Preventing and Treating Diabetic Foot Infections

US Pharm. 2024;49(4):17-20.

ABSTRACT: Diabetic foot infections (DFIs) are one of the most common complications in individuals with diabetes. DFIs involve inflammatory responses that mimic peripheral neuropathy and peripheral vascular disease, which may result in delayed diagnosis and treatment. Multiple microorganisms may be involved, and treatment often requires a multimodal approach. Clinical practice guidelines recommend an interprofessional team to manage and treat DFIs. Pharmacists can provide pharmacotherapy recommendations to healthcare providers in both inpatient and outpatient settings. Pharmacists can also provide education to patients regarding diabetes control, proper foot care and self-examination techniques, medication adherence, smoking cessation, and management of medication side effects.

Diabetes is a prevalent and complicated chronic condition, affecting about 11% of people living in the United States.¹ Because of the disease progression and complications associated with diabetes, this patient population is at risk for skin and soft tissue infections (SSTIs), which are often more complicated and difficult to treat than SSTIs in patients without diabetes. One SSTI that patients with diabetes commonly experience is a diabetic foot infection (DFI). A DFI can occur when a patient with diabetes develops a foot wound that later becomes infected. These infections may lead to serious complications, such as bone infections and limb amputations.^2,3 It is imperative that patients with DFIs receive prompt and appropriate pharmacologic therapy and surgical or medical management, if indicated.

Etiology and Epidemiology

Poor glycemic control in those with diabetes can lead to microvascular and macrovascular complications, such as peripheral neuropathy and peripheral vascular disease, which in turn can lead to a greater risk of these patients developing DFIs.³ Peripheral neuropathy, for example, reduces sensitivity to the extremities, which may cause lesions or injuries in those areas to go unnoticed. If the wounded area becomes infected, the lack of lower limb sensation may lead to patients waiting to seek treatment, potentially contributing to more complications and increased infection severity. Those with diabetes may also experience autonomic neuropathy, resulting in reduced sweat secretion and dry skin. This causes the skin to be more prone to cracking and lesions, increasing the risk of infection.^4,5 Peripheral vascular disease can reduce the mobilization of immune cells to the site of the infection, prolonging healing time and further allowing infections to proliferate.⁴

DFIs are associated with an increased burden of disease complications, including hospitalizations, amputations, and mortality. Patients with diabetes who develop a DFI have a mortality rate two-and-a-half times higher than patients with diabetes who do not have DFIs. About 40% of patients with a DFI will have a recurrent infection within 1 year, contributing to the economic burden of the illness and reducing quality of life, especially in patients who require amputation, which occurs in approximately 20% of DFIs.⁵

It is estimated that about 13% of North American patients with diabetes will experience a DFI in their lifetime, and approximately 40 million people worldwide with diabetes develop foot ulcers annually.⁶ DFIs occur most commonly in North America; however, the number of people living with diabetes in Africa and South America has increased, so the number of DFIs may subsequently increase with this trend.

There are notable sex-based trends related to the incidence of DFIs. For example, men are more likely than women to develop DFIs and require amputations. Women have demonstrated a higher likelihood of performing foot care and self-examinations than men, which is one possible explanation for this difference in incidence rates. Men are also more likely than women to experience diabetes-related complications, such as peripheral neuropathy, peripheral artery disease, and cardiovascular disease. When considering age-related trends, elderly patients are more likely to experience DFIs and comorbid vascular complications, but younger patients tend to seek medical attention when more severe infections have developed.⁷ Although elderly patients are more likely to experience DFIs and complications, younger patients are at a higher risk for experiencing recurrent DFIs. Younger patients are generally active and mobile, so there is an increased risk of reinjuring the site of a previous DFI, which may lead to the development of subsequent DFIs.^7,8

