Diabetes-Related Foot Infections:​

Diagnosis and Treatment

Eric M. Matheson, MD, MS;​Scott W. Bragg, PharmD;​and Russell S. Blackwelder, MD, MDiv
Medical University of South Carolina, Charleston, South Carolina

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 melli-
tus, 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, debride-
ment, 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. Anti-
biotic 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 infec-
tions 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 infec-
tions. (Am Fam Physician. 2021;104(4):386-394. Copyright © 2021 American Academy of Family Physicians.)

Diabetes-related foot infections form in approxi- trauma and ultimately foot ulceration. Approximately 50%
mately 40% of foot ulcers in patients with diabetes melli- of patients with neuropathy are asymptomatic, making rec-
tus.1 Infections can rapidly progress to cellulitis, abscess ognition of a patient with an ulcer difficult.5 When the skin
formation, osteomyelitis, and necrotizing fasciitis. In 2016, ulcerates, an infection can develop rapidly because of cir-
diabetes-related foot infections contributed to more than culatory compromise and an impaired immune response.
130,000 lower-extremity amputations in the United States.2 Infection can spread rapidly to surrounding tissues, ini-
The five-year mortality rate following amputation is approx- tially causing cellulitis and later more severe complications
imately 50%, exceeding the mortality rate of many cancers.3 such as osteomyelitis and necrotizing fasciitis.6

Pathophysiology Microbiology
Patients with diabetes and vascular compromise, peripheral The most commonly isolated organisms from diabetes-related
neuropathy, and impaired immune function are at high risk foot infections are the gram-positive bacteria Staphylococcus
of developing foot infections. The risk increases with defor- aureus, Staphylococcus epidermidis, Streptococcus agalac-
mities (e.g., bunions, hammer toe, Charcot foot) that result tiae (i.e., group B Streptococcus), and Enterococcus species.
in high compressive forces in certain areas of the foot.4 Wounds infected by methicillin-resistant S. aureus (MRSA)
Peripheral neuropathy causes the loss of protective sensa- occur in approximately 15% of cases and are more serious
tion for pain and temperature and increases the risk of foot considering the virulence of MRSA and the limited number
of treatment options.7 Gram-negative bacteria are common
CME This clinical content conforms to AAFP criteria for
and isolated in more than one-half of samples, particularly
CME. See CME Quiz on page 338. the Enterobacteriaceae group and Pseudomonas aeruginosa.8
Author disclosure:​ No relevant financial affiliations. Anaerobes are present in about one-third of cultures. Bac-
Patient information:​ A handout on this topic is available at
teroides fragilis, Prevotella, Porphyromonas, and Clostridium
https://​w ww.aafp.org/afp/2013/0801/p177-s1.html. species are the most common.9 Approximately 50% to 80% of
infections are polymicrobial, which complicates treatment.10

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 DIABETES-RELATED FOOT INFECTIONS

