization was 9 days in group A, 8 days in group B, and 9 days in group C (P = .081). In conclusion, adjunctive local antibiotic therapy was not shown to improve outcomes in surgically treated DFO.

A Shorter Antibiotic Course for Diabetic Foot Osteomyelitis

Current guidelines recommend 4 to 6 weeks of antibiotic therapy for diabetic foot osteomyelitis (DFO). However, longer courses (>6 weeks) are

Diabetic foot infection and osteomyelitis. Are deep-tissue cultures necessary?

Diabetic foot infections (DFIs) are common and difficult to treat. The objective of this study was to compare swab and tissue cultures as indicators of appropriate treatment of DFIs. This is a prospective study conducted during a 4-year period. All patients with DFIs and/or diabetic foot osteomyelitis (DFO) admitted to the University Hospital of Heraklion, Greece, were included. Clinical data were collected, while cultures taken with swabs and/or tissue biopsies were used as indicators of the microbiological cause and the appropriate treatment. In total, 83 individuals (62.7% males) with mean age of 72 years, were enrolled. Coexisting osteomyelitis was present in 18.1%. From tissue and pus cultures, 131 and 176 pathogens, respectively, were isolated. Gram-positive aerobes were the most common microorganisms, followed by Gram-negatives. Infection was polymicrobial in 40 (70.2%) out of 57 patients with tissue culture and in 54 (75.0%) out of 72 with pus culture. Microbiological results from tissue cultures were compatible with those from pus at a rate of 80%, while in cases of osteomyelitis concordance reached 100%. Multidrug-resistant organisms (MDROs) were isolated from 32 (24.4%) tissue and 44 (25%) pus cultures (p=0.910). Initial empirical antimicrobial treatment was considered inappropriate in 44.6% of cases. A high concordance between easily taken swab cultures and those taken by biopsy was noted, especially in DFO. This was helpful for early change to appropriate treatment in cases where MDROs were isolated and empirical treatment was inappropriate. Further research is needed to confirm this observation in clinical practice.

Non-surgical therapy of diabetic foot infections based on recent guidelines and published data

Abstract Chronic, non-communicable diseases are affecting the lives of more and more people worldwide; due to obesity and inadequate eating habits, the proportion of diabetics is on an increasing trend globally. The development of a number of macro- and microangiopathic pathologies associated with the onset of diabetes affects the life expectancy of patients. Diabetic foot infection (DFI) is one of the most serious long-term complications of diabetes and may be considered an intersection of infectious and non-infectious diseases; these infections can significantly reduce the quality of life of affected patients. The purpose of this review was to summarize the latest recommendations for conservative (non-surgical) therapy for DFIs and diabetic foot osteomyelitis (DFO).

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

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). 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%). 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]). 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. NCT03615807; BASEC 2016-01008 (Switzerland).

Utility of Blood Parameters to Detect Complications during Long-Term Follow-Up in Patients with Diabetic Foot Osteomyelitis.

The evidence is still unclear regarding the role of blood parameters in detecting complications in patients who suffer from diabetic foot osteomyelitis (DFO). In this study, the aim was to identify the capacity of different blood parameters in the diagnosis and prediction of the onset of complications. A cross-sectional prospective study was carried out with 116 DFO patients. The following blood parameters were evaluated during 1 year of follow-up: leukocytes, neutrophils, lymphocytes, monocytes, eosinophils, basophils, erythrocyte sedimentation rate (ESR), glycemia, glycosylated hemoglobin, C-reactive protein (CRP), alkaline phosphatase, albumin, and creatinine. Complication events were assessed for each participant during the study period. We investigated the association between blood parameter values and the onset of complication events by conducting a receiver operating characteristic curve analysis. Eighty-five (73.3%) patients developed complications. Regarding blood parameters, higher values of lymphocytes and albumin were predictive factors at the 12-month follow-up once the ulcer had healed. Higher values of ESR had predictive and diagnostic value for the onset of complication events, and higher values of CRP and hyperglycemia were diagnostic factors since they were elevated during the occurrence of an event. In conclusion, after suffering from DFO, the elevation of lymphocytes, ESR, CRP, albumin, and glycemia could be useful in detecting and diagnosing patients who are likely to develop a complication. Serial blood tests are a useful tool for early detection by healthcare professionals to prevent complications.

