• 1. 

    Lipsky BA, Berendt AR & Cornia PB et al.; Infectious Diseases Society of America: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54: e132, 2012.

    • Crossref
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  • 2. 

    Lipsky BA, Aragon-Sanchez J & Diggle M et al.; International Working Group on the Diabetic Foot: IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev 32 (suppl 1): 45, 2016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. 

    Vouillarmet J, Moret M & Morelec I et al.: Application of white blood cell SPECT/CT to predict remission after a 6 or 12 week course of antibiotic treatment for diabetic foot osteomyelitis. Diabetologia 60: 2486, 2017.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4. 

    Lazaga F, Van Asten SA & Nichols A et al.: Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in diabetic foot osteomyelitis. Int Wound J 13: 1158, 2016.

  • 5. 

    Vouillarmet J, Morelec I & Thivolet C: Assessing diabetic foot osteomyelitis remission with white blood cell SPECT/CT imaging. Diabet Med 31: 1093, 2014.

  • 6. 

    Richard JL, Lavigne JP & Got I et al.: Management of patients hospitalized for diabetic foot infection: results of the French OPIDIA study. Diabetes Metab 37: 208, 2011.

  • 7. 

    Senneville E, Lombart A & Beltrand E et al.: Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care 31: 637, 2008.

  • 8. 

    Senneville E, Yazdanpanah Y & Cazaubiel M et al.: Rifampicin-ofloxacin oral regimen for the treatment of mild to moderate diabetic foot osteomyelitis. J Antimicrob Chemother 48: 927, 2001.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9. 

    Embil JM, Rose G & Trepman E et al.: Oral antimicrobial therapy for diabetic foot osteomyelitis. Foot Ankle Int 27: 771, 2006.

  • 10. 

    Tone A, Nguyen S & Devemy F et al.: Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care 38: 302, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11. 

    Jeffcoate WJ: Osteomyelitis of the foot: non-surgical management, SPECT/CT scanning and minimising the duration of antibiotic use. Diabetologia 60: 2337, 2017.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12. 

    Valabhji J, Oliver N & Samarasinghe D et al.: Conservative management of diabetic forefoot ulceration complicated by underlying osteomyelitis: the benefits of magnetic resonance imaging. Diabet Med 26: 1127, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13. 

    Lavery LA, Peters EJ & Williams JR et al.; International Working Group on the Diabetic Foot. Reevaluating the way we classify the diabetic foot: restructuring the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care 31: 154, 2008.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. 

    Peters EJ, Armstrong DG & Lavery LA: Risk factors for recurrent diabetic foot ulcers: site matters. Diabetes Care 30: 2077, 2007.

  • 15. 

    Peters EJ & Lavery LA; International Working Group on the Diabetic Foot. Effectiveness of the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care 24: 1442, 2001.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. 

    Ndip A, Lavery LA & Boulton AJ: Diabetic foot disease in people with advanced nephropathy and those on renal dialysis. Curr Diab Rep 10: 283, 2010.

  • 17. 

    Lipsky BA, Berendt AR & Deery HG et al.; Infectious Diseases Society of America. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 39: 885, 2004.

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    Lazaro-Martinez JL, Aragon-Sanchez J & Garcia-Morales E: Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care 37: 789, 2014.

    • Crossref
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    • Search Google Scholar
    • Export Citation
  • 19. 

    Acharya S, Soliman M & Egun A et al.: Conservative management of diabetic foot osteomyelitis. Diabetes Res Clin Pract 101: e18, 2013.

  • 20. 

    Aragon-Sanchez FJ, Cabrera-Galvan JJ & Quintana-Marrero Y et al.: Outcomes of surgical treatment of diabetic foot osteomyelitis: a series of 185 patients with histopathological confirmation of bone involvement. Diabetologia 51: 1962, 2008.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21. 

    Gauland C: Managing lower-extremity osteomyelitis locally with surgical debridement and synthetic calcium sulfate antibiotic tablets. Adv Skin Wound Care 24: 515, 2011.

