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

Abstract¹

The International Working Group on the Diabetic Foot (IWGDF) has provided evidence-based guidance for managing and preventing foot issues in individuals with diabetes since 1999. The 2019 update of their guidelines on diagnosing and managing foot infections in diabetes patients is a highlight.

These guidelines have evolved meticulously, using the Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) framework. Key clinical questions, patient-relevant outcomes, and a thorough review of available evidence were considered to create recommendations that directly impact patient care.

This update incorporated two systematic reviews from 2019, including 62 new studies out of 149 meeting inclusion criteria. When solid evidence was lacking, best practice statements were included. The guidelines evaluate the benefits and drawbacks of evidence to offer practical recommendations, enhancing the certainty of evidence using the GRADE framework.

The recommendations cover the diagnosis and classification of soft tissue and bone infections, as well as guidance on microbiological sample collection. They also address antimicrobial therapy selection, surgical intervention, and adjunctive treatments for foot infections in diabetes patients. Following these recommendations can reduce the need for foot and limb amputations, lessening the burden on both patients and the healthcare system due to diabetes-related foot issues.

Introduction

Diabetes prevalence is on the rise worldwide, with an estimated 537 million adults aged 20 to 79 affected in 2021, leading to an increased incidence of foot complications, notably infections.^2,3 Diabetes-related foot infections (DFIs) are linked to significant health challenges, necessitating frequent medical visits, daily wound care, antimicrobial treatment, surgical procedures, and high healthcare costs. Importantly, DFIs are the leading cause of diabetes-related hospitalizations and the primary trigger for lower extremity amputations.³

Patients with infected diabetes-related foot ulcers (DFUs) often experience suboptimal outcomes, with only 46% healing in one year, 15% mortality, and 17% requiring amputation.⁴

Managing DFIs requires precise diagnosis, appropriate culture specimen collection, thoughtful antimicrobial therapy selection, prompt identification of the need for surgery, and comprehensive patient care. An evidence-based approach by interdisciplinary teams, preferably with infectious disease or clinical microbiology specialists, is essential to improve outcomes and prevent complications. It’s crucial to address wound care, off-loading, vascular assessment, and metabolic control alongside infection management to reduce treatment failure.^{3 ,4}

Multiple guidelines are available to aid clinicians in managing DFIs, with the latest 2023 edition combining the expertise of IWGDF and IDSA members.

Background

In individuals with diabetes, skin and soft tissue infections in the foot typically originate from breaks in the protective skin barrier, most commonly diabetic foot ulcers (DFUs), which often involve the epidermis and part of the dermis. These complications are prevalent in individuals with peripheral neuropathy and peripheral arterial disease (PAD). Infection arises from the colonization of the wound by a complex microbiological flora. Wound colonization involves the presence of bacteria on the wound surface without invading host tissues. In contrast, wound infection results from microorganisms invading and multiplying in host tissues, causing inflammation and tissue damage.^1,5

Diabetic foot infections (DFIs) are clinically defined by inflammatory signs in a foot wound below the malleoli, which can be challenging to detect due to conditions like neuropathy or PAD. The combination of infection and PAD significantly increases the risk of poor healing and amputation, necessitating prompt evaluation of wound perfusion and potential revascularization.^3,4

Predisposing factors for foot infection include deep or long-standing wounds, traumatic origins, immunological perturbations, and chronic renal failure. Chronic hyperglycemia may also contribute to DFIs. While most DFIs start superficially, they can spread to deeper tissues, driven by the foot’s compartmental anatomy and infection-induced pressure increases.^1,2

Severe DFIs can present with systemic symptoms, indicating a potential limb- or life-threatening condition. Rapid diagnosis and appropriate treatment by an infectious disease specialist are essential. Accumulations of purulent secretions require surgical decompression and drainage within 24 hours, and osteomyelitis may necessitate limited resection. This document offers evidence-based guidelines for diagnosing and treating foot infections in diabetic patients to aid clinicians.¹

Methodology¹

^{Figure 1. An overview of the diagnosis and management of patients with Diabetes-related foot infections (DFIs) (from Lipsky et al. DMRR 2019). Perform non-invasive bedside tests for peripheral artery disease (PAD).}

The guideline development process follows the GRADE framework, which defines key clinical questions in the Population, Assessment, Comparison, Outcome (PICO) format. A multidisciplinary working group of independent experts, including three members delegated by the IDSA, was appointed by the IWGDF editorial board to update the 2019 guidelines.