Diagnostic Evaluation
Prompt diagnosis of a diabetes-related SORT:​KEY RECOMMENDATIONS FOR PRACTICE
foot infection decreases the risk of mor-
bidity and mortality. Family physicians Evidence
should consider patient risk factors Clinical recommendation rating Comments
(e.g., presence of foot ulcers greater Routine superficial wound cultures should B Systematic review and
than 2 cm, uncontrolled diabetes, poor not be performed because the results have meta-analysis of lower
vascular perfusion, comorbid illness) poor sensitivity and specificity for identify- quality diagnostic cohort
ing a pathogenic organism compared with studies
when assessing for infection. Findings deep tissue cultures.6,12
suggestive of infection include ery-
thema, induration, tenderness, warmth, Initial testing in patients with diabetes mel- B Lower quality diagnostic
litus and suspected osteomyelitis should cohort studies
and drainage. The probe-to-bone test is include plain radiography, a C-reactive pro-
an office maneuver that is 87% sensitive tein test, and probe-to-bone testing.6,11,15
and 83% specific for osteomyelitis.11
Empiric antibiotic therapy should target C Consensus guidelines and
A probe-to-bone test result is positive Streptococcus agalactiae and Staphylococ- inconsistent diagnostic
if insertion of a sterile and blunt metal cus aureus;​however, additional coverage cohort studies
instrument is met with hard or gritty should be considered based on local
resistance. An erythrocyte sedimenta- antimicrobial sensitivities, the severity of
infection, and patient factors.6-9
tion rate greater than 70 mm per hour
is also suggestive of osteomyelitis.4,6 Antibiotic coverage for methicillin-resistant B Lower quality diagnostic
Other causes of inflammation (e.g., S. aureus may be discontinued in a patient cohort studies
with a diabetes-related foot infection and
gout, rheumatoid arthritis, trauma)
a negative methicillin-resistant S. aureus
should be clinically ruled out. nares culture considering the high negative
Although an elevated white blood predictive value of this test.13,14
cell count can indicate a more severe
Secondary prevention of a foot infection B Systematic review of
infection, it is not often elevated with in a patient with diabetes should include lower quality clinical trials
a diabetes-related foot infection. systematic foot assessment, foot care and studies with inconsis-
C-reactive protein and procalcitonin counseling, use of appropriate footwear, tent findings
and comorbidity management.42-44
correlate better to soft tissue bacte-
rial infections than erythrocyte sed- A = consistent, good-quality patient-oriented evidence;​ B = inconsistent or limited-quality
imentation rate and white blood cell patient-oriented evidence;​ C = consensus, disease-oriented evidence, usual practice, expert
opinion, or case series. For information about the SORT evidence rating system, go to https://​
count. Routine superficial wound
6
www.aafp.org/afpsort.
cultures should be avoided because of
the high rate of contaminants;​how-
ever, deep tissue cultures obtained using aseptic procedures 10% to 40% of people with diabetes have peripheral arterial
(i.e., incision and drainage, debridement, and bone culture) disease.17 An ankle-brachial index is a quick and affordable
help guide treatment.6,12 A negative MRSA nares culture way to assess blood flow, but it can be inaccurate because
reduces the likelihood that a diabetes-related foot infection of arterial calcification with diabetes.16,18 Transcutaneous
is caused by MRSA. Studies have shown correlations with oximetry or arterial duplex ultrasonography may improve
negative predictive values between 73% and 90%.13,14 the accuracy of the vascular assessment.17,19 For more urgent
Plain radiography should be the initial imaging test if detection of arterial disease, magnetic resonance angiogra-
osteomyelitis is suspected.6,15 Osteomyelitis can take weeks phy with and without intravenous contrast media or a CT
to appear on radiographs;​therefore, magnetic resonance with intravenous contrast media is preferred. If a patient
imaging (MRI) or computed tomography (CT) is warranted is unable to receive intravenous contrast media because of
if a concern for osteomyelitis persists with normal radiogra- renal disease, duplex ultrasonography of the lower extrem-
phy findings. MRI helps detect soft tissue involvement and ity or magnetic resonance angiography without contrast
identifies the spatial orientation of infection to guide surgi- media are appropriate alternatives.20
cal planning. CT is appropriate if MRI is contraindicated.15
Vascular assessment should be performed on presenta- GRADING SEVERITY
tion, and patients with nonpalpable pulses should be for- In 2019, the International Working Group on the Diabetic
mally evaluated for arterial insufficiency.16 Approximately Foot published an update to the grading severity scale for

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 387
 DIABETES-RELATED FOOT INFECTIONS