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    Lesens O, Desbiez F & Theis C et al.: Staphylococcus aureus–related diabetic osteomyelitis: medical or surgical management? a French and Spanish retrospective cohort. Int J Low Extrem Wounds 14: 284, 2015.

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    Zeun P, Gooday C & Nunney I et al.: Predictors of outcomes in diabetic foot osteomyelitis treated initially with conservative (nonsurgical) medical management: a retrospective study. Int J Low Extrem Wounds 15: 19, 2016.

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    Lavery LA, Fulmer J & Shebetka KA et al.; Grafix Diabetic Foot Ulcer Study Group. The efficacy and safety of Grafix(®) for the treatment of chronic diabetic foot ulcers: results of a multi-centre, controlled, randomised, blinded, clinical trial. Int Wound J 11: 554, 2014.

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    Katz IA, Harlan A & Miranda-Palma B et al.: A randomized trial of two irremovable off-loading devices in the management of plantar neuropathic diabetic foot ulcers. Diabetes Care 28: 555, 2005.

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    Lavery LA, Higgins KR & La Fontaine J et al.: Randomised clinical trial to compare total contact casts, healing sandals and a shear-reducing removable boot to heal diabetic foot ulcers. Int Wound J 12: 710, 2015.

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    Aragon-Sanchez J, Lazaro-Martinez JL & Hernandez-Herrero C et al.: Surgical treatment of limb- and life-threatening infections in the feet of patients with diabetes and at least one palpable pedal pulse: successes and lessons learnt. Int J Low Extrem Wounds 10: 207, 2011.

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Are Surrogate Markers for Diabetic Foot Osteomyelitis Remission Reliable?

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Background

We aimed to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections (DFIs).

Methods

Thirty-five patients with DFIs were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histologic analysis initially and for recurrence. Fisher exact and χ2 tests were used for dichotomous variables and Student t and Mann-Whitney U tests for continuous variables (α = .05).

Results

Twenty-four patients were diagnosed as having osteomyelitis and 11 as having soft-tissue infections. Four patients (16.7%) with osteomyelitis had reinfection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed as having osteomyelitis versus soft-tissue infections. There were no differences in osteomyelitis reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for DFIs at the same site (16.7% versus 36.4%; P = .20), amputation at the same site after discharge (12.5% versus 36.4%; P = .10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate of 8.3% to 20.8%.

Conclusions

Most osteomyelitis markers were similar to markers in soft-tissue infection. Commonly reported surrogate markers were not shown to be specific to identify patients who failed osteomyelitis treatment compared with patients with soft-tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

Background

We aimed to evaluate surrogate markers commonly used in the literature for diabetic foot osteomyelitis remission after initial treatment for diabetic foot infections (DFIs).

Methods

Thirty-five patients with DFIs were prospectively enrolled and followed for 12 months. Osteomyelitis was determined from bone culture and histologic analysis initially and for recurrence. Fisher exact and χ2 tests were used for dichotomous variables and Student t and Mann-Whitney U tests for continuous variables (α = .05).

Results

Twenty-four patients were diagnosed as having osteomyelitis and 11 as having soft-tissue infections. Four patients (16.7%) with osteomyelitis had reinfection based on bone biopsy. The success of osteomyelitis treatment varied based on the surrogate marker used to define remission: osteomyelitis infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), amputation (12.5%). There was no difference in outcomes among patients who were initially diagnosed as having osteomyelitis versus soft-tissue infections. There were no differences in osteomyelitis reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for DFIs at the same site (16.7% versus 36.4%; P = .20), amputation at the same site after discharge (12.5% versus 36.4%; P = .10). Osteomyelitis at the index site based on bone biopsy indicated that failed therapy was 16.7%. Indirect markers demonstrated a failure rate of 8.3% to 20.8%.

Conclusions

Most osteomyelitis markers were similar to markers in soft-tissue infection. Commonly reported surrogate markers were not shown to be specific to identify patients who failed osteomyelitis treatment compared with patients with soft-tissue infections. Given this, these surrogate markers are not reliable for use in practice to identify osteomyelitis treatment failure.

