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To investigate risk factors for re-infection and compare the outcomes in people with diabetic foot infections. A retrospective chart review was conducted, and 294 hospitalised patients with moderate to severe diabetic foot infections (DFIs) were analysed for this study. The diagnosis and classification of the severity of infection was based on the International Working Group on the Diabetic Foot (IWGDF) infection guidelines. Skin and soft tissue infections were diagnosed based on clinical observations as per IWGDF classification in addition to ruling out any suspected osteomyelitis (OM) through negative bone culture, MRI or WBC SPECT CT. OM was confirmed by bone culture or histopathology. Clinical outcomes were based on a 12-month follow-up period. All dichotomous outcomes were compared using χ 2 with an alpha of 0.05. The result of this study shows a 48% rate of re-infection in people admitted to our hospital with moderate and severe diabetic foot infections (DFI). Patients with osteomyelitis present during the index admission were 2.1 times more likely to experience a re-infection than patients with soft tissue infection (56.7% vs. 38.0% respectively). In the univariate analysis, risk factors for re-infection included osteomyelitis, non-healing wounds, prolonged wound healing, antidepressants and leukocytosis. In the regression analysis, the only risk factor for re-infection was wounds that were not healed >90 days (HR =2.0, CI: 1.5, 2.7, p = 0.001). Re-infection is very common in patients with moderate and severe diabetic foot infections. Risk factors include osteomyelitis, non-healing wound, prolonged wound healing, antidepressants and leukocytosis., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

The objective of the study was to compare outcomes in patients with complete surgical resection versus partial resection of diabetic foot osteomyelitis (OM). A post hoc analysis of 171 patients with OM was performed using data from two randomized clinical trials. OM was confirmed with bone culture or histopathology. Surgical culture specimens were obtained from resected bone and sent for histopathology and microbiology. Residual osteomyelitis (RO) was defined as a positive resected margin on culture or histopathology. No residual osteomyelitis (NRO) was defined as no growth from bone culture and no histopathological inflammation in the biopsy of the resection margin. Data from the 12-month follow-up were used to determine clinical outcomes. During the index hospitalization, NRO patients had significantly shorter duration of antibiotic therapy (NRO 21.0, 13.0-38.0 vs. RO 37.0, 20.8-50.0, p <0.01) and more amputations than patients with RO (NRO 89.9% vs. RO 60.9%, p <0.01). During the 12-month follow-up, patients with NRO also had significantly shorter duration of antibiotic therapy (NRO 42, 21.0-66.5 vs. RO 50.5, 35.0-75.0, p = 0.02). During the 12-month follow-up, there was no difference in ulceration at the same site (NRO 3.7%, RO 4.3% p = 0.85), hospitalization (NRO 32.6%, RO 34.8%, p = 0.76), total re-infections (NRO 25.3%, RO 29.3%, p = 0.56), re-infection with osteomyelitis (NRO 13.3% vs. 13.5%, p = 0.36), amputation (NRO 8.8%, RO 5.4%, p = 0.86) and time to wound healing in days (NRO 94, 41.0-365 vs. RO 106, 42.8-365, p = 0.77). Successful treatment of osteomyelitis was achieved by 86.7% and 86.5% of patients. During the index hospitalization, patients with no residual osteomyelitis had more amputations and were treated with antibiotics for a shorter duration. During the 12-month follow-up, patients with no residual osteomyelitis had shorter durations of antibiotics. There were no differences in re-infection, amputation, re-ulceration or hospitalization. Level of evidence: 1., (© 2024 The Author(s). International Wound Journal published by Medicalhelplines.com Inc and John Wiley & Sons Ltd.)

Background: To compare pathogens involved in skin and soft-tissue infections (SSTIs) and pedal osteomyelitis (OM) in patients with and without diabetes with puncture wounds to the foot., Methods: We evaluated 113 consecutive patients between June 1, 2011, and March 31, 2019, with foot infection (SSTIs and OM) from a puncture injury sustained to the foot. Eighty-three patients had diabetes and 30 did not. We evaluated the bacterial pathogens in patients with SSTIs and pedal OM., Results: Polymicrobial infections were more common in patients with diabetes mellitus (83.1% versus 53.3%; P = .001). The most common pathogen for SSTIs and OM in patients with diabetes was Staphylococcus aureus (SSTIs, 50.7%; OM, 32.3%), whereas in patients without diabetes it was Pseudomonas (25%) for SSTIs. Anaerobes (9.4%) and fungal infection (3.1%) were uncommon. Pseudomonas aeruginosa was identified in only 5.8% of people with diabetes., Conclusions: The most common bacterial pathogen in both SSTIs and pedal OM was S aureus in patients with diabetes. Pseudomonas species was the most common pathogen in people without diabetes with SSTIs.