diagnosing and classifying the extent

of diabetes-related foot infections. This TABLE 1
scale is the most validated scoring sys-
tem to grade the severity of the infec- International Working Group on the Diabetic Foot
tion and is summarized in Table 1.6 Classification System for Defining the Presence and Severity
The scale scores a foot ulcer from 1 to 4 of an Infection of the Foot in a Patient with Diabetes
(1 = uninfected, 2 = mild infection, Clinical classification of infection, with definitions IWGDF classification
3 = moderate infection, 4 = severe No systemic or local symptoms or signs of infection 1 (uninfected)
infection) and an “(O)” may follow Infected:​
scores 3 or 4 to indicate osteomyelitis.
At least two of these items are present:​
Erythema from a diabetes-related
Local swelling or induration
foot infection does not have to be con-
Erythema > 0.5 cm* around the wound
tiguous to a foot ulcer in the updated
Local tenderness or pain
classification scheme.6 Scores of 3
Local increased warmth
(odds ratio [OR] = 1.7) or 4 (OR = 2.5)
Purulent discharge
are associated with increased ampu-
tation rates.21 Other validated tools And no other cause of an inflammatory response of the skin
(e.g., trauma, gout, acute Charcot neuro-osteoarthropathy,
include the Site, Ischemia, Neurop- fracture, thrombosis, venous stasis)
athy, Bacterial Infection, and Depth
scoring system and the Wound, Isch- Infection with no systemic manifestations (see below) 2 (mild infection)
involving:​
emia, foot Infection scale, which help
Only the skin or subcutaneous tissue (not any deeper tissues)
predict outcomes and guide decisions
and
for surgical interventions.18,22 The Per-
Any erythema present does not extend > 2 cm† around the
fusion, Extent, Depth, Infection, and
wound
Sensation score is a validated scale
to predict amputation and mortal- Infection with no systemic manifestations and involving:​ 3 (moderate infection)
ity at six months and is available as Erythema extending ≥ 2 cm* from the wound margin,
an online calculator (https://​w ww. and/or
mdcalc.com/pedis-score-diabetic- Tissue deeper than skin and subcutaneous tissues
foot-ulcers).23,24 Figure 1 shows an (e.g., tendon, muscle, joint, bone)
uninfected ulcer, and Figure 2 shows Any foot infection with associated systemic manifestations 4 (severe infection)
an infected diabetes-related foot ulcer. (of the systemic inflammatory response syndrome [SIRS]), as
manifested by ≥ 2 of the following:​
Treatment Temperature > 38°C or < 36°C
ANTIBIOTIC THERAPY Heart rate > 90 beats per minute
Clinicians choosing antibiotics to Respiratory rate > 20 breaths per minute or PaCO 2
treat patients with a diabetes-related < 4.3 kPa (32 mm Hg)
foot infection should consider local White blood cell count > 12,000 per mm3, < 4,000 per
mm3, or > 10% immature (band) forms
antimicrobial sensitivities, the
severity of infection, patient factors Infection involving bone (osteomyelitis) Add “(O)” after 3 or 4‡
(e.g., drug-drug interactions, drug-
Note:​The presence of clinically significant foot ischemia makes both diagnosis and treatment
disease interactions, renal dysfunction, of infection considerably more difficult.
drug allergies), previous antibiotic kPa = kilopascal;​PaCO2 = partial pressure of carbon dioxide.
response, and patient preference. It is
*—Infection refers to any part of the foot, not just of a wound or an ulcer.
unclear if any one antibiotic is superior †—In any direction, from the rim of the wound.
for resolving an infection or safer than ‡—If osteomyelitis is demonstrated in the absence of ≥ 2 signs or symptoms of local or systemic
inflammation, classify the foot as either grade 3(O) (if < 2 SIRS criteria) or grade 4(O) (if ≥ 2 SIRS
other antibiotics.25 Empiric antibiotic
criteria).
coverage for a mild infection should
Reprinted with permission from Lipsky BA, Senneville É, Abbas ZG, et al.;​International Working
include S. aureus and S. agalactiae.6 Group on the Diabetic Foot (IWGDF). Guidelines on the diagnosis and treatment of foot infection
Guidelines also recommend empiric in persons with diabetes (IWGDF 2019 update). Diabetes Metab Res Rev. 2020;​36(suppl 1):​e3280.
coverage for MRSA. A negative MRSA

388 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 DIABETES-RELATED FOOT INFECTIONS

FIGURE 1 FIGURE 2

Uninfected diabetes-related plantar foot ulcer on the Infected diabetes-related foot ulcer in a patient with
fifth metatarsal head. Charcot foot.

