By Conni Koury

The International Working Group on the Diabetic Foot (IWGDF) together with the Infectious Diseases Society of America (IDSA) updated previous guidance for the diagnosis and management of diabetic foot infections (DFIs) (Clin Infect Dis 2023 Oct 2; ciad527 doi: https://doi.org/10.1093/cid/ciad527).

The 2023 edition of the DFI guidelines is the first to combine the IWGDF and IDSA recommendations in a collaborative document, said lead author Éric Senneville, MD, PhD, a specialist in infectious diseases at the Gustave Dron Hospital, in Tourcoing, France.

Along with the increasing prevalence of diabetes—an estimated 537 million adults were living with diabetes in 2021—comes higher numbers of DFIs. These serious complications carry substantial morbidities, are the most frequent diabetes-related complications requiring hospitalization and are the No. 1 reason for lower extremity amputation (J Foot Ankle Surg 2014;53[6]:716-719).

Current data suggest that outcomes are suboptimal. One large prospective study found that at one year, fewer than half of patients presenting with infected diabetes-related foot ulcers were healed. Fifteen percent of these patients died, and 17% required amputation (Diabet Med 2018;35[1]:78-88).

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Writing in Clinical Infectious Diseases, the authors said these recommendations are based on updates from two 2019 systematic reviews and 62 new studies (149 studies overall were considered). The group evaluated emerging evidence specifically to include direct and patient-centered outcomes in what they said was “improved methodology applying Grading of Recommendations Assessment, Development and Evaluation principles.”

The most significant revisions pertain to the length of antibiotic therapy in patients with severe or moderate soft tissue foot infections, endorsement of bedside percutaneous bone biopsy when there is suspected diabetes-related osteomyelitis of the foot (DFO), and a change to the definition of remission as it relates to post-treatment follow-up, according to Dr. Senneville.

The integration of new evidence-based practices concerning the use of advanced wound care modalities also stands as a notable change, according to David G. Armstrong, DPM, a professor of surgery with tenure at the University of Southern California, in Los Angeles, and the founder and co-director of the Southwestern Academic Limb Salvage Alliance. “These advancements reflect the ongoing commitment of the community to integrate scientific discoveries into practical guidelines, aiming to reduce the incidence of lower limb complications and amputations,” Dr. Armstrong said. “With some 300 or 400 new studies reviewed, I think it signals an important incremental change in how we will be treating these patients in the future. With better quality data comes better decision making for us.”

It Takes a Village

The guideline authors emphasized that managing DFIs requires a multidisciplinary team, “with careful attention to properly diagnose the condition, obtain appropriate specimens for culture, thoughtfully select antimicrobial therapy, quickly determine when surgical interventions are required, and provide any needed additional wound and overall patient care.” Simply put, evidence-based approaches can improve outcomes.

Antimicrobial stewardship was a central consideration in developing the guidelines. Dr. Senneville said the IWGDF/IDSA document contributes to those efforts by providing strict recommendations for wound sampling, avoiding the misuse of broad-spectrum antibiotic regimens and shortening patients’ exposure to antibiotics.

“We propose reducing the duration of antibiotic therapy to 10 days following surgical debridement in patients with severe or moderate soft tissue infections,” Dr. Senneville said. “In addition, new data establishing the safety of bedside percutaneous bone biopsy in those with suspected DFO has led us to support this practice.” He added that the group also backs reducing the time line for establishing remission after treatment from 12 to six months.

The guidelines contribute to antimicrobial stewardship in several important ways, according to Jason C. Gallagher, PharmD, a clinical professor and clinical specialist, infectious diseases, at Temple University, in Philadelphia. As with the previous guidelines, they reinforce the idea that uninfected ulcers should not be treated with antibiotics.

Furthermore, Pseudomonas aeruginosa is not a primary DFI-involved pathogen in most parts of the world, Dr. Gallagher said, so antibiotics active against this organism are not necessary in most cases. As noted in the guidelines, mild infections are typically caused by gram-positive organisms, and when they are not, therapy can be adjusted after cultures return without harm. “This guides clinicians to treat these organisms specifically with drugs that lack activity against gram-negative bacteria, sparing collateral damage to normal flora that are best left alone,” he explained.