Severe diabetic foot infections (DFI) are both limb threatening and life threatening and associated with negative impact on health-related quality of life. Most severe DFIs require surgical intervention, and the goal of treatment should be preservation of limb function in addition to eradication of infection. Minor amputations are required in approximately 40% and major amputations in approximately 20% of patients. Significant risk factors for lower extremity amputation included male gender, smoking, previous amputation, osteomyelitis, peripheral artery disease, retinopathy, severe infections, gangrene, neuroischemic diabetic foot infections, leukocytosis, positive wound cultures, and isolation of gram-negative bacteria., Competing Interests: Disclosure D.K. Wukich is a consultant for Orthofix and Stryker Wright Medical, receives royalties from Arthrex, an Executive Board Member and President, International Association of Diabetic Foot Surgeons and a member of the Scientific Advisory Board for Advanced Oxygen Therapy, Inc. K.M. Raspovic is a consultant for Orthofix. M.J. Johnson has nothing to disclose., (Copyright © 2022 Elsevier Inc. All rights reserved.)

Objective: To investigate the predictive value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) in persons with and without diabetes with osteomyelitis (OM)., Methods: We evaluated 455 patients in a retrospective cohort study of patients admitted to the hospital with diabetic foot OM (n = 177), diabetic foot soft-tissue infections (STIs) (n = 176), nondiabetic OM (n = 51), and nondiabetic STIs (n = 51). Infection diagnosis was determined through bone culture, histopathologic examination for OM, and/or imaging (magnetic resonance imaging/single-photon emission computed tomography) for STI. The optimal cutoff values of ESR and CRP in predicting OM were determined by receiver operating characteristic curve analysis. Sensitivity, specificity, positive and negative predictive values, and positive and negative likelihood ratios were determined through contingency tables., Results: In persons without diabetes with STI or OM, the mean ESR and CRP differences were 10.0 mm/h and 2.6 mg/dL, respectively. In contrast, persons with diabetes had higher levels of each: 24.8 mm/h and 6.8 mg/dL, respectively. As a result, ESR and CRP predicted OM better in patients with diabetes. However, when patients were stratified by neuropathy status, ESR remained predictive of OM in diabetic patients with neuropathy (75% sensitivity, 58% specificity) but not in diabetic patients without neuropathy (50% sensitivity, 44% specificity). Also, CRP remained predictive irrespective of neuropathy status. A similar trend was observed in patients without diabetes., Conclusions: Previous studies have reported that ESR and CRP are predictive of OM. However, this study suggests that neuropathy influences the predictive value of inflammatory biomarkers. The underlying mechanisms require further study.