The diagnostic gold standard of diabetic foot osteomyelitis (OM) is defined by the Infectious Diseases Society of America and the International Working Group on the Diabetic Foot as having positive microbiological culture and histopathologic findings.1,2 This is accepted for diagnosis but does not hold true in current practice for monitoring and remission of OM. Ideally, the criteria to define OM remission should be based on a direct measure of infection from bone culture and histologic testing. Unfortunately, there are no studies that use percutaneous bone culture to prove remission of OM. An alternative would be to evaluate repeated magnetic resonance imaging or leukocyte-labeled single-photon emission computed tomography, which measures bone infection/inflammation and has good diagnostic parameters to diagnose OM. This is also an uncommon practice. One randomized controlled trial and two retrospective cohort studies use advanced imaging to evaluate OM remission.3-5

Most of the current literature defines successful treatment of OM with indirect, surrogate markers for remission, including wound healing, recurrent ulcerations, amputation, and recurrent infection.6-15 Several of these surrogate markers are not specifically associated with the remission of bone infection. There is no evidence that OM is directly associated with reulceration or poor wound healing. Other surrogate markers for OM remission, such as reinfection or amputation, are common in patients with both soft-tissue and bone infections. At best, these variables have a weak association with OM treatment failure. Because most of the OM literature has relied on surrogate markers for OM remission, most of the literature may be unreliable. The purpose of this study was to compare outcomes using different definitions of OM remission.

Methods

Thirty-five patients were prospectively enrolled from July 1, 2015, to October 31, 2015, who met the criteria of 21 years or older and a moderate to severe diabetic foot skin and soft-tissue infection (DFI) based on the Infectious Diseases Society of America classification with suspicion of underlying OM.10 This study was approved by the University of Texas Southwestern Medical Center (Dallas, Texas) institutional review board before commencement. The suspicion of OM was based on initial clinical presentation, probe to bone, and radiographic and advanced imaging findings (radiography, magnetic resonance imaging). Exclusion criteria included patients with other infectious diseases, previously diagnosed OM, immunosuppressive therapies, organ or hematologic malignancy, and end-stage renal disease requiring dialysis. Eleven patients had skin and soft-tissue infections and 24 patients had OM.

Patients received standard of care medical and surgical treatments for their infections. At baseline, demographic features, medical and surgical histories, and neurologic, vascular, and wound characteristics were documented. The vascular examination included ankle-brachial index (Koven Technology Inc, St. Louis, Missouri) and skin perfusion pressure measurements and pulse volume recordings using the Sensilase Pad-ID system (Väsamed, Eden Prairie, Minnesota).16 The neurologic examination included evaluation with a 10-g Semmes-Weinstein monofilament and vibration threshold perception tests. All of the patients received empirical antibiotic coverage with vancomycin and piperacillin/tazobactam on admission to the emergency department, which was subsequently de-escalated to pathogen-directed therapy after conventional cultures and sensitivities were obtained. Bone samples were obtained from all of the patients by percutaneous bone biopsy or intraoperative surgical cultures and sent to the hospital's microbiology laboratory for conventional culture and to the pathology department for histologic examination. Osteomyelitis was defined by either positive bone culture or histologic findings. We evaluated surrogate markers commonly found in the literature: wound healing, reulceration within 12 months, readmission for a DFI within 12 months, and additional surgery or amputation within 12 months.

We compared clinical characteristics and outcomes of patients with skin and soft-tissue and bone infections using χ2 or Fisher exact tests and α = .05, and continuous variables were analyzed with the Student t test. Surrogate markers for diabetic foot OM reinfection were evaluated with χ2 or Fisher exact tests, and the continuous variable was analyzed with the Mann-Whitney U test.

