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Am Fam Physician. 2021;104(4):386-394

Related Letter to the Editor: Caution Before Antibiotic De-escalation Following Negative MRSA Nares Testing 

Patient information: See related handout on preventing diabetic foot infections.

This clinical content conforms to AAFP criteria for CME.

Author disclosure: No relevant financial affiliations.

Diabetes-related foot infections occur in approximately 40% of diabetes-related foot ulcers and cause significant morbidity. Clinicians should consider patient risk factors (e.g., presence of foot ulcers greater than 2 cm, uncontrolled diabetes mellitus, poor vascular perfusion, comorbid illness) when evaluating for a foot infection or osteomyelitis. Indicators of infection include erythema, induration, tenderness, warmth, and drainage. Superficial wound cultures should be avoided because of the high rate of contaminants. Deep cultures obtained through aseptic procedures (e.g., incision and drainage, debridement, bone culture) help guide treatment. Plain radiography is used for initial imaging if osteomyelitis is suspected; however, magnetic resonance imaging or computed tomography may help if radiography is inconclusive, the extent of infection is unknown, or if the infection orientation needs to be determined to help in surgical planning. Staphylococcus aureus and Streptococcus agalactiae are the most commonly isolated pathogens, although polymicrobial infections are common. Antibiotic therapy should cover commonly isolated organisms and reflect local resistance patterns, patient preference, and the severity of the foot infection. Mild and some moderate infections may be treated with oral antibiotics. Severe infections require intravenous antibiotics. Treatment duration is typically one to two weeks and is longer for slowly resolving infections or osteomyelitis. Severe or persistent infections may require surgery and specialized team-based wound care. Although widely recommended, there is little evidence on the effectiveness of primary prevention strategies. Systematic assessment, counseling, and comorbidity management are hallmarks of effective secondary prevention for diabetes-related foot infections.

Diabetes-related foot infections form in approximately 40% of foot ulcers in patients with diabetes mellitus.1 Infections can rapidly progress to cellulitis, abscess formation, osteomyelitis, and necrotizing fasciitis. In 2016, diabetes-related foot infections contributed to more than 130,000 lower-extremity amputations in the United States.2 The five-year mortality rate following amputation is approximately 50%, exceeding the mortality rate of many cancers.3


Patients with diabetes and vascular compromise, peripheral neuropathy, and impaired immune function are at high risk of developing foot infections. The risk increases with deformities (e.g., bunions, hammer toe, Charcot foot) that result in high compressive forces in certain areas of the foot.4 Peripheral neuropathy causes the loss of protective sensation for pain and temperature and increases the risk of foot trauma and ultimately foot ulceration. Approximately 50% of patients with neuropathy are asymptomatic, making recognition of a patient with an ulcer difficult.5 When the skin ulcerates, an infection can develop rapidly because of circulatory compromise and an impaired immune response. Infection can spread rapidly to surrounding tissues, initially causing cellulitis and later more severe complications such as osteomyelitis and necrotizing fasciitis.6


The most commonly isolated organisms from diabetes-related foot infections are the gram-positive bacteria Staphylococcus aureus, Staphylococcus epidermidis, Streptococcus agalactiae (i.e., group B Streptococcus), and Enterococcus species. Wounds infected by methicillin-resistant S. aureus (MRSA) occur in approximately 15% of cases and are more serious considering the virulence of MRSA and the limited number of treatment options.7 Gram-negative bacteria are common and isolated in more than one-half of samples, particularly the Enterobacteriaceae group and Pseudomonas aeruginosa.8 Anaerobes are present in about one-third of cultures. Bacteroides fragilis, Prevotella, Porphyromonas, and Clostridium species are the most common.9 Approximately 50% to 80% of infections are polymicrobial, which complicates treatment.10

Diagnostic Evaluation

Prompt diagnosis of a diabetes-related foot infection decreases the risk of morbidity and mortality. Family physicians should consider patient risk factors (e.g., presence of foot ulcers greater than 2 cm, uncontrolled diabetes, poor vascular perfusion, comorbid illness) when assessing for infection. Findings suggestive of infection include erythema, induration, tenderness, warmth, and drainage. The probe-to-bone test is an office maneuver that is 87% sensitive and 83% specific for osteomyelitis.11 A probe-to-bone test result is positive if insertion of a sterile and blunt metal instrument is met with hard or gritty resistance. An erythrocyte sedimentation rate greater than 70 mm per hour is also suggestive of osteomyelitis.4,6 Other causes of inflammation (e.g., gout, rheumatoid arthritis, trauma) should be clinically ruled out.

Although an elevated white blood cell count can indicate a more severe infection, it is not often elevated with a diabetes-related foot infection. C-reactive protein and procalcitonin correlate better to soft tissue bacterial infections than erythrocyte sedimentation rate and white blood cell count.6 Routine superficial wound cultures should be avoided because of the high rate of contaminants; however, deep tissue cultures obtained using aseptic procedures (i.e., incision and drainage, debridement, and bone culture) help guide treatment.6,12 A negative MRSA nares culture reduces the likelihood that a diabetes-related foot infection is caused by MRSA. Studies have shown correlations with negative predictive values between 73% and 90%.13,14

Plain radiography should be the initial imaging test if osteomyelitis is suspected.6,15 Osteomyelitis can take weeks to appear on radiographs; therefore, magnetic resonance imaging (MRI) or computed tomography (CT) is warranted if a concern for osteomyelitis persists with normal radiography findings. MRI helps detect soft tissue involvement and identifies the spatial orientation of infection to guide surgical planning. CT is appropriate if MRI is contraindicated.15

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