Magnetic Resonance Imaging of Diabetic Foot Osteomyelitis: Imaging Accuracy in Biopsy-Proven Disease

Magnetic resonance imaging (MRI) is the recommended diagnostic imaging technique for diabetic foot osteomyelitis (DFO). The gold standard to diagnose osteomyelitis is bone biopsy with a positive culture and/or histopathology finding consistent with osteomyelitis. The purpose of this study is to assess the accuracy of MRI readings in biopsy-proven diabetic foot osteomyelitis with a second read done by a blinded, expert musculoskeletal radiologist. A retrospective chart review of 166 patients who received a bone biopsy to confirm the diagnosis of a suspected DFO at a large county hospital between 2010 and 2014. A second, blinded musculoskeletal radiologist reviewed the images for accuracy, once the official reading was recorded. Imaging results were correlated with the final diagnosis of osteomyelitis determined by bone biopsy. In 17 of 58 patients (29.3%), the diagnosis of DFO by MRI was not confirmed by bone biopsy. There were 12 false positives and 5 false negatives. After the second expert read, there were 5 false positives and 4 false negatives. The overall accuracy was 84% for the second read. Our study demonstrated results comparable to the previously reported meta-analysis findings. There is a clear variation on the read of MRI that could lead to an incorrect diagnosis of DFO. An integrated approach with evaluation of clinical findings, communication with radiologist about the MRI results when indicated, and bone biopsy is warranted for accurate diagnosis management of DFO.

Profile of Blood Glucose in Diabetic Patient Suffered from Diabetic Foot Osteomyelitis with Effective Low Carbohydrate Diet

The case was 52-year-old female with type 2 diabetes mellitus (T2DM) for 10-years. She complained of the decreased sensation of right lower foot, and revealed diabetic foot infection (DFI) and/or diabetic foot osteomyelitis (DFO) at right 1st proximal phalanx. Various data included body mass index (BMI) 33.3 kg/m2, HbA1c 11.4%, blood glucose 430 mg/dL, WBC 12100 /μL, C-reactive Protein (CRP) 13.5 mg/dL. On admission (day 1), she was started by 4 times of injection (Aspart and Glargin) with glucose profile 200-500 mg/dL. Surgical amputation of the right toe was performed between 1st metatarsal and proximal phalanx (day 17). Then, blood glucose profile decreased moderately. After discharge of the hospital, super-Low Carbohydrate Diet (LCD) was started without Aspart (day 37). Consequently, glucose profile was normalized with HbA1c 6.3% on (day 77). Consequently, LCD was evaluated to be effective for glucose variability in this case and some related discussion was described.

Percutaneous Bone Biopsy for Diabetic Foot Osteomyelitis: A Systematic Review and Meta-Analysis.

BackgroundDiabetes is the leading cause of lower extremity nontraumatic amputation globally, and diabetic foot osteomyelitis (DFO) is usually the terminal event before limb loss. Although guidelines recommend percutaneous bone biopsy (PBB) for microbiological diagnosis of DFO in several common scenarios, it is unclear how frequently PBBs yield positive cultures and whether they cause harm or improve outcomes.MethodsWe searched the PubMed, EMBASE, and Cochrane Trials databases for articles in any language published up to December 31, 2019, reporting the frequency of culture-positive PBBs. We calculated the pooled proportion of culture-positive PBBs using a random-effects meta-analysis model and reported on PBB-related adverse events, DFO outcomes, and antibiotic adjustment based on PBB culture results where available.ResultsAmong 861 articles, 11 studies met inclusion criteria and included 780 patients with 837 PBBs. Mean age ranged between 56.6 and 71.0 years old. The proportion of males ranged from 62% to 86%. All studies were longitudinal observational cohorts, and 10 were from Europe. The range of culture-positive PBBs was 56%–99%, and the pooled proportion of PBBs with a positive culture was 84% (95% confidence interval, 73%–91%). There was heterogeneity between studies and no consistency in definitions used to define adverse events. Impact of PBB on DFO outcomes or antibiotic management were seldom reported.ConclusionsThis meta-analysis suggests PBBs have a high yield of culture-positive results. However, this is an understudied topic, especially in low- and middle-income countries, and the current literature provides very limited data regarding procedure safety and impact on clinical outcomes or antibiotic management.