Results

Twenty-four patients were diagnosed as having OM and 11 as having skin and soft-tissue infections. Patient demographic and screening characteristics are presented in Table 1. The success of OM treatment varied based on the surrogate marker used to define remission: OM infection (16.7%), failed wound healing (8.3%), reulceration (20.8%), readmission (16.7%), and amputation (12.5%). There were no differences in outcomes among patients who were diagnosed with OM versus skin and soft-tissue infections at baseline: OM reinfection (16.7% versus 45.5%; P = .07), wounds that failed to heal (8.3% versus 9.1%; P = .94), reulceration (20.8% versus 27.3%; P = .67), readmission for skin and soft-tissue infection at the index site (16.7% vs 36.4%; P = .20), or amputation at the index site after discharge (12.5% versus 36.4%; P = .10). The only difference between patients with OM and those with skin and soft-tissue infection was that there were more surgeries after discharge in those with skin and soft-tissue infections (20.8% versus 63.6%; P = .01) (Table 2).

Table 1.

Demographic and Screening Characteristics of the 35 Study Participants

Table 1.
Table 2.

Interventions and Surrogate Markers for Osteomyelitis Treatment Success

Table 2.

Discussion

The only direct measure for a diagnosis of OM is a bone biopsy sample sent for culture and histopathologic testing. This is recognized as the gold standard.17 In the present study, 16.7% of patients were found to have recurrence of OM by direct evaluation with biopsy. In contrast, most of the medical literature does not use biopsy. Instead, surrogate markers are usually used to determine recurrence of OM. This is the first study to compare the results of biopsy-proven OM and common surrogate markers for treatment success. These results indicate that indirect, surrogate markers demonstrated considerable variability compared with biopsy-confirmed recurrence, with a range of 8.3% to 20.8%. There were no differences in healing, reinfection, readmission, or amputation in patients with OM and those with skin and soft-tissue infections (Table 1). Surrogate markers demonstrate a weak relationship to OM because they have similar outcomes in patients who had a skin and soft-tissue infection.

We evaluated surrogate markers commonly found in the literature: wound healing, reulceration within 12 months, readmission for a DFI within 12 months, and additional surgery or amputation within 12 months (Table 2). If a surrogate marker is used to measure treatment failure, it should provide results that are similar to the gold standard and directly related to the disease process being monitored. This was not the case with the surrogate markers measured in this study. The common surrogate markers share several limitations in the rationale to use them. Usually there are multiple factors related to wound healing, ulcer recurrence, readmission, and surgery or amputation; OM is not the only factor related to these outcomes, and often there is only a remote association or no association with OM. In addition, most of the outcomes are affected by the quality of medical care and the wound care that patients receive, and these are not related to the presence or treatment of OM.

A common surrogate used for OM recidivism is failure to heal the wound.18-23 This is an interesting surrogate marker because wound healing has not been shown to have an association with OM treatment failure. Wound healing is poor in people with no history of infection, previous skin and soft-tissue infection, and previous OM. For example, there are low rates of diabetic foot ulcer healing in the standard of care arms of well-controlled randomized clinical trials in patients with no history of bone infection and no history of skin and soft-tissue infection that range from 18% to 32%.24-26 Wound healing is a multifactorial process, and factors such as nutrition, perfusion, glucose control, debridement, and off-loading have been associated with healing. If healing can be affected by treatment modalities, it should not be reasonable to use healing as a marker for OM treatment remission. For example, several studies have reported significant differences in the rate of healing based on the off-loading technique. A higher proportion of diabetic foot ulcers heal when treated with a total-contact cast (80%–90%) compared with removable cast boots (52%–65%) or healing sandals (45%–58%).27-29 Wounds that fail to heal could be misclassified as failed treatment for OM when the underlying cause of the failure is due to inferior wound care treatments.30,31

Another indirect marker used to define OM treatment failure is reulceration.10,18 There is no direct association of reulceration and OM or failed OM treatment that we have been able to identify. As with most of the surrogate measures, reulceration is a multifactorial process. After an ulcer or amputation heals, the risk of reulceration is very high.13,14 Patients who do not receive prevention services such as therapeutic shoes and insoles, education, and regular foot care have a very high rate of reulceration (58%–83%).32-34 The reulceration rate is cut in half when prevention is provided. As in the previous example, many patients could be misclassified as having recurrent OM or failed therapy because they did not have proper prevention services for reulceration. However, even when good prevention services are available, reulceration is very common in people with no history of infection.