Controversies, Future Directions

The guidelines close with key controversies and questions for DFI management that require further investigation (see sidebar). Dr. Armstrong said there may be differing opinions regarding the specific thresholds set for surgical interventions. “The surgical management of diabetic foot conditions is a complex domain where individual patient factors significantly influence the decision-making process. Hence, there could be areas within the guidelines that might benefit from further clarification or additional evidence to support the recommendations,” he said.

9 Questions Requiring More Study

  1. How and when to determine whether an infection, including a soft tissue DFI and DFO, has resolved?
  2. What are the most useful serum biomarkers to help determine whether a DFU is infected and whether underlying osteomyelitis is present, especially when clinical and imaging assessments are inconclusive?
  3. To what extent can the currently recommended durations of antibiotic therapy be reduced for soft tissue DFIs and DFO?
  4. When and which available advanced imaging studies should clinicians order in a patient with a DFI?
  5. Does using information from a bone biopsy, including at the amputation site, improve DFO outcomes?
  6. What is the role of new antibiotics in DFI management?
  7. Is there a definition for, and practical clinical use of, the concept of chronic biofilm infection of a DFU?
  8. Does molecular (genotypic) microbiological testing for DFIs help guide antimicrobial therapy and improve outcomes?
  9. What is the potential of topical antimicrobial administration to limit the use of systemic antibiotics in DFIs?

Well-designed studies are needed to address optimal DFI classification according to infection severity, according to Dr. Senneville. Other areas for future study concern “the potential benefit of molecular techniques, and the role of positron emission tomography for DFO diagnosis as well as the impact of routine bone biopsy and rifampicin in these individuals,” he noted.

5 Areas of Focus

Developed by an international working group of clinical and scientific experts, the guidelines focus on:
  1. Diagnosing soft tissue and bone infections
  2. Collecting and identifying microbiological samples
  3. Choosing antimicrobial therapies and carrying out proper stewardship
  4. Determining when and how to approach surgical treatment
  5. Considerations for adjunctive therapies

Dr. Armstrong envisions that emerging investigations will place greater emphasis on measuring and managing the interdisciplinary approach to diabetic foot care, encompassing surgical, medical and technological interventions. “Research exploring the integration of innovative technologies such as remote monitoring and telemedicine in the continuum of care is paramount. Moreover, a deeper understanding of the microbiome and its implications on wound healing and infection control could unravel new therapeutic targets.”

Ultimately, the authors believe that following the new recommendations will help healthcare professionals provide better care for individuals with DFIs, prevent the number of foot and limb amputations, and reduce the patient and healthcare burden of diabetes-related foot disease.

25 Recommendations for Diabetic Foot Management

The guidelines make 25 recommendations that cover the diagnosis and classification of soft tissue and bone infections, the collection and processing of microbiological samples to identify causative pathogens, and antimicrobial and surgical treatments for patients with DFIs.

Diagnosis

  • Diagnose a soft tissue DFI clinically based on the presence of local or systemic signs and symptoms of inflammation.
  • Assess the severity of any DFI using the IWGDF/IDSA.
  • Consider hospitalizing all DFI patients with a severe infection or at higher risk due to relevant morbidities.
  • Assess inflammatory serum biomarkers CRP, ESR or PCT in diabetes patients with a possible infected foot ulcer but inconclusive examination.
  • Do not use foot temperature or quantitative microbial analysis for diagnosing soft tissue DFIs.
  • Consider cultures to determine the causative microorganisms, preferably by aseptically collecting a tissue specimen (via curettage or biopsy) from the wound in cases of suspected soft tissue DFIs.
  • Use conventional and not molecular microbiology techniques for the first-line identification of pathogens from soft tissue or bone samples.
  • Consider using a combination of probe-to-bone test, plain radiographs, and ESR, CRP or PCT as the initial studies to diagnose DFO.
  • Perform MRI when the diagnosis of DFO remains in doubt despite clinical, radiographic and laboratory findings.
  • Consider PET, LS or SPECT as an alternative to MRI for the diagnosis of DFO.
  • If there is a suspicion of DFO, bone samples (not soft tissue) should be obtained intraoperatively or percutaneously.
  • Do not treat clinically uninfected DFUs with systemic or local Abx when the goal is to reduce the risk for new infection or to promote ulcer healing.