nares culture may help clinicians de-escalate MRSA-specific Antibiotics may be needed for only a few days if osteomy-
coverage considering the high negative predictive value of elitis is surgically treated with amputation. Guidelines have
this test.6,13,14 Empiric antibiotic coverage for gram-negative recommended four to six weeks of antibiotics if osteomy-
rods (including P. aeruginosa) and anaerobes is reserved elitis is not treated surgically, but recent evidence suggests
for moderate or severe infections, recurrent infections, or three weeks of therapy may be similar to six weeks.4,6,30
infections with severe limb ischemia.6 Antibiotics used to Topical antibiotics are commonly applied to dressings for
treat diabetes-related foot infections are summarized in the prevention and treatment of mild diabetes-related foot
Table 2.26-28 infections. Resolution of a foot infection may be faster with
Oral antibiotics are appropriate for individuals with mild this approach, although the data supporting topical antibi-
infection and some moderate infections, whereas intrave- otics is weak and based on poorly designed trials.31
nous antibiotics are always needed initially for a severe infec-
tion, including individuals with osteomyelitis.4,6 After the SURGICAL TREATMENT
infection improves on intravenous antibiotics, it is reason- Surgical treatment plays a significant role in the manage-
able to switch to an oral antibiotic. Oral antibiotics can also ment of diabetes-related foot infection. Tissue and bone
be used for osteomyelitis after five to seven days of intrave- cultures obtained during surgical interventions help
nous coverage if the oral regimen has a high bioavailability.6 guide antibiotic selection. Many patients need sharp sur-
The optimal duration of antibiotic therapy for a diabetes- gical debridement by a wound care clinician or surgeon to
related foot infection depends on how quickly the infection remove necrotic tissue or calluses and aid in the formation
improves, the severity of infection, and patient factors (e.g., of granulation tissue capable of re-epithelialization.6 Shared
peripheral vascular disease, antibiotic adherence, adverse decision-making with patients is important because surgi-
antibiotic effects).29 Most patients should receive one to two cal procedures range from bedside debridement to major
weeks of antibiotics;​however, treatment could be extended amputation. Amputations are devastating psychologically,
to three to four weeks for slowly resolving infections.4,6 and many patients fear amputation more than death.32

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 389
 DIABETES-RELATED FOOT INFECTIONS

TABLE 2

Antibiotic Regimens and Treatment Considerations for Diabetes-Related Foot Infection

Infection severity Antibiotic therapy* Pathogen coverage Treatment considerations

Mild foot Cephalexin (Keflex), 500 mg GPC with or without First-line alternative for GBS or MSSA
infection orally every 6 hours GNR

Amoxicillin/clavulanate (Aug- GPC, GNR, First-line alternative, especially if concern for poly-
mentin), 875/125 mg orally every anaerobes microbial infection
12 hours

Trimethoprim/sulfamethoxazole, MSSA, MRSA, with or Use in combination with other antibiotics to cover
320/1,600 mg orally every 12 without GNR GBS;​may cause a rash, acute kidney injury, and
hours increased hyperkalemia risk

Doxycycline, 100 mg orally every MSSA, MRSA, with Use in combination with other antibiotics to cover
12 hours or without GNR, GBS;​causes photosensitivity and GI intolerance;​
anaerobes must be separated from di- and trivalent cations

Clindamycin, 300 to 450 mg GPC, with or Weaker coverage overall and can develop resis-
orally every 8 hours without MRSA, tance;​may be used in combination with other
anaerobes antibiotics to improve gram-negative coverage;​
causes GI intolerance and increased Clostridioides
difficile infection risk

Moderate foot Nafcillin, 1 to 2 g IV every 4 hours GPC First-line option given IV for GBS or MSSA
infection
Cefazolin, 1 to 2 g IV every 8 GPC, with or with- First-line option given IV for GBS or MSSA
hours out GNR

Vancomycin loading dose, 20 to GPC including MRSA Drug of choice given IV for MRSA;​requires ther-
30 mg per kg IV, then based on apeutic drug monitoring for effectiveness and
local institutional policy nephrotoxicity concern

Ampicillin/sulbactam (Unasyn), GPC, GNR, Good option for more severe infections, but does
3 g IV every 6 hours anaerobes not cover Pseudomonas

Ertapenem (Invanz), 1 g IV every GPC, GNR, Alternative option if needing treatment IV once per
24 hours anaerobes day

Ceftriaxone, 1 to 2 g IV every GPC, GNR Good option for more severe infections, but does
24 hours not cover Pseudomonas;​often combined with met-
ronidazole (Flagyl) to improve anaerobic coverage

Metronidazole, 500 mg IV vs. Anaerobes Often used in combination with other antibiotics to
500 mg orally every 8 hours improve anaerobic coverage;​avoid alcohol

