Diabetes-related foot infections (DFIs) are one of the leading causes of hospitalization in people with diabetes.1 Outcomes with DFIs can range from successful treatment with wound care or antibiotics to lower extremity amputation. Those who suffer a severe amputation as a result of a DFI have a 5-year mortality rate of about 31%, which is similar to people with cancer.2 Therefore, prevention of DFIs with glycemic management, proper foot hygiene, and foot exams is an essential aspect of diabetes care and education. Unfortunately, even with implementation of evidence-based preventive recommendations, people with diabetes have a 34% chance of experiencing a DFI in their lifetime.3
The high risk of developing foot ulcers and infections for people with diabetes is multifactorial. Patients with diabetes-related peripheral neuropathy can unknowingly injure themselves due to loss of protective sensation.4 Diabetes also impairs the immune system. Insulin helps regulate glycolysis and aerobic metabolism, which are necessary for T-cell proliferation and cytokine production; thus, insufficient insulin can predispose the body to infection. High levels of glucose in the bloodstream can also provide an energy source to microbes at the infection site.5 Characteristics of the ulcer that may predispose the wound to infection include depth, duration, recurrence, and trauma.6 All providers caring for people with diabetes need to understand how to appropriately identify, assess, and treat DFIs because of the frequency and risk of complications. The purpose of the article is to review new recommendations from the International Working Group on the Diabetic Foot (IWGDF) and the Infectious Disease Society of America (IDSA) on the management of DFIs.
All patients with diabetes should receive education and practice healthy foot hygiene. This includes checking feet daily for sores, washing both feet every day, trimming toenails straight across to avoid sharp edges, wearing socks with shoes that fit well, having calluses professionally evaluated, and having feet checked regularly by a health care provider.7 In addition to proper education, providers should perform a risk assessment for diabetes-related foot complications at each visit to determine the frequency of foot exams. Indications that a person with diabetes may be at higher risk of developing a DFI include burning or numbness in the feet, change in color and/or temperature of the foot, dry or cracked skin, thick yellow toenails, loss of hair on the lower leg, fungal infection or “athlete’s foot,” and presence of ingrown toenails or sores. The presence of these additional complications may indicate the need for more frequent foot assessments.8
The American Diabetes Association recommends annual comprehensive foot exams consisting of dermatological, musculoskeletal, neurological, and vascular assessments. Importantly, comprehensive exams should not be confused with visual inspections. Patients at higher risk for ulcers should be assessed more frequently (Table 1).4 The dermatological and musculoskeletal assessments are visual assessments examining the integrity of the skin and assessing for the presence of foot deformities, such as bunions, hammertoes, or Charcot joints. The neurological assessment measures protective sensation using a 10-gram monofilament test in combination with at least 1 other neurological assessment, including temperature perception, pinprick sensation, ankle reflexes, or vibratory perception. The vascular assessment is used to examine blood perfusion. There are several different potential indicators of decreased perfusion, including skin discoloration or cyanosis, absent dorsalis pedis pulse, prolonged venous filling or capillary refill time, hair loss on the lower leg, or if the lower leg is cold to the touch. An ankle-brachial index (ABI) may also be useful in the diagnosis of vascular disease in these patients, but care should be taken in the interpretation of the ABI in people with diabetes due to noncompressible arterial disease or vascular stiffening due to calcification.4
Foot infections associated with diabetes are classified into 4 categories based on the IWGDF/IDSA guidelines. Ulcers with no signs or symptoms of an infection are clinically uninfected. Mild infections include local signs of infection and less than 2 cm of erythema around the ulcer, whereas moderate infections have at least 2 cm of erythema around the ulcer. Severe infections penetrate to subcutaneous tissue and may include systemic signs and symptoms of infection, such as fever, chills, hypotension, confusion, and volume depletion. Other signs of a more severe infection include extensive or rapidly progressing erythema, local discoloration, necrosis, gangrene, or the presence of complicating factors, such as acute kidney injury, presence of a foreign body, puncture wound, deep abscess, arterial or venous insufficiency, lymphedema, and immunosuppressive illness or treatment.6
Osteomyelitis complicating a DFI should be suspected when an infection is present for several weeks, extends deep and wide, is located over bony prominences, bone is visible, or is associated with an erythematous or swollen toe. Imaging with an X-ray or MRI in addition to laboratory findings and in certain cases bone culture can confirm diagnosis.6
If the clinical diagnosis or severity of a DFI is uncertain, additional laboratory tests may be useful. The presence of leukocytosis, highly elevated C-reactive protein or erythrocyte sedimentation rate, severe or worsening hyperglycemia, acidosis, and new or worsening electrolyte abnormalities are indicative of a more severe infection. Cultures are also a useful diagnostic tool that provides information on the causative pathogen(s) and their antibiotic susceptibility. Deep tissue samples are preferred to superficial swabs and should be collected after cleansing and debridement to avoid contamination with common pathogens found on the skin, such as Staphylococcus epidermidis.9 Cultures are not necessary for everyone with a DFI, specifically, in patients who have a nonsevere DFI, no recent antibiotic use, and no additional risk factors for antibiotic-resistant pathogens.6
It is important to remember that not all foot ulcers are infected and require antibiotic therapy. If an ulcer does not have at least local signs of infection, then managing with wound care alone is appropriate. If an infection is suspected, systemic antibiotic treatment is necessary. When considering antimicrobial therapy, the antibiotic selected should have the narrowest spectrum of activity to treat the most likely organisms and be administered for the shortest duration to minimize adverse effects and antimicrobial resistance.6
Choice of initial antimicrobial therapy and route of administration are also based on the severity of the infection and complicating features (Table 2). Empiric antimicrobial therapy, or treatment without culture data, may be used in cases of a mild infection and no complicating features. Treatment is based on the most common pathogens, which include gram-positive cocci (eg Staphylococcus aureus). Moderate to severe infections require broader empiric coverage initially (Table 2).6 Mild and some moderate infections can be treated with oral antibiotics, whereas severe infections should be initially treated with intravenous antibiotics. In addition to the severity of the infection, careful assessment for complicating factors should occur prior to starting treatment.