Analysis of the Composition and Functions of the Microbiome in Diabetic Foot Osteomyelitis Based on 16S rRNA and Metagenome Sequencing Technology

Metagenome sequencing has not been used in infected bone specimens. This prospective observational study explored the microbiome and its function in patients with diabetic foot osteomyelitis (DFO) and posttraumatic foot osteomyelitis (PFO) based on 16S rRNA sequencing and metagenome sequencing technologies. Spearman analysis was used to explore the correlation between dominant species and clinical indicators of patients with DFO. High-throughput sequencing showed that all the specimens were polymicrobial. The microbial diversity was significantly higher in the DFO group than in the PFO group. Firmicutes, Prevotellaceae, and Prevotella were the most abundant microbes in the DFO group. The most abundant microbes in the PFO group were Proteobacteria, Halomonadaceae, and Halomonas Prevotella denticola, Prevotella jejuni, and Prevotella fusca had positive correlation with the duration of diabetic foot infection (DFI_d). Proteus vulgaris was positively correlated with the infection index, while Bacteroides fragilis was negatively correlated. The microbial functional genes were more abundant in the DFO group than in the PFO group. Metagenome sequencing is feasible for the analysis of the microbiome in infected bone specimens. Gram-negative bacteria and anaerobes are dominant in DFO.

X-Ray Versus Magnetic Resonance Imaging in Diabetic Foot Osteomyelitis: A Clinical Comparison.

Radiographic imaging is an important diagnostic tool in diabetic foot osteomyelitis (DFO). It is unknown whether DFO cases diagnosed with conventional X-ray versus positive Magnetic Resonance Imaging (MRI) differ regarding epidemiology and treatment outcome. Theoretically, signs of inflammation on MRI without bone lesions might be easier to treat. Our clinical pathway for diabetic foot infections discourages the use of MRI for the diagnosis of DFO. We compared the epidemiology and therapy of non-amputated DFO with positive features on conventional X-ray, MRI, or both. Radiology specialists interpreted the images. The intraoperative aspect of bone during amputation and the results of bone cultures were considered the gold standard for DFO diagnosis. We prospectively followed 390 DFO episodes in 186 adult patients for a median of 2.9 years and performed 318 conventional X-rays (median costs 100 Swiss Francs; 100 US$) and 47 (47/390; 12%) MRI scans (median 800 Swiss Francs; 800 US $). Among them, 18 episodes were associated with positive MRI findings but lacked bone lesions on X-ray. After debridement, the median duration of systemic antibiotics was 28 days for MRI-only episodes and 30 days for X-ray-positive cases (Wilcoxonranksum- test; p=0.26). The corresponding median numbers of surgical debridements were 1 and 1; and recurrence was witnessed in 25% and 28%, respectively. In multivariate logistic regression analysis, MRI-only episodes did not alter the remission rate (odds ratio 0.5, 95%CI 0.1-5.2). According to our clinical pathway, DFO episodes with positive MRI findings only did not differ epidemiologically from the remaining DFO cases and did not influence the choice of therapy nor remission rate.

Multidrug resistant organism predicts ulcer recurrence following surgical management of diabetic foot osteomyelitis.

Diabetic foot ulcers commonly precede diabetic foot osteomyelitis (DFO) and once the latter occurs, surgical management is often performed. The presence of osteomyelitis is an independent risk factor for the development of re-ulceration. We investigated the relationship between causative organisms in osteomyelitis and 1-year diabetic foot outcomes (re-ulceration, amputation, and death) following surgical management in an observational cohort of 223 patients. Univariate and multivariate analyses were performed for available demographic, clinical, and laboratory data. In addition, random forest plots were used to identify microbiologic predictors of 1-year outcomes. Patients with osteomyelitis managed surgically were younger and exhibited more painful peripheral neuropathy than outpatients with diabetes alone (both P < .0001). Osteomyelitis proximal margin cultures were diverse, at times polymicrobial, and included multidrug-resistant organisms in 13.9% of the cohort. In patients who underwent surgery, 44.5% experienced a re-ulceration on the same foot within 12 months of surgery. The presence of multidrug-resistant organisms on proximal bone culture was found to be a significant predictor of diabetic foot ulcer recurrence in univariate modelling (P < .001) and importance rankings. This is the first study to use prediction modelling to identify a relationship between multidrug-resistant organisms and diabetic foot ulcer recurrence following DFO.