Levofloxacin (Levaquin), 750 mg GPC, GNR Less preferred with multiple precautions (e.g.,
IV or 750 mg orally every 24 including Pseudo- QTc prolongation, tendon rupture, hypoglycemia
hours monas aeruginosa, or hyperglycemia, aortic aneurism or dissection,
ESBL-producing peripheral or optic neuropathy, seizure);​must be
organism separated from di- and trivalent cations

Delafloxacin (Baxdela), 300 mg GPC, MRSA, GNR See levofloxacin precautions, which are class
IV every 12 hours or 450 mg including P. aerugi- warnings
orally every 12 hours nosa, anaerobes

continues

ESBL = extended-spectrum beta-lactamase;​GBS = group B Streptococcus;​GI = gastrointestinal;​GNR = gram-negative rods;​GPC = gram-positive

cocci;​IV = intravenously;​MRSA = methicillin-resistant Staphylococcus aureus;​MSSA = methicillin-sensitive S. aureus.
*—Indicates typical dosing recommendations; however, dose adjustments for hepatic and renal function and local institutional policies may
change these recommended doses.

390 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 DIABETES-RELATED FOOT INFECTIONS

TABLE 2 (continued)

Antibiotic Regimens and Treatment Considerations for Diabetes-Related Foot Infection

Infection severity Antibiotic therapy* Pathogen coverage Treatment considerations

Severe foot Vancomycin loading dose, 20 to GPC including MRSA Drug of choice given IV for MRSA;​requires ther-
infection 30 mg per kg IV, then based on apeutic drug monitoring for effectiveness and
local institutional policy nephrotoxicity concern

Daptomycin (Cubicin), 4 to 6 mg GPC including MRSA Alternative option to vancomycin given IV for MRSA;​
per kg IV every 24 hours (may requires baseline and weekly creatine kinase moni-
increase to 8 to 10 mg per kg for toring for rhabdomyolysis
a bone or joint infection)

Linezolid (Zyvox), 600 mg IV GPC including MRSA Alternative option to vancomycin given IV for
every 12 hours (also available MRSA;​requires complete blood count monitoring if
as a 600-mg tablet if patient is treatment > 2 weeks with pancytopenia risk;​watch
stable enough for oral therapy) drug-drug interactions that could cause serotonin
syndrome

Piperacillin/tazobactam (Zosyn), GPC, GNR includ- Often a drug of choice with broad empiric coverage;​
4.5 g IV every 6 hours ing P. aeruginosa, could cause acute kidney injury risk especially in
anaerobes combination with other nephrotoxins

Cefepime, 2 g IV every 8 hours GPC, GNR including Good alternative to piperacillin/tazobactam if con-
P. aeruginosa cern for acute kidney injury;​often combined with
metronidazole to improve anaerobic coverage

Meropenem (Merrem IV), 1 g IV GPC, ESBL-produc- Treatment of choice with ESBL-producing organism
every 8 hours ing organism, GNR or if other broad-spectrum gram-negative coverage
including P. aerugi- is ineffective
nosa, anaerobes

ESBL = extended-spectrum beta-lactamase;​GBS = group B Streptococcus;​GI = gastrointestinal;​GNR = gram-negative rods;​GPC = gram-positive

cocci;​IV = intravenously;​MRSA = methicillin-resistant Staphylococcus aureus;​MSSA = methicillin-sensitive S. aureus.
*—Indicates typical dosing recommendations; however, dose adjustments for hepatic and renal function and local institutional policies may
change these recommended doses.
Information from references 26-28.