Certain complicating factors require specific antimicrobial coverage. An antibiotic with pseudomonas activity is indicated for moderate to severe infections when the following complicating patient factors are present: (1) the surrounding skin of the ulcer is breaking down or (2) in patients originating from warmer climates. Warmer weather increases skin susceptibility to infections and promotes bacterial growth, particularly for pseudomonas. The presence of an ischemic limb, necrosis, or gas-forming abscess is an indication for anaerobic bacteria coverage. Empiric coverage for methicillin-resistant Staphylococcus aureus is recommended for recent hospitalization, longterm care facility residents and prisoners, or people who participate in contact sports. If the patient has a history of infections with resistant gram-negative rods (eg, Klebsiella pneumoniae or Pseudomonas aeruginosa), then coverage should be added for extended-spectrum beta-lactamases. All empiric regimens should be de-escalated, or changed to agents with more narrow activity based on culture results.6
Moderate to severe infections tend to involve additional complicating factors and merit consideration for hospitalization. In cases where additional diagnostic testing is needed, the patient failed outpatient management, intravenous therapy is required, surgery is indicated, or the wound requires more intensive care, hospitalization is recommended due the complexity of care required. The newest guidance from IWGDF/IDSA emphasizes early surgical intervention. Delaying surgical intervention when indicated can result in more invasive procedures.
Urgent surgical intervention should be obtained in cases of severe infection or moderate infection complicated by gangrene, necrosis, deep abscess, compartment syndrome, or severe lower limb ischemia.6
The duration of therapy depends on the severity of the infection, the presence of peripheral arterial disease, and the presence of osteomyelitis with or without bone resection or amputation. In uncomplicated DFIs, the recommended duration of therapy is 1 to 2 weeks. A 7-day course of treatment is preferred, but extended duration up to 14 days may be required if the infection persists. With extensive infections or severe comorbid peripheral arterial disease, the recommended duration of therapy is 3 to 4 weeks. In patients with osteomyelitis and a positive bone margin culture (ie, infection is present) postamputation, the recommended duration of therapy is 3 weeks.6 If clear margins are achieved postamputation, antibiotics should be continued for a maximum of 2 to 5 days.10 Lastly, in patients with osteomyelitis that did not undergo bone resection or amputation, the recommended duration of therapy is 6 weeks.6
Ultimately, the management of DFIs requires interprofessional care. A podiatrist referral is recommended for those with previous ulceration or high risk for ulceration (Table 1) and may act as a facilitator with the diabetes care team.4 For more severe infections managed in the hospital, infectious disease and surgical specialists should be involved in the patient’s care. When peripheral artery disease and diabetes are present as comorbid conditions, a vascular specialist should also be consulted. Consistent with needing a team approach, the IWGDF/IDSA guidelines emphasize the importance of team members able to assist with wound care, off-loading (proper footwear), revascularization (as needed), and glycemic control. Failure to address these factors in addition to the infection will decrease the likelihood of treatment success.6 Therefore, the diabetes care and education specialist must stay up to date with best practice as a clinician who is highly likely to identify, assess, and manage an initial foot ulcer or infection.
The management of DFIs is complex and resource-intensive. Prevention of foot ulcers and infections remains the best strategy for optimizing patient outcomes. New recommendations from IWGDF/IDSA emphasize proper assessment, antibiotic selection, and treatment duration for DFIs. Incorporation of these new recommendations into practice is essential for the diabetes care team to provide holistic and comprehensive care.
Zachary A. Powers, PharmD; Anne M. Masich, PharmD, BCPS; Evan M. Sisson, PharmD, MSHA, BCACP, CDCES, FADCES; and John D. Bucheit, PharmD, CDCES, BCACP, FADCES, are with Virginia Commonwealth University School of Pharmacy in Richmond, VA.
The authors declare having no professional or financial association or interest in an entity, product, or service related to the content or development of this article.
The authors declare having received no specific grant from a funding agency in the public, commercial, or not-for-profit sectors related to the content or development of this article.
Anne M. Masich https://orcid.org/0000-0003-0728-001X
Evan M. Sisson https://orcid.org/0000-0003-3961-853X
John D. Bucheit https://orcid.org/0000-0003-3396-2612
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Rossel A, Lebowitz D, Gariani K, et al. Stopping antibiotics after surgical amputation in diabetic foot and ankle infections—a daily practice cohort. Endocrinol Diabetes Metab. 2019;2(2):e00059. doi:10.1002/edm2.59