The aim of this study was to report clinical outcomes of moderate and severe foot infections in patients without diabetes. Medical records of 88 nondiabetic patients with foot infections treated at a safety net hospital were retrospectively reviewed. Patients were grouped by the presence of soft-tissue infection (STI) or osteomyelitis (OM). The diagnosis of OM was determined by positive bone culture or histopathology. STIs were defined by negative bone biopsy or negative imaging with magnetic resonance imaging or computed tomography/dual-modality radiolabeled white blood cell single-photon emission computed tomography. Patient outcomes were recorded ≤1 year after admission. Eighty-eight nondiabetic patients admitted to our institution for moderate or severe foot infections were included, 45 OM and 43 STI. No differences were noted in patient characteristics except that OM patients had a higher prevalence of neuropathy (66.7% versus 39.5%, p = .02). OM patients required surgery more often (97.8% versus 67.4%, p < .01), a greater number of surgeries (2.0 ± 1.2 versus 1.4 ± 1.3, p = .02), and more amputations (75.6% versus 11.6%, p < .01) than STI patients. OM patients had a higher proportion of wounds that healed (82.2% versus 62.8%, p = .04). There were no significant differences in reinfection (35.6% versus 25.6%, p = .36), foot-related readmission to hospital (35.6% versus 23.3%, p = .25), or total duration of antibiotics (13.9 ± 10.2 versus 13.5 ± 12.9, p = .87) between OM and STI patients. In conclusion, OM patients required more surgeries and amputations than patients with STIs; however, they had similar rates of reinfection and readmission within a year after the index hospitalization., (Copyright © 2020 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: We provide evidence to revise the Infectious Diseases Society of America (IDSA) diabetic foot infection classification by adding a separate tier for osteomyelitis and evaluating if moderate and severe infection criteria improve the classification's ability to direct therapy and determine outcomes., Methods: We retrospectively evaluated 294 patients with moderate and severe infections. Osteomyelitis was confirmed by bone culture or histopathology. Soft tissue infection (STI) was based on negative bone culture, magnetic resonance imaging, or single-photon emission computed tomography. We stratified STI and osteomyelitis using IDSA criteria for moderate and severe infections and compared outcomes and complications., Results: Osteomyelitis patients had greater antibiotic duration (32.5 ± 46.8 vs 63.8 ± 55.1 days; P < .01), surgery frequency (55.5% vs 99.4%; P < .01), number of surgeries (2.1 ± 1.3 vs 3.3 ± 2.3; P < .01), amputations (26.3% vs 83.4%; P < .01), reinfection (38.0% vs 56.7%; P < .01), and length of stay (14.5 ± 14.9 vs 22.6 ± 19.0 days; P < .01). There were no differences in moderate and severe STI outcomes except for infection readmissions (46.2% vs 25.0%; P = .02), and acute kidney injury (31.2% vs 50.0%; P = .03). There were no differences in moderate and severe osteomyelitis except the number of surgeries (2.8 ± 2.1 vs 4.1 ± 2.5; P < .01) and length of stay (18.6 ± 17.5 vs 28.2 ± 17.7; P < .01)., Conclusions: The IDSA classification better reflects outcomes if risk categories are stratified by STI or osteomyelitis and moderate and severe infections are not categorized separately., (© The Author(s) 2019. Published by Oxford University Press for the Infectious Diseases Society of America. All rights reserved. For permissions, e-mail: journals.permissions@oup.com.)

Objective: The aim of this meta-analysis is to evaluate the effect of withholding antibiotics prior to obtaining a bone biopsy in the diagnosis of osteomyelitis., Methods: Literature searches on Scopus, PubMed, and Google Scholar were performed with the input antibiotic, bone, biopsy, osteomyelitis, and prior both separately and together, though initially as a combination, as key words for all study types in the English language published up until July 2018. The initial combination search (and subsequent additional search of the references) yielded 924 related articles, which ultimately resulted in 12 articles with adequate data for analysis. Data were analyzed using an inverse variance method to determine the weight of the studies in a random effects model, pooling the data for odds ratios (OR) and heterogeneity. Bias risk was determined with the Quality Assessment of Diagnostic Accuracy Studies 2 system., Results: Of the 12 studies, 8 failed to demonstrate that antibiotics administered prior to bone biopsy have an effect on culture yield, while 4 reported a significant effect on culture yield. The total weighted OR for all studies was 2.02 (95% confidence interval [CI], 0.94-4.36; P = .04) and the prediction interval was 0.17-23.63. When vertebral osteomyelitis (VO) and nonvertebral osteomyelitis (NVO) articles were evaluated separately, the VO OR was 2.95 (95% CI, 1.40-6.24) and the prediction interval was 0.40-21.53. The OR for NVO was 0.66 (95% CI, 0.04-12.03) and the prediction interval was 0-114.53., Conclusions: When all studies as well as when NVO studies only were evaluated, there was no significant difference in bacterial pathogen yield based on antibiotic exposure. When VO studies were evaluated separately, there were fewer pathogens recovered than when antibiotics were administered prior to obtaining bone cultures.