Recent Topics on Various Clinical Problems Related with Diabetic Neuropathy

Diabetes has been a crucial disease worldwide, and authors have continued diabetic practice and research. Recent topics on neuropathy are described. For diabetic patients, common symptoms of dysesthesia and loss of protective sensation (LOPS) should be checked annually. Diabetic peripheral neuropathy (DPN) has been treated by pregabalin, duloxetine, gabapentin and tapentadol. Autonomic Neuropathy (AN) includes Orthostatic Hypotension (OH), Cardiac Autonomic Neuropathy (CAN), gastroparesis and genitourinary disturbances. Diabetic foot may be related with Peripheral Arterial Disease (PAD), Diabetic Foot Infection (DFI), diabetic foot osteomyelitis (DFO) and amputation. For those, Hyperbaric Oxygen Therapy (HBOT) may be effective with continuing discussion.

Combined Effects of Single Nucleotide Polymorphisms (SNPs) within C-reactive Protein (CRP) and Environmental Parameters on Risk and Prognosis for Diabetic Foot Osteomyelitis Patients.

This study was aimed to discover the combined effects of single nucleotide polymorphisms (SNPs) within the C-reactive protein (CRP) gene and potential environmental factors on the risk and prognosis for diabetic foot osteomyelitis (DFO). A total of 1734 diabetes mellitus patients, 681 with DFO and 1053 without DFO, were successfully recruited, as well as 1261 healthy control individuals. Participants data were recorded regarding age, gender, smoking and drinking history, body mass index (BMI), hypertension, cacosmia, and ulceration. A total of 11 SNPs within the CRP gene were designated for exploration, by logistic regression analyses, of how they might interact with environmental factors to affect susceptibility to DFO. Frequencies of smoking and drinking, and incidence of hypertension, cacosmia, or ulceration displayed marked differences (all P<0.05) between DFO and non-DFO patients. Furthermore, allele G of rs11265260 (A>G), allele G of rs1800947 (C>G), and allele T of rs3093059 (T>C) and rs1130864 (C>T) exhibited a trend to increase risk of DFO (all P<0.05). Allele G of rs11265260 (A>G), allele G of rs1800947 (C>G) and rs3093068 (G>C), and allele T of rs1130864 (C>T) were significant predictors of poor prognosis among DFO patients (P<0.05). In addition, genotypes of rs11265260 (i.e., GG and AG), rs1800947 (i.e., CG and GG), rs3093059 (i.e., TT) and rs113084 (i.e., CT and TT) amplified the influence of smoking, alcohol consumption, cacosmia, and ulceration on progression from non-DFO to DFO (all γ>1). Genetic mutations within CRP functioned interactively with external factors to affect DFO risk.

Erythrocyte Sedimentation Rate Combined With the Probe-to-Bone Test for Fast and Early Diagnosis of Diabetic Foot Osteomyelitis.

This study aimed to investigate the erythrocyte sedimentation rate (ESR) optimal cutoff point in Chinese patients with diabetic foot osteomyelitis (DFO) and to evaluate the screening value of ESR combined with probe-to-bone (PTB) test for a fast diagnosis of DFO in early stage. A total of 204 diabetic inpatients with foot infection were tested for white blood cell count, neutrophil %, C reactive protein, and ESR at admission within 24 hours. All patients were performed PTB test. Patients with DFO (111) were confirmed by bone biopsy, the other patients (86) had only soft tissue infection. Although white blood cell count, neutrophil %, C-reactive protein, and ESR were different between the 2 groups, only area under curve of ESR was 0.832, with the value as a diagnostic indicator. The best cut point of ESR was >43 mm/h; the sensitivity, specificity, positive predictive value (+PV), and negative predictive value (-PV) were 82.9%, 70.5%, 0.78, and 0.77, respectively. ESR combined with PTB test (serial test), the sensitivity, specificity, +PV, -PV, positive likelihood ratio (+LR), and negative LR (-LR) were 63.56%, 98%, 0.97, 0.67, 31.75, and 0.37, respectively. ESR combined with PTB test (parallel test), the sensitivity, specificity, +PV, -PV, +LR, and -LR were 96%, 65.7%, 0.78, 093, 2.8, and 0.06, respectively, combined with PTB test is simple, favorable for application, and can early fast screening patients with DFO in high-risk patients.