Disparities among black and Hispanic/Latino patients with diabetes are prevalent, as these demographic groups experience higher rates of both diabetes and DFIs and have statistically worse outcomes related to DFIs, such as higher rates of amputations and hospitalizations, compared with white and non-Hispanic/Latino patients. Other factors correlated with negative DFI outcomes include limited health insurance coverage, lower education levels, limited resources in socioeconomically deprived neighborhoods, and reduced access to preventive and specialty care.⁹

Clinical Presentation and Management

Appropriate treatment of a DFI requires proper classification of the infection, as the treatment changes based on the severity. According to the guidelines published by the International Working Group on the Diabetic Foot/Infectious Diseases Society of America (IWGDF/IDSA), an uninfected foot wound is typically asymptomatic in its presentation and should not be treated with antibiotics.¹⁰ However, as the infection becomes more severe, the symptoms become more systemic and require more aggressive treatment. TABLE 1 classifies DFIs based on their symptom severity.¹⁰

Selection of an empiric antibiotic regimen is based on both the severity of the DFI and the spectrum of activity against the suspected pathogens. Staphylococcus aureus and Streptococcus species are commonly implicated bacterial organisms in DFIs, so the selected regimen should provide coverage for these pathogens.¹¹ Mild infections can be treated empirically, usually outpatient, with cephalexin (or a similar first-generation cephalosporin) or amoxicillin/clavulanate. These agents provide activity against methicillin-sensitive S aureus (MSSA) and streptococci. Fluoroquinolones are an alternative option for those with a severe beta-lactam allergy. If the patient is suspected to have a methicillin-resistant S aureus (MRSA) infection, he or she can instead be prescribed doxycycline or trimethoprim/sulfamethoxazole.¹⁰ Treatment of mild DFIs includes oral antibiotics for 2 weeks. Moderate infections can be treated with oral or parenteral antibiotics, depending on infection severity. If there is further involvement of deep tissue or bone, parenteral antibiotics are indicated. Severe infections with systemic manifestations of illness require parenteral antibiotics.¹⁰

Empiric antibiotic therapy for moderate or severe infections should include gram-positive, gram-negative, and anaerobic coverage. Empiric antibiotic regimens can include ceftriaxone (or a similar third-generation cephalosporin) with metronidazole or ampicillin/sulbactam.¹⁰ If the patient has MRSA risk factors, such as a history of MRSA infection, purulence or drainage from the wound, or a severe infection that does not respond to initial empiric therapy, vancomycin or linezolid can be added. Pseudomonas aeruginosa is not often isolated from DFIs, but therapy can be escalated to an antibiotic such as piperacillin/tazobactam or cefepime if patients have compelling P aeruginosa risk factors, such as chronic decubitus ulcers or a severe infection not responding to initial empiric therapy.¹⁰ See TABLE 2 for a summary of empiric antibiotic options based on infection severity.¹⁰ Treatment of moderate-to-severe DFIs initially includes IV antibiotics, then often transitions to oral therapy for 2 to 4 weeks.^10,12

When surgery is indicated for a DFI, it should ideally be performed within 24 to 48 hours of hospital admission. According to the IWGDF/IDSA clinical practice guidelines, surgical intervention should be considered for treating patients with severe DFIs and/or when there is a risk that nonsurgical interventions will be ineffective in treating the DFI.¹⁰ Treatment of DFIs with bone or joint involvement includes IV antibiotics initially, then often transitions to oral treatment for 2 to 5 days if the wound is resected. However, therapy may last for 1 to 2 weeks if a wound debridement is performed, 3 weeks if there is a positive culture after resection, or 6 weeks if there is dead bone and/or no surgery is performed.^10,12