Treatment

  • Use systemic Abx with proven efficacy in published randomized controlled trials at standard dosing to treat soft tissue DFIs.
  • Administer Abx for 1 to 2 wk for skin or soft tissue DFIs.
  • Consider up to 3 to 4 wk of treatment if the infection is improving but extensive and slow to resolve or if the patient has severe PAD.
  • If evidence of infection has not resolved after 4 wk of therapy, reevaluate the patient and reconsider the need for further studies or alternative treatments.
  • Select Abx based on the likely or proven causative pathogen(s) and their antibiotic susceptibilities; the clinical severity of the infection; published evidence of the efficacy of the agent for infections of the diabetes-related foot; the risk for AEs, including collateral damage to the commensal flora; the likelihood of drug interactions; and agent availability and costs.
  • Target aerobic gram-positive pathogens only (beta-hemolytic streptococci and Staphylococcus aureus including methicillin-resistant strains, if indicated) for people with a mild DFI, who have not recently received antibiotic therapy, and who reside in North America or Western Europe.
  • Do not empirically target antibiotic therapy against Pseudomonas aeruginosa in cases of DFIs in temperate climates, but use empiric treatment of P. aeruginosa if it has been isolated from cultures of the affected site within the previous few weeks, in a person with moderate or severe infection who resides in Asia or North Africa.
  • Consider up to 3 wk of Abx after minor amputation for DFO and positive bone margin culture and 6 wk for DFO without bone resection or amputation.
  • Diagnose remission of DFO based on minimum follow-up duration of 6 mo after cessation of the Abx.
  • Urgent surgical consultation should be obtained in cases of severe infection or moderate DFI complicated by extensive gangrene, necrotizing infection, signs suggesting deep abscess, compartment syndrome or severe lower limb ischemia.
  • Consider performing surgery within 24 to 48 h plus Abx for moderate and severe DFIs to remove the infected and necrotic tissue.
  • For PAD and a DFU or gangrene with infection involving any portion of the foot, obtain an urgent surgical and vascular consultation to determine the indication and timing of drainage and/or revascularization.
  • Consider performing surgical resection of infected bone combined with systemic antibiotics in patients with DFO.
  • Consider Abx without surgery in case of forefoot osteomyelitis without an immediate need for incision and drainage to control infection, without PAD and without exposed bone.

Approaches Not Endorsed

  • Suggest NOT using the adjunctive G-CSF treatment or topical antiseptics, silver preparations, honey, bacteriophage therapy, or negative pressure wound therapy.
  • Suggest NOT using topical (sponge, cream and cement) antibiotics with systemic antibiotics for treating either soft tissue DFIs or DFO.
  • Suggest NOT using hyperbaric oxygen or topical oxygen therapy as an adjunctive treatment for the sole indication of treating a DFI.

Abx, antibiotics; AEs, adverse events; CRP, C-reactive protein; DFI, diabetic foot infection; DRO, diabetes-related osteomyelitis; DFUs, diabetic foot ulcers; ESR, erythrocyte sedimentation rate; G-CSF, granulocyte colony-stimulating factor; IWGDF, International Working Group on the Diabetic Foot; IDSA, Infectious Diseases Society of America; LS, leucoyte scintigraphy; PAD, peripheral artery disease; PCT, procalcitonin; SPECT, single-photon emission computed tomography.

Clin Infect Dis 2023 Oct 2; ciad527 doi: https://doi.org/10.1093/ cid/ ciad527