Adjunctive rifampin therapy for diabetic foot osteomyelitis: A protocol for systematic review and meta-analysis.

The prevalence of diabetes continues to rise around the world. Diabetic foot is a serious complication of diabetes, and diabetic patients with diabetic foot osteomyelitis (DFO) have a fourfold increased risk of amputation, usually indicating death. Therefore, it is particularly important to seek a more effective treatment for DFO. The treatment of DFO varies from person to person, and antimicrobial therapies vary widely. A large number of clinical studies have shown that rifampicin adjuvant therapy can reduce the rate of amputation and mortality in DFO patients. However, there is no systematic summary of clinical evidence, which limits the clinical application of rifampicin. Therefore, we attempted to provide high-quality evidence for the clinical efficacy and safety of rifampin in the adjuvant treatment of DFO through this meta-analysis. English literature is mainly searched in Cochrane Library, PubMed, EMBASE and Web of Science, while Chinese literature is from CNKI, CBM, VIP and Wangfang databases. At the same time, we will search clinical registration tests and gray literature. Two methodologically trained researchers will read the title, abstract, and full text, and independently select qualified literature based on inclusion and exclusion criteria. Binary data is expressed as relative risk, continuous data is expressed as mean difference or standard mean difference. The final data are synthesized using a fixed effect model or a random effect model, depending on the presence of heterogeneity. In the end, the patient's amputation rate and mortality were the main research indicators. Survival rate, HbA1c, serum creatinine, changes in ulcer area, and SF-36 quality of life assessment were used as secondary indicators. We will perform a sensitivity analysis to assess the stability of the results. Then the publication bias was evaluated by funnel plot analysis and Egger test. Finally, we will use a "recommendation grading, evaluation, formulation and evaluation" system to assess the quality of the evidence. All data analysis will be meta-analyzed by the statistical software RevMan software version 5.3. This study will provide a high-quality comprehensive report on the effectiveness and safety of rifampicin in the treatment of DFO, and our findings will be published in peer-reviewed journals. This systematic review and meta-analysis will provide a comprehensive summary and careful evaluation of rifampicin as an adjuvant treatment of DFO with a view to providing multiple options for clinical treatment of the disease. REGISTRATION NUMBER:: is INPLASY202040084.

Distribution characteristics of pathogen and antibiotic susceptibility in diabetic foot osteomyelitis

Objective To retrospectively analyze distribution characteristics of pathogenic bacteria and their antimicrobial susceptibility in patients with diabetic foot osteomyelitis(DFO). Methods Sixty cases of suspected DFO were collected from the Endocrinology Department of Henan Provincial People′s Hospital. After admission, bone biopsy was carried out to confirm the pathological diagnosis, and the pathogenic bacteria and drug sensitivity were determined by bone culture. In addition, bacterial culture was carried out in the basal tissue of the wound, and the results of bacterial culture were compared with those of bone culture. Results Sixty patients were diagnosed as DFO after bone biopsy. Among the 60 patients, 45 patients underwent bone culture and basal tissue culture. There are 24 patients of whom the results were consistent, accounting for 53.3%. The positive rate of bone culture was 55.0%, there were 16 strains of gram-positive bacteria and 22 strains of gram-negative bacteria. Staphylococcus aureus(9 strains) occurrence was the most, common finding, followed by Escherichia coli(6 strains). The course of diabetic foot, albumin(ALB), and antibiotic usage rate before admission were lower in bone culture positive group than those in bone culture negative group, while white blood cell(WBC) and C-reactive protein(CRP) were higher in bone culture negative group(P 0.05). The results of bone culture showed that Staphylococcus aureus was the main Gram-positive bacteria, which was more sensitive to vancomycin, tigecyclin, linezolid, etc. Escherichia coli was the main Gram-negative bacteria, which was more sensitive to tigecyclin, carbapenems, amikacin, etc. Conclusion Bone biopsy and bone culture should be carried out in cases for suspected DFO patients to identify the pathogenic bacteria, and the bone tissue should be preserved and obtained according to the operation specification before the application of antibiotics, and the appropriate antibiotics should be selected according to the drug sensitivity results. Key words: Diabetic foot osteomyelitis; Bone biopsy; Bone culture; Basal tissue culture; Pathogen; Antibiotics