Background: Distinguishing osteomyelitis from soft-tissue infection of the foot is important because osteomyelitis is associated with more operations, amputation, and prolonged antibiotic exposure. Both erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) are routinely ordered inflammatory biomarkers for evaluating foot infection. When initial evaluation is inconclusive, advanced imaging is indicated, and high clinical or radiographic suspicion of osteomyelitis may indicate bone biopsy to identify organisms and antibiotic sensitivity. Although ESR and CRP levels are helpful for distinguishing osteomyelitis from soft-tissue infections in patients with diabetes-related foot infections, parameters regarding optimal cutoff values for those tests have not, to our knowledge, been defined., Questions/purposes: (1) What are the optimal cutoff values for ESR and CRP to differentiate osteomyelitis from soft-tissue infection in patients with diabetes-related foot infection? (2) Can a diagnostic algorithm be derived to guide interpretation of ESR and CRP to improve recognition of osteomyelitis in the setting of diabetic foot infection?, Methods: The medical records of 1842 patients between 18 and 89 years of age treated at our institution between January 1, 2010 and February 6, 2017 for foot infection were reviewed. For inclusion, patients must have had a diagnosis of diabetes mellitus, moderate or severe infection, ESR and CRP values within 72 hours of admission, either advanced imaging (MRI or single-positron emission computed tomography/computed tomography [SPECT/CT]) or bone biopsy during admission and must not have had comorbidities that could affect ESR and CRP, such as autoimmune disorders. As such, 1489 patients were excluded, and 353 patients were included in the study. Osteomyelitis was diagnosed by positive bone culture or histopathology. Osteomyelitis was considered to be absent if there was a negative MRI or SPECT/CT result, or negative bone culture and histology findings if imaging was inconclusive. We identified 176 patients with osteomyelitis and 177 with soft-tissue infection. A blinded investigator performed the statistics. Optimal cutoffs of ESR and CRP were determined using receiver operative characteristic (ROC) analysis. A diagnostic algorithm was determined using epidemiologic principles of screening evaluations., Results: An ESR of 60 mm/h and a CRP level of 7.9 mg/dL were determined to be the optimal cutoff points for predicting osteomyelitis based on results of the ROC analysis. The ESR threshold of 60 mm/h demonstrated a sensitivity of 74% (95% confidence interval [CI], 67-80) and specificity of 56% (95% CI, 48-63) for osteomyelitis, whereas the CRP threshold of 7.9 mg/dL had a sensitivity of 49% (95% CI, 41-57) and specificity of 80% (95% CI, 74-86). If the ESR is < 30 mm/h, the likelihood of osteomyelitis is low. However, if ESR is > 60 mm/h and CRP level is > 7.9 mg/dL, the likelihood of osteomyelitis is high, and treatment of suspected osteomyelitis should be strongly considered., Conclusions: While ESR is better for ruling out osteomyelitis initially, CRP helps distinguish osteomyelitis from soft-tissue infection in patients with high ESR values. Further prospective studies addressing the prognostic value of ESR and CRP are needed, and a more comprehensive diagnostic algorithm should be developed to include other diagnostic tests such as probe-to-bone and imaging., Level of Evidence: Level III, diagnostic study.

The aim of the study was to assess the diagnostic value of erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) levels in differentiating foot osteomyelitis (OM) from soft tissue infection (STI) in persons without diabetes. We evaluated 102 patients in a retrospective cohort study of nondiabetic patients admitted to our institution with OM (n = 51) and with STI (n = 51). Patient diagnosis was determined through bone culture and/or histopathology for OM and magnetic resonance scan and/or single-photon emission computed tomography for STI. Cutoffs for ESR and CRP to predict OM as identified by receiver operating characteristic were 45.5 mm/h and 3.45 mg/dL, respectively. The ESR cutoff demonstrated a sensitivity and specificity of 49% and 79%, while the values for CRP were 45% and 71%, respectively. The combined sensitivity and specificity for ESR and CRP were 33% and 84%. The positive and negative predictive values were 68% and 60% for ESR and 61% and 56% for CRP, respectively. In conclusion, ESR and CRP demonstrate poor sensitivity and specificity for detecting OM in the nondiabetic foot. These markers have little diagnostic utility in the nondiabetic foot., (Copyright © 2018 the American College of Foot and Ankle Surgeons. Published by Elsevier Inc. All rights reserved.)

Background: This study was conducted to evaluate the outcomes of patients with diabetic foot osteomyelitis (DFO) compared to diabetic foot soft tissue infections (STIs)., Methods: 229 patients who were hospitalized with foot infections were retrospectively reviewed, identifying 155 patients with DFO and 74 patients with STI. Primary outcomes evaluated were the rates of amputations and length of hospital stay. DFO was confirmed by the presence of positive bone culture and/or histopathology., Results: Patients with DFO had a 5.6 times higher likelihood of overall amputation (P < .0001), a 3.4 times higher likelihood of major amputation (P = .027) and a 4.2 times higher likelihood of minor amputation (P < .0001) compared to patients without DFO. Major amputation was performed in 16.7% patients diagnosed with DFO and 5.3% of patients diagnosed with STI. Patients with DFO complicated by Charcot neuroarthropathy had a 7 times higher likelihood of undergoing major amputation (odds ratio 6.78, 95% confidence interval 2.70-17.01, P < .0001). The mean hospital stay was 7 days in DFO and 6 days in patients with DFI (P = .0082). Patients with DFO had a higher erythrocyte sedimentation rate (85 vs 71, P = .02) than patients with STI, however the differences in C-reactive protein (13.4 vs 11.8, P = .29) were not significantly different., Conclusion: In this study of moderate and severe DFIs, the presence of osteomyelitis resulted in a higher likelihood of amputation and longer hospital stay. Readers should recognize that the findings of this study may not be applicable to less severe cases of DFO that can be effectively managed in an outpatient setting., Level of Evidence: Level III, retrospective comparative case series., (© The Author(s) 2016.)