Reinfection of the foot (often resulting in readmission to the hospital) is a common surrogate marker for recurrence of OM or for failed therapy.7,18,35-37 However, it is very difficult to distinguish between patients who failed initial OM treatment and patients who had successful resolution of OM and then developed a new OM or skin and soft-tissue infection at the index site. Readmission occurs in 30% to 50% of patients after they are discharged from the hospital for a foot infection.38,39 And although reinfection has been reported to be higher in people with osteomyelitis, reinfection is not unique to people with osteomyelitis. Even when good prevention care is provided, the risk of reulceration and reinfection is very high. As demonstrated by the present pilot study, patients with soft-tissue infections developed osteomyelitis 45.5% of the time during a 1-year evaluation period.

The final surrogate marker evaluated in this study was the need for additional surgery or amputation.18,37,40-42 Surgery and amputation are common in patients with soft-tissue and bone infections. Surgery or amputation may not be related to residual OM in any way. One of the consequences of amputation is the development of deformities such as hammertoes and dislocated joints to compensate for changes in the biomechanics of the foot after amputation.43,44 Surgery or amputation can be done to correct deformity that is unrelated to previous bone infection.45 Similar to most of the surrogate variables, surgery and amputation are common in patients with OM, but they also are common in people with a history of skin and soft-tissue infections and people with no previous infection. Most importantly, there is no cause-and-effect relationship that is uniquely related to the surgery/amputation and failure to treat the bone infection. In the present study, surgery was more common in people with a previous skin and soft-tissue infection.

Conclusions

In this study, the surrogate markers had similar outcomes in patients with OM and those with skin and soft-tissue infections. Developing OM at an index site of previous infection was significantly more common in this small cohort of patients with a previous skin and soft-tissue infection. Reulceration, readmission, and amputation were very similar in patients with a history of OM and those with skin and soft-tissue infections (Table 2). The need for additional surgery was greater in patients with a soft-tissue infection at baseline. This finding reinforces the concept that OM remission is not directly related to these surrogate measurements. The rationale to use surrogate markers to define OM treatment failure is very weak, suggesting that most of the OM results from clinical studies are not reliable.

Financial Disclosure: This study was funded by National Institutes of Health grant 3 U24 DK076169-08S4. Dr. Oz was supported by American Diabetes Association grant 1-17-ICTS-056.

References

  • 1. 

    Lipsky BA, Berendt AR & Cornia PB et al.; Infectious Diseases Society of America: 2012 Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infections. Clin Infect Dis 54: e132, 2012.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 2. 

    Lipsky BA, Aragon-Sanchez J & Diggle M et al.; International Working Group on the Diabetic Foot: IWGDF guidance on the diagnosis and management of foot infections in persons with diabetes. Diabetes Metab Res Rev 32 (suppl 1): 45, 2016.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 3. 

    Vouillarmet J, Moret M & Morelec I et al.: Application of white blood cell SPECT/CT to predict remission after a 6 or 12 week course of antibiotic treatment for diabetic foot osteomyelitis. Diabetologia 60: 2486, 2017.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 4. 

    Lazaga F, Van Asten SA & Nichols A et al.: Hybrid imaging with 99mTc-WBC SPECT/CT to monitor the effect of therapy in diabetic foot osteomyelitis. Int Wound J 13: 1158, 2016.

  • 5. 

    Vouillarmet J, Morelec I & Thivolet C: Assessing diabetic foot osteomyelitis remission with white blood cell SPECT/CT imaging. Diabet Med 31: 1093, 2014.

  • 6. 

    Richard JL, Lavigne JP & Got I et al.: Management of patients hospitalized for diabetic foot infection: results of the French OPIDIA study. Diabetes Metab 37: 208, 2011.

  • 7. 

    Senneville E, Lombart A & Beltrand E et al.: Outcome of diabetic foot osteomyelitis treated nonsurgically: a retrospective cohort study. Diabetes Care 31: 637, 2008.

  • 8. 

