What is the management of a diabetic foot ulcer with infection?

From the Guidelines

Management of diabetic foot ulcers with infection requires prompt, comprehensive treatment to prevent complications like amputation, and the most recent guidelines from 2024 recommend a systematic, evidence-based approach to managing these infections, including proper diagnosis, antimicrobial therapy, and wound care 1.

Key Components of Management

• Initial management should include wound debridement to remove necrotic tissue, followed by appropriate wound dressing with materials like hydrogels or alginate dressings depending on wound characteristics.
• Infection should be treated with empiric antibiotic therapy while awaiting culture results, with the choice of antibiotics guided by the severity of the infection and the likely causative pathogens.
• For mild infections, oral antibiotics such as amoxicillin-clavulanate (875/125 mg twice daily), clindamycin (300-450 mg four times daily), or trimethoprim-sulfamethoxazole (one double-strength tablet twice daily) for 1-2 weeks are appropriate, as recommended by the 2016 IWGDF guidance 1.
• Moderate to severe infections require broader coverage, potentially with intravenous options like piperacillin-tazobactam (3.375 g every 6 hours) or ertapenem (1 g daily).

Additional Considerations

• Offloading pressure from the ulcer is crucial using total contact casting, removable cast walkers, or specialized footwear.
• Blood glucose control should be optimized with target HbA1c below 7%, as emphasized in the 2019 standards of medical care for type 2 diabetes in China 1.
• Vascular assessment is essential, as many diabetic patients have peripheral arterial disease requiring revascularization procedures.
• Regular wound assessment every 1-2 weeks allows for treatment adjustments, and a multidisciplinary approach to care is recommended, including infectious diseases specialists or clinical microbiologists, as noted in the 2004 guidelines from the Infectious Diseases Society of America 1.

From the FDA Drug Label

Adult diabetic patients with clinically documented complicated skin and skin structure infections ("diabetic foot infections") were enrolled in a randomized (2:1 ratio), multi-center, open-label trial comparing study medications administered IV or orally for a total of 14 to 28 days of treatment One group of patients received ZYVOX 600 mg q12h IV or orally; the other group received ampicillin/sulbactam 1. 5 to 3 g IV or amoxicillin/clavulanate 500 to 875 mg every 8 to 12 hours (q8–12h) orally. The cure rates in the clinically evaluable patients (excluding those with indeterminate and missing outcomes) were 83% (159/192) and 73% (74/101) in the linezolid- and comparator-treated patients, respectively A critical post-hoc analysis focused on 121 linezolid-treated and 60 comparator-treated patients who had a Gram-positive pathogen isolated from the site of infection or from blood, who had less evidence of underlying osteomyelitis than the overall study population, and who did not receive prohibited antimicrobials Based upon that analysis, the cure rates were 71% (86/121) in the linezolid-treated patients and 63% (38/60) in the comparator-treated patients.

The management of diabetic foot ulcer with infection can be treated with linezolid (ZYVOX), with a cure rate of 83% in clinically evaluable patients, and 71% in patients with a Gram-positive pathogen isolated from the site of infection or from blood, as shown in studies 2 and 2. The treatment should be administered IV or orally for a total of 14 to 28 days. It is essential to note that linezolid is not indicated for the treatment of Gram-negative infections, and specific Gram-negative therapy should be initiated immediately if a concomitant Gram-negative pathogen is documented or suspected, as stated in the label 2.

From the Research

Management of Diabetic Foot Ulcer with Infection

• Diabetic foot ulcers with infection are a serious complication in patients with diabetes mellitus, often requiring empiric antibiotic treatment 3, 4.
• The choice of antimicrobial agent for empiric treatment of moderate to severe diabetic foot infections has not been clearly established, but piperacillin/tazobactam and ampicillin/sulbactam have been shown to be effective options 3.
• Aerobic gram-positive cocci are the most common pathogens in diabetic foot infections, but gram-negative bacilli and anaerobes may also be present, especially in chronic or previously treated wounds 4.
• Initial antibiotic therapy may need to be broad-spectrum, but definitive therapy can often be more targeted based on culture and sensitivity results 4.
• The duration of treatment can range from 1-2 weeks for mild soft tissue infections to more than 6 weeks for osteomyelitis 4.
• Empirical antibiotic therapy may increase hospitalization rates, and culture-guided antibiotics may be a better approach to decrease hospitalizations 5.
• Piperacillin/tazobactam has been shown to be effective as monotherapy in diabetic foot infection, with an adequate clinical response and a level of side effects equivalent to other broad-spectrum antibiotics 6.
• In a prospective, randomized clinical trial, piperacillin/tazobactam was compared to imipenem/cilastatin for severe diabetic foot infections, and although the results did not reach statistical significance, piperacillin/tazobactam produced a better clinical response rate 7.

Antibiotic Treatment Options

• Piperacillin/tazobactam: effective against Pseudomonas aeruginosa and other gram-negative pathogens, with a bacteriologic success rate of 85.7% 3.
• Ampicillin/sulbactam: effective against aerobic gram-positive cocci and some gram-negative pathogens, but may not cover Pseudomonas aeruginosa 3.
• Imipenem/cilastatin: effective against a broad range of pathogens, including gram-negative bacilli and anaerobes, but may have a higher risk of side effects 7.

Treatment Considerations

• Surgical intervention may be required for undrained pus, wound debridement, or revascularization 4.
• Treatment duration and choice of antibiotic agent should be based on the severity of the infection, culture results, and patient response 4.
• Non-antimicrobial adjunct therapies may be helpful in some cases, such as wound care and off-loading 4.