Unlabelled: Squamous cell carcinoma is one of the most common human malignancies; however, it is uncommon in the lower extremity. These lesions require prompt surgical attention and a delay in diagnosis can be harmful to the patient. We present a case report of squamous cell carcinoma with chronic osteomyelitis in a patient without diabetes. Definitive treatment included a transtibial amputation and metastatic workup was negative for active malignancy. Surgeons who treat chronic wounds should be cognizant of the potential for malignant degeneration., Level of Evidence: Therapeutic, Level IV: Case report., (© 2015 The Author(s).)

Aims: Lower-extremity amputation in patients with diabetes is associated with premature mortality and impaired ambulatory status. Despite advances in limb salvage techniques, certain patients will require major amputation. The hypothesis of this study is that self-reported outcomes of patients with non-reconstructable Charcot neuroarthropathy and chronic osteomyelitis improve after trans-tibial amputation., Methods: Self-reported outcome was assessed using the Medical Outcome Study Short Form 36-item health survey (SF-36) and the Foot and Ankle Ability Measure. The study group included 13 patients with diabetes who underwent a trans-tibial amputation and completed both the Medical Outcome Study SF-36 and the Foot and Ankle Measure pre- and post-operatively., Results: Significant improvement after trans-tibial amputation occurred in the SF-36 Physical Component Summary score and both the Foot and Ankle Measure Activity of Daily Living and Sports scores at a mean follow-up of 79 weeks (range 53-122 weeks). Although the SF-36 Mental Component Summary score improved, the improvement did not achieve statistical significance (P = 0.30). Twelve of the 13 patients were satisfied with the amputation and had no reservations., Conclusions: In a select group of Charcot neuroarthropathy patients with chronic osteomyelitis, trans-tibial amputation resulted in improvement in self-reported outcomes. Although major lower-extremity amputation is a devastating complication in patients with diabetes, the results of this study provides some evidence for optimism in these high-risk patients., (© 2012 The Authors. Diabetic Medicine © 2012 Diabetes UK.)

Scintigraphy with indium-labeled white blood cells has been reported to be sensitive and specific in the diagnosis of low-grade sepsis of the musculoskeletal system. We reviewed the records of fifty patients who had suspected osteomyelitis or suspected infection about a total joint prosthesis and who underwent scintigraphy with technetium-99m methylene diphosphonate and scintigraphy with indium-111 oxine-labeled white blood cells before an open surgical procedure. Any patient who received preoperative antibiotics was not included in the study. For all of the patients, gram-stain examination of smears, evaluation of a culture of material from the operative site, and histological examination were done. The patients were divided into two groups. Group I was composed of twenty-four patients, each of whom had a prosthesis in place and complained of pain. Group II was composed of twenty-six patients for whom a diagnosis of chronic osteomyelitis had to be considered. With the indium scans alone, there was only one false-negative result (in Group II), but there were eighteen false-positive results (eight patients in Group II and ten patients in Group I). Although scintigraphy with indium-labeled white blood cells is quite sensitive, it is not specific in detecting chronic osteomyelitis; a negative scan should be considered highly suggestive that osteomyelitis is not present. Specificity can be increased by interpreting the indium scan in conjunction with the technetium scan.

The cases of six patients with suspected osteomyelitis of the axial skeleton who underwent preoperative indium-labeled white blood cell scintigraphy (In-WBC) were reviewed retrospectively. Five of these patients had undergone previous spinal surgery, and all six patients complained of back pain. Four of these six patients were proven to have osteomyelitis by culture and histopathology. The sensitivity, specificity, and accuracy of In-WBC scintigraphy in detecting osteomyelitis of the axial skeleton was 25%, 50%, and 33%, respectively. Our preliminary experience in six patients with suspected osteomyelitis of the axial skeleton suggests that In-WBC scintigraphy is neither sensitive nor specific in predicting infection.