Osteomyelitis, a tissue infection that includes the bone, is a possible complication of DFIs. Patients who develop osteomyelitis secondary to a DFI should be reevaluated within 6 months of completing antibiotic therapy to determine remission.^2,10,12 If soft tissue injury in the setting of osteomyelitis is irreversible and attempts at revascularization are unsuccessful, amputation must be performed. Early amputation, when clinically indicated, will often prevent the necessity of major lower extremity amputations. Once a DFI progresses to an amputation, antibiotic therapy for up to 3 weeks is appropriate. The duration of therapy can vary, with 1 to 4 weeks being indicated in most DFIs, but it may be extended if the wound is large or if healing is prolonged.^10,12 Many patients who begin DFI treatment with parenteral therapy may eventually transition to oral therapy that either provides a similar spectrum of activity or is guided by cultures, as long as the patient is demonstrating clinical improvement and does not have a diagnosis of osteomyelitis.¹⁰

Preventive Care Strategies

One of the most effective ways to prevent DFIs is to implement preventive foot care measures. Effectively managing diabetes and incorporating preventive strategies can slow the onset of symptom progression and/or prevent complications related to DFIs.³ There are several strategies that patients can incorporate to help prevent DFIs, including checking their feet daily for wounds or sores, keeping their feet hydrated with lotion, clipping their toenails regularly, and wearing socks with comfortable, protective shoes. Patients should not only be encouraged to perform daily self-checks for foot care but also urged to attend annual appointments to have their feet evaluated for adequate nerve sensation and function. During these appointments, signs and symptoms of neuropathy can be addressed before worsening nerve damage occurs. One important way to prevent progression of neuropathy is to encourage patients to implement smoking cessation techniques, as smoking increases the risk for developing macrovascular and microvascular complications.³

Nonpharmacologic Management

If a patient’s foot still becomes infected despite best efforts, there are some nonpharmacologic interventions that can be helpful when combined with pharmacologic management. Hyperbaric oxygen therapy has gained popularity for treating several conditions in recent years.³ However, per the 2023 IWGDF/IDSA guideline, hyperbaric oxygen therapy is not recommended for the adjunctive treatment of DFIs due to a lack of compelling beneficial evidence.¹⁰ Honey has long been regarded as an antibacterial agent that is commonly used to help treat or prevent infections. However, although honey does demonstrate antibacterial properties, the 2023 IWGDF/IDSA guideline recommends against using topical honey for the treatment of DFIs.^10,13 Healthy lifestyle modifications, such as the daily incorporation of strategies for managing weight, diet, and exercise, can contribute to maintaining blood glucose control. Since uncontrolled blood glucose can lead to progressive nerve damage, patients should strive to maintain blood glucose control by incorporating lifestyle modifications and taking their antidiabetic medications as prescribed to potentially delay and/or prevent DFIs.^3,14,15

Role of the Pharmacist

As one of the most accessible healthcare professionals, pharmacists can play a vital role in both the prevention and management of DFIs. Pharmacists can help counsel patients picking up antidiabetic medications on the importance of daily foot checks, annual appointments, smoking cessation techniques, lifestyle modifications, and the importance of medication adherence and blood glucose monitoring. Other services, such as medication therapy management, point-of-care glucose testing, and medication synchronization, can help promote disease state and medication adherence in patients with diabetes.^15-17 Additionally, when patients being treated for DFIs fill antibiotic prescriptions, pharmacists can help ensure that the antibiotic and duration of therapy are appropriate for treating the patient’s infection. Pharmacists can offer counseling to patients to help mitigate antibiotic misuse and promote adherence, as well as to educate patients about how to manage common side effects that may occur with their medications.^10,13,15-17

Conclusion

The potentially debilitating complications resulting from DFIs highlight the importance of effectively managing glucose levels and routinely monitoring feet for new wounds and/or sores.^10,15 As medication experts, pharmacists can offer pharmacologic, nonpharmacologic, and disease state–related counseling and education to patients living with diabetes, contributing to positive health outcomes.¹⁵ Community and ambulatory care pharmacists are well positioned to communicate with healthcare providers and provide therapeutic interventions to ensure that patients are being optimally and appropriately managed for diabetes and/or DFIs. Optimal disease-state management and appropriate use of medications can contribute to improved symptoms and overall quality of life for patients.^10,15-17

REFERENCES

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