Key clinical questions were refined to reflect clinical relevance, with patient-important outcomes generated and classified based on decision-making importance. Outcomes identified as “critically important” by consensus were included. The committee systematically reviewed the literature to address these questions, supported by two updated systematic reviews. Recommendations were developed to be clear, specific, and unambiguous, rated as ‘for’ or ‘against’ the intervention, with a strength rating of ‘strong’ or ‘conditional.’ Certainty of evidence, rated as ‘high,’ ‘moderate,’ ‘low,’ or ‘very low,’ was added to recommendation strength based on critical outcomes.

Summary of judgments tables and recommendations were extensively discussed in online meetings, followed by a voting procedure to grade the direction and strength of recommendations. Rationales for recommendations, including research evidence and expert opinion, were written by assessment teams. All recommendations and rationales were reviewed by international external experts, patients with lived experience, and the IWGDF Editorial Board, with feedback incorporated to produce the final guidelines.

The detailed methodology for guideline development is outlined in the publication “Standards for the development and methodology of the 2023 IWGDF guideline.”

List of Recommendations¹

• Recommendation 1:
  1. Clinically diagnose soft tissue diabetes-related infections based on local or systemic signs of inflammation. (Strong; Low evidence).
  2. Assess the severity of Diabetes-related foot infections (DFI) using the IWGDF/IDSA classification. (Strong; Low)
     
     ^{Table 1. The classification system for defining the presence and severity of foot infection in a person with diabetes.a}
     
• Recommendation 2: Consider hospitalizing diabetes patients with foot infections classified as severe or moderate with relevant health issues. (Conditional; Low)
• Recommendation 3: Use inflammatory serum biomarkers if clinical diagnosis is inconclusive in diabetes patients with foot ulcers. (Best Practice Statement)
  
  
• Recommendation 4: Avoid using foot temperature or quantitative microbial analysis for diagnosing soft tissue DFI. (Conditional; Low)
• Recommendation 5: Consider culture samples for causative microorganisms in suspected soft tissue DFI using aseptically collected tissue specimens. (Conditional; Moderate).
• Recommendation 6: Use conventional, not molecular, techniques for pathogen identification from soft tissue or bone samples in DFI patients. (Strong; Moderate).
  
  ^{Table 3. Features characteristic of diabetes-related osteomyelitis of the foot on plain X-rays.}
  
• Recommendation 7: Consider a combination of tests for diagnosing foot osteomyelitis in diabetes patients. (Conditional; Low)
• Recommendation 8: Using MRI when diagnosing diabetes-related foot osteomyelitis is uncertain despite clinical findings. (Strong; Moderate)
• Recommendation 9: Consider alternative imaging methods like PET, scintigraphy, or SPECT if MRI is unsuitable for diagnosing foot osteomyelitis. (Conditional; Low)
• Recommendation 10: Obtain bone samples for culture if osteomyelitis is suspected in diabetes patients. (Conditional; Moderate)
• Recommendation 11: Do not treat uninfected foot ulcers with antibiotics for prevention or healing. (Best Practice Statement)
• Recommendation 12
  1. Use effective antibiotic regimens for soft tissue DFI in diabetes patients, with treatment lasting 1–2 weeks. (Strong; High)
  2. Consider longer treatment if the infection is extensive or the patient has severe PAD. (Conditional; Low)
  3. Reevaluate if the infection persists after four weeks of appropriate therapy. (Strong; Low)
• Recommendation 13: Select antibiotics based on causative pathogens, clinical severity, efficacy, side effects, interactions, availability, and costs. (Best Practice Statement)
• Recommendation 14: Target specific pathogens for mild DFI in North America or Western Europe. (Best Practice Statement)
• Recommendation 15: Do not empirically target Pseudomonas aeruginosa in DFI in temperate climates, but consider it in Asia or North Africa if isolated recently. (Best Practice Statement)
• Recommendation 16: Administer antibiotic therapy for osteomyelitis with amputation for up to 3 weeks and six weeks without amputation. (Conditional; Low)
• Recommendation 17: Use a 6-month follow-up to diagnose remission of osteomyelitis. (Best Practice Statement)
• Recommendation 18: Seek surgical consultation for severe or moderate DFI with complications. (Best Practice Recommendation)
• Recommendation 19: Consider surgery combined with antibiotics within 24–48 hours for moderate and severe DFIs. (Conditional; Low)
• Recommendation 20: Consult surgical and vascular specialists for PAD and infected foot ulcers or gangrene in diabetes patients. (Best Practice Statement)
• Recommendation 21: Consider surgical resection of infected bone with systemic antibiotics for foot osteomyelitis. (Conditional; Low)
• Recommendation 22: Use antibiotics without surgery for specific cases of forefoot osteomyelitis without PAD and exposed bone. (Conditional; Low)
• Recommendation 23: Avoid treatments like G-CSF, antiseptics, silver, honey, bacteriophage, and negative-pressure wound therapy for DFIs. (Conditional; Low)
• Recommendation 24: Do not combine topical and systemic antibiotics for foot infections in diabetes patients. (Conditional; Low)
• Recommendation 25: Do not use Hyperbaric or topical oxygen therapy solely for DFI treatment. (Conditional; Low)

Treatment¹

^{Table 4. Proposals for the empirical antibiotic therapy according to clinical presentation and microbiological data (from Lipsky et al.11).a}

Most diabetic foot infections (DFIs) can be effectively treated with carefully chosen antibiotics, necessary surgical procedures, and proper management of the patient’s metabolic health and wound care. Mild infections are commonly caused by gram-positive bacteria like beta-hemolytic streptococci and S. aureus. In the case of mild infections, there is room to modify the antibiotic treatment if cultures reveal resistant or non-gram-positive cocci organisms. If the infection persists, treatment should be adjusted based on the specific bacteria identified in the cultures. For moderate or severe DFIs, refer to Table 4 for suggested empirical antibiotic therapy. Pseudomonas species are less frequently found in North America and Europe but are more prevalent in (sub)tropical regions. Given the complexity and often polymicrobial nature of DFIs, it is crucial to follow the principles of antibiotic stewardship. This involves controlling the source of infection through surgery when possible and initially using empiric antibiotics with the narrowest spectrum, shortest duration, minimal side effects, the safest route, and the least expensive option. If necessary, transition to targeted oral antibiotic therapy based on the identified pathogens.

Areas with Limited or Inconsistent Evidence

Bioactive glass compounds have been applied topically as an adjunct treatment in surgical cases of diabetic foot osteomyelitis (DFO). However, insufficient data hinders us from recommending this therapeutic approach. Current treatment guidelines do not endorse any specific antibiotic for foot osteomyelitis in diabetic patients. Nevertheless, our systematic review identified two retrospective studies suggesting that adding rifampicin to a combination antimicrobial regimen may enhance cure rates for osteomyelitis. The certainty of this evidence is low due to inconsistent outcomes. Given the potential for drug-related adverse events and the risk of drug interactions, particularly in elderly patients often taking other medications, it is advisable to gather valid data on its potential benefits before considering its routine use.

Key Controversies¹

Several aspects of diabetic foot infection (DFI) management still require further exploration. The following questions represent the areas of greatest interest:

• How and when should we determine if an infection, whether in soft tissue or osteomyelitis, has been successfully resolved?
• What are the most effective serum biomarkers for identifying infection in a diabetic foot ulcer (DFU), particularly when clinical and imaging assessments yield inconclusive results?
• To what extent can we reduce the currently recommended durations of antibiotic therapy for soft tissue and osteomyelitis in DFIs?
• When should clinicians order advanced imaging studies, and which should be used in patients with DFIs?
• Does utilizing information from a BeBoP, including at the amputation site, lead to improved outcomes in cases of diabetic foot osteomyelitis (DFO)?
• Where do various new antibiotics fit into the management of DFIs?
• Is there a well-defined concept and practical clinical application for chronic biofilm infection in DFUs?
• Can molecular (genotypic) microbiological testing for DFIs aid in guiding antimicrobial therapy and enhancing outcomes?
• What is the potential of topically administering antimicrobials to reduce the need for systemic antibiotics in DFIs?

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References

1. Éric Senneville, Zaina Albalawi, Suzanne A van Asten, Zulfiqarali G Abbas, Geneve Allison & et al., IWGDF/IDSA Guidelines on the Diagnosis and Treatment of Diabetes-related Foot Infections (IWGDF/IDSA 2023), Clinical Infectious Diseases, 2023; ciad527, https://doi.org/10.1093/cid/ciad527
2. International Diabetes Federation. IDF Diabetes Atlas. 10th ed. Belgium; 2021. https://www.diabetesatlas.org
3. Raspovic KM, Wukich DK. Self-reported quality of life and diabetic foot infections. Journal of Foot and Ankle Surgery. 2014; 53(6):716–719. https://doi.org/10.1053/j.jfas.2014.06.011.
4. Peters EJ, Childs MR, Wunderlich RP, Harkless LB, Armstrong DG, Lavery   LA. Functional status of persons with diabetes-related lower extremity amputations. Diabetes Care. 2001; 24(10):1799–1804. https://doi.org/10.2337/diacare.24.10.1799.
5. Lavery LA, Armstrong DG, Murdoch   DP, Peters   EJ, Lipsky   BA. Validation of the Infectious Diseases Society of America’s diabetic foot infection classification system. Clinical Infectious Disease. 2007; 44(4):562–565. https://doi.org/10.1086/511036

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