Feasibility of Percutaneous Bone Biopsy as Part of the Management of Diabetic Foot Osteomyelitis in a 100% Neuropathic, Grade 3 IDSA/IWGDF Population on an Outpatient Basis.

The present study aimed to evaluate the feasibility of percutaneous bone biopsy in an ambulatory setting as part of the management of diabetic foot osteomyelitis (DFO) on an outpatient basis. DFO may complicate some cases of apparently nonsevere foot infections in patients with diabetes and greatly increase the risk of a lower extremity amputation. It has been suggested that bone culture-based antibiotic therapy is a predictive factor of success in patients with diabetes treated nonsurgically for osteomyelitis of the foot. It is recommended to identify the causative microorganism(s) by the means of either a surgical or percutaneous bone biopsy taken appropriately to select the proper antibiotic therapy. Percutaneous bone biopsy in patients not requiring surgery is, however, not performed in everyday practice as it should be according to the current recommendations. In the present retrospective study, we report a series of 23 consecutive patients with a suspicion of DFO in whom 28 bone samples were collected by percutaneous biopsy at the bedside in an outpatient setting. The percentage of positive cultures was in accordance with that reported in the literature. The mean number of isolates per specimen was 1.04. After a mean 12-month follow-up, the remission was almost of 78%. No adverse event related to the bone biopsy was noted. After a 1-year follow-up, no recurrence was recorded among the patients in remission. The results of the present study suggest that bedside percutaneous bone biopsy performed in the ambulatory setting is a valuable and safe tool in the management of DFO on an outpatient basis.

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.

A multicenter randomized placebo controlled trial of rifampin to reduce pedal amputations for osteomyelitis in veterans with diabetes (VA INTREPID)

BackgroundThe prevalence of diabetes mellitus continues to inexorably rise in the United States and throughout the world. Lower limb amputations are a devastating comorbid complication of diabetes mellitus. Osteomyelitis increases the risk of amputation fourfold and commonly presages death.Antimicrobial therapy for diabetic foot osteomyelitis (DFO) varies greatly, indicating that high quality data are needed to inform clinical decision making. Several small trials have indicated that the addition of rifampin to backbone antimicrobial regimens for osteomyelitis outside the setting of the diabetic foot results in 28 to 42% higher cure rates.Methods/designThis is a prospective, randomized, double-blind investigation of the addition of 6 weeks of rifampin, 600 mg daily, vs. matched placebo (riboflavin) to standard-of-care, backbone antimicrobial therapy for DFO. The study population are patients enrolled in Veteran Health Administration (VHA), ages ≥18 and ≤ 89 years with diabetes mellitus and definite or probable osteomyelitis of the foot for whom an extended course of oral or intravenous antibiotics is planned. The primary endpoint is amputation-free survival. The primary hypothesis is that using rifampin as adjunctive therapy will lower the hazard rate compared with the group that does not use rifampin as adjunctive therapy. The primary hypothesis will be tested by means of a two-sided log-rank test with a 5% significance level. The test has 90% power to detect a hazard ratio of 0.67 or lower with a total of 880 study participants followed on average for 1.8 years.DiscussionVA INTREPID will test if a rifampin-adjunctive antibiotic regimen increases amputation-free survival in patients seeking care in the VHA with DFO. A positive finding and its adoption by clinicians would reduce lower extremity amputations and their associated physical and emotional impact and reduce mortality for Veterans and for the general population with diabetic foot osteomyelitis. Given that rifampin-adjunctive regimens are currently employed for therapy for the majority of DFO cases in Europe, and only in a small minority of cases in the United States, the trial results will impact therapeutic decisions, even if the null hypothesis is not rejected.Trial registrationRegistered January 6, 2017 at ClinicalTrials.gov, NCT03012529.