    Senneville E, Yazdanpanah Y & Cazaubiel M et al.: Rifampicin-ofloxacin oral regimen for the treatment of mild to moderate diabetic foot osteomyelitis. J Antimicrob Chemother 48: 927, 2001.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 9. 

    Embil JM, Rose G & Trepman E et al.: Oral antimicrobial therapy for diabetic foot osteomyelitis. Foot Ankle Int 27: 771, 2006.

  • 10. 

    Tone A, Nguyen S & Devemy F et al.: Six-week versus twelve-week antibiotic therapy for nonsurgically treated diabetic foot osteomyelitis: a multicenter open-label controlled randomized study. Diabetes Care 38: 302, 2015.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 11. 

    Jeffcoate WJ: Osteomyelitis of the foot: non-surgical management, SPECT/CT scanning and minimising the duration of antibiotic use. Diabetologia 60: 2337, 2017.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 12. 

    Valabhji J, Oliver N & Samarasinghe D et al.: Conservative management of diabetic forefoot ulceration complicated by underlying osteomyelitis: the benefits of magnetic resonance imaging. Diabet Med 26: 1127, 2009.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 13. 

    Lavery LA, Peters EJ & Williams JR et al.; International Working Group on the Diabetic Foot. Reevaluating the way we classify the diabetic foot: restructuring the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care 31: 154, 2008.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 14. 

    Peters EJ, Armstrong DG & Lavery LA: Risk factors for recurrent diabetic foot ulcers: site matters. Diabetes Care 30: 2077, 2007.

  • 15. 

    Peters EJ & Lavery LA; International Working Group on the Diabetic Foot. Effectiveness of the diabetic foot risk classification system of the International Working Group on the Diabetic Foot. Diabetes Care 24: 1442, 2001.

    • Crossref
    • Search Google Scholar
    • Export Citation
  • 16. 

    Ndip A, Lavery LA & Boulton AJ: Diabetic foot disease in people with advanced nephropathy and those on renal dialysis. Curr Diab Rep 10: 283, 2010.

  • 17. 

    Lipsky BA, Berendt AR & Deery HG et al.; Infectious Diseases Society of America. Diagnosis and treatment of diabetic foot infections. Clin Infect Dis 39: 885, 2004.

  • 18. 

    Lazaro-Martinez JL, Aragon-Sanchez J & Garcia-Morales E: Antibiotics versus conservative surgery for treating diabetic foot osteomyelitis: a randomized comparative trial. Diabetes Care 37: 789, 2014.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 19. 

    Acharya S, Soliman M & Egun A et al.: Conservative management of diabetic foot osteomyelitis. Diabetes Res Clin Pract 101: e18, 2013.

  • 20. 

    Aragon-Sanchez FJ, Cabrera-Galvan JJ & Quintana-Marrero Y et al.: Outcomes of surgical treatment of diabetic foot osteomyelitis: a series of 185 patients with histopathological confirmation of bone involvement. Diabetologia 51: 1962, 2008.

    • Crossref
    • PubMed
    • Search Google Scholar
    • Export Citation
  • 21. 

    Gauland C: Managing lower-extremity osteomyelitis locally with surgical debridement and synthetic calcium sulfate antibiotic tablets. Adv Skin Wound Care 24: 515, 2011.

    • Crossref
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Department of Surgery, University of Cincinnati College of Medicine, Cincinnati, OH.

Limb Preservation and Wound Research Academic Unit, Liverpool Hospital, Liverpool, Australia.

Department of Radiology, University of Texas Southwestern Medical Center, Dallas, TX.

Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX.

Sanford Orthopedics and Sports Medicine, Sanford Health, Fargo, ND.

Department of Plastic Surgery, University of Texas Southwestern Medical Center, Dallas, TX.

Corresponding author: Peter A. Crisologo, DPM, Department of Surgery, University of Cincinnati College of Medicine, 231 Albert Sabin Way, ML 0513, Cincinnati, OH 45267. (E-mail: crisolpa@ucmail.uc.edu)

Conflict of Interest: None reported.