Surgical intervention is needed for gangrene, necrotizing OTHER THERAPIES

fasciitis, or significant abscess formation. Although surgical Wound therapy in a patient with a diabetes-related foot
resection of osteomyelitis was traditionally the standard of infection is complex and often requires team-based care.
care, emerging evidence suggests most infections respond Comprehensive wound care may include debridement,
well to antibiotic therapy alone.6 application of moist dressings, and the use of off-loading
In patients with a diabetes-related foot infection and orthotics to reduce pressure on a wound.6 A moist dressing
ischemia, vascular interventions should be considered to is preferred to aid in healing and help with infection con-
improve a patient’s treatment response and lower the risk of trol. It is unknown if any specific dressing is more effective
recurrence.17 The Wound, Ischemia, foot Infection score pre- because of a lack of head-to-head trials.35 Redistribution of
dicts clinical outcomes and guides interventions in patients pressure off the plantar surface is important because this
with more advanced disease.33,34 The Wound, Ischemia, foot is the main cause of foot ulcers and, if not addressed, may
Infection scoring system factors in the International Work- inhibit ulcer healing. Strategies to help with off-loading
ing Group on the Diabetic Foot infection grade, objective pressure include changes to a patient’s shoes, specialized
measures to determine the extent of ischemia, and the antic- boots, or orthotic walkers.36
ipated likelihood of wound healing. These factors combine to Studies of adjunctive treatments (e.g., hyperbaric oxygen
stage wounds from 0 to 3 with higher scores requiring more therapy, maggot debridement therapy, granulocyte colony-
invasive surgical management, including amputation.18 stimulating factors, topical oxygen therapy, laser therapy)

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 391
 DIABETES-RELATED FOOT INFECTIONS

for healing diabetes-related foot ulcers have mixed results. (e.g., severe neuropathy, foot deformities, ulcers, poor circu-
Of these alternative treatments, hyperbaric oxygen therapy lation, history of amputation).43
has the best data, with evidence showing that it lowers the Other preventive techniques include improving glucose
risk of major amputations and improves wound healing;​ control, smoking cessation, daily foot inspection, debride-
however, evidence does not support reductions in minor ment of calluses, and monthly physician foot checks for
amputations or mortality.37 Maggot debridement therapy patients with end-stage renal disease requiring dialysis.42-45
has good data, with evidence for shortening ulcer
healing time and reducing the rate of amputa-
tions.38 Granulocyte colony-stimulating factors TABLE 3
have not been shown to help resolve an infection
Recommendations for Preventing Diabetes-Related
or foot ulcer significantly, but they may decrease
Foot Infections
the risk of surgical interventions and amputa-
tions. Promising evidence exists for topical
39 Prevention
oxygen therapy and laser therapy for improv- strategy Counseling recommendations
ing diabetes-related foot ulcer healing;​however, Control Delay progression of kidney disease to end-stage renal
more evidence is needed on patient-oriented comorbidities disease, or if end-stage renal disease is present, conduct
outcomes before widespread adoption of either monthly foot checks during hemodialysis sessions or
while in clinic
intervention. 40,41
Improve glycemic control

Prevention Optimize peripheral vascular disease with antiplatelet

therapy, statins, and vascular surgery as needed
Little evidence exists for primary prevention Smoking cessation as needed
strategies of diabetes-related foot ulcers or
infections despite widespread support for these Proper Apply moisturizers after bathing to prevent blisters,
foot care cracks, and calluses, although avoid applying moistur-
interventions.42 Guidelines strongly support sys- education izer between the toes
tematic assessment, foot care counseling, and
Avoid walking barefoot even when indoors
comorbidity management for primary preven-
Check daily for foot pain, redness, abrasions, or infec-
tion because these strategies are useful in sec- tions on the plantar foot and between toes (may require
ondary prevention, and complications from a use of a mirror or caregiver)
diabetes-related foot infection are significant.6,43 Contact a primary care physician or podiatrist if finding
Recognition of a patient with neuropathy is crit- a foot abnormality
ical considering the high rate of patients who are Debride calluses to improve foot sensation and prevent
asymptomatic. Conducting a foot examination ulcer formation under a callus

may take only three minutes and can be orga- Trim nails straight across, then smooth with a nail file
(avoid cutting into the corners of toes)
nized into three parts (patient history, physical
Wash feet regularly and dry feet after a bath or exercise
examination, patient education).5 Team-based
Wear comfortable shoes and check the inside of shoes
care for primary prevention may include nurses,
before use
pharmacists, podiatrists, and other clinicians.
Secondary prevention of diabetes-related foot Select Avoid sandals
appropriate
ulcers and infections starts with frequent, sys- footwear
Avoid shoes that are too tight, too small, or cause fric-
tion on a part of the foot
tematic assessments recommended by guidelines
Choose broad footwear with a square toe box, laces
such as the American Diabetes Association’s
with 3 to 4 eyes per slide, padded shoe tongue, well-
Standards of Medical Care. These guidelines made but lightweight materials, and shoes large enough
highlight the importance of a comprehensive foot to accommodate a cushioned insole
examination at least annually, and for every dia- Replace shoes at least yearly, but more frequently if they
betes care visit for individuals at high risk of an exhibit wear
infection (e.g., poor circulation, history of ampu- Use specialized footwear in patients with severe neu-
tation, severe neuropathy).43 All patients with ropathy, foot deformities, calluses, poor foot circulation,
ulcers, or history of amputation
diabetes should receive counseling on foot care
Wear socks at all times and change socks at least daily
and how to choose appropriate footwear. Using
therapeutic footwear is often unnecessary;​how- Information from references 5 and 42-45.
ever, it should be considered in high-risk patients

392 American Family Physician www.aafp.org/afp Volume 104, Number 4 ◆ October 2021
 DIABETES-RELATED FOOT INFECTIONS

Interventions to prevent an ulcer or diabetes-related foot 8. Henig O, Pogue JM, Cha R, et al. Epidemiology of diabetic foot infec-
tion in the metro-Detroit area with a focus on independent predictors
infections are summarized in Table 3.5,42-45 for pathogens resistant to recommended empiric antimicrobial ther-
apy. Open Forum Infect Dis. 2018;​5(11):​ofy245.
This article updates previous articles on this topic by Gemechu,
et al., 27 and Bader. 26 9. Citron DM, Goldstein EJ, Merriam CV, et al. Bacteriology of moderate-
to-severe diabetic foot infections and in vitro activity of antimicrobial
Data Sources:​ A PubMed search was completed in Clinical Que- agents. J Clin Microbiol. 2007;​45(9):​2819-2828.
ries using the key terms diabetic foot ulcers, infections, antibi-
10. Sadeghpour Heravi F, Zakrzewski M, Vickery K, et al. Bacterial diversity
otics, statistics, pharmacological, and prevention. The search of diabetic foot ulcers:​current status and future prospectives. J Clin
included meta-analyses, randomized controlled trials, clinical Med. 2019;​8(11):​1935.
trials, and reviews. Also searched were Access Medicine, the
11. Lam K, van Asten SAV, Nguyen T, et al. Diagnostic accuracy of probe to
Cochrane Library, Lexicomp, the National Guideline Clearing- bone to detect osteomyelitis in the diabetic foot:​a systematic review.
house database, and UpToDate. Search dates:​October 27, 2020 Clin Infect Dis. 2016;​63(7):​944-948.
to November 4, 2020, and April 26, 2021.
12. Chakraborti C, Le C, Yanofsky A. Sensitivity of superficial cultures in
Figures 1 and 2 provided courtesy of Joshua Visserman, MD. lower extremity wounds. J Hosp Med. 2010;​5(7):​415-420.
13. Acquisto NM, Bodkin RP, Brown JE, et al. MRSA nares swab is a more
accurate predictor of MRSA wound infection compared with clinical
The Authors risk factors in emergency department patients with skin and soft tissue
infections. Emerg Med J. 2018;​35(6):​357-360.
ERIC M. MATHESON, MD, MS, is the transitional year resi-
dency director and associate professor in the Department of 14. Mergenhagen KA, Croix M, Starr KE, et al. Utility of methicillin-resistant
Family Medicine at the Medical University of South Carolina, Staphylococcus aureus nares screening for patients with a diabetic foot
infection. Antimicrob Agents Chemother. 2020;​6 4(4):​e02213-e02219.
Charleston.
15. Walker EA, Beaman FD, Wessell DE, et al.;​Expert Panel on Musculo-
SCOTT W. BRAGG, PharmD, BCPS, is an associate professor skeletal Imaging. ACR appropriateness criteria. Suspected osteomyelitis
in the Department of Family Medicine and the Department of the foot in patients with diabetes mellitus. J Am Coll Radiol. 2019;​
16(11S):​S 440-S450.
of Clinical Pharmacy and Outcomes Sciences at the Medical
University of South Carolina. 16. Bandyk DF. The diabetic foot:​pathophysiology, evaluation, and treat-
ment. Semin Vasc Surg. 2018;​31(2-4):​43-48.
RUSSELL S. BLACKWELDER, MD, MDiv, CMD, is the director of 17. Hart T, Milner R, Cifu A. Management of the diabetic foot. JAMA. 2017;​
Geriatric Education and assistant professor in the Department 318(14):​1 387-1388.
of Family Medicine at the Medical University of South Carolina. 18. Mills JL Sr., Conte MS, Armstrong DG, et al.;​Society for Vascular Surgery
Lower Extremity Guidelines Committee. The Society for Vascular Sur-
Address correspondence to Eric M. Matheson, MD, MS, 9228 gery Lower Extremity threatened limb classification system:​risk stratifi-
Medical Plaza Dr., Charleston, SC 29406 (email:​matheson@​ cation based on wound, ischemia, and foot infection (WIfI). J Vasc Surg.
musc.edu). Reprints are not available from the authors. 2014;​59(1):​220-234.e1-2.
19. Fagher K, Katzman P, Löndahl M. Transcutaneous oxygen pressure as
a predictor for short-term survival in patients with type 2 diabetes and
References foot ulcers:​a comparison with ankle-brachial index and toe blood pres-
1. Jia L, Parker CN, Parker TJ, et al.;​Diabetic Foot Working Group, sure. Acta Diabetol. 2018;​55(8):​781-788.
Queensland Statewide Diabetes Clinical Network (Australia). Incidence 20. Ahmed O, Hanley M, Bennett SJ, et al.;​Expert Panel on Vascular Imag-
and risk factors for developing infection in patients presenting with ing. ACR appropriateness criteria. Vascular claudication-assessment for
uninfected diabetic foot ulcers. PLoS One. 2017;​1 2(5):​e0177916. revascularization. J Am Coll Radiol. 2017;​14(5S):​S372-S379.
2. Centers for Disease Control and Prevention. National diabetes statis- 21. Sen P, Demirdal T, Emir B. Meta-analysis of risk factors for amputation in
tics report, 2020. Accessed October 20, 2020. https://​w ww.cdc.gov/ diabetic foot infections. Diabetes Metab Res Rev. 2019;​35(7):​e3165.
diabetes/pdfs/data/statistics/national-diabetes-statistics-report.pdf
22. Ince P, Abbas ZG, Lutale JK, et al. Use of the SINBAD classification sys-
3. Armstrong DG, Swerdlow MA, Armstrong AA, et al. Five year mortality tem and score in comparing outcome of foot ulcer management on
and direct costs of care for people with diabetic foot complications are three continents. Diabetes Care. 2008;​31(5):​964-967.
comparable to cancer. J Foot Ankle Res. 2020;​1 3(1):​16.
23. Chuan F, Tang K, Jiang P, et al. Reliability and validity of the perfusion,
4. Lipsky BA, Berendt AR, Cornia PB, et al.;​Infectious Diseases Society of extent, depth, infection and sensation (PEDIS) classification system
America. 2012 Infectious Diseases Society of America clinical practice and score in patients with diabetic foot ulcer. PLoS One. 2015;​10(4):​
guideline for the diagnosis and treatment of diabetic foot infections. e0124739.
Clin Infect Dis. 2012;​5 4(12):​e132-e173.
24. Chuan F. PEDIS score for diabetic foot ulcers. MDCalc. Accessed Decem-
5. Miller JD, Carter E, Shih J, et al. How to do a 3-minute diabetic foot
ber 30, 2020. https://​w ww.md​calc.com/pedis-​score-​diabetic-​foot-​
exam [published correction appears in J Fam Pract. 2015;​6 4(8):​452].
ulcers​
J Fam Pract. 2014;​63(11):​6 46-656.
25. Selva Olid A, Solà I, Barajas-Nava LA, et al. Systemic antibiotics for
6. Lipsky BA, Senneville É, Abbas ZG, et al.;​International Working Group
treating diabetic foot infections. Cochrane Database Syst Rev. 2015;​(9):​
on the Diabetic Foot (IWGDF). Guidelines on the diagnosis and treat-
CD009061.
ment of foot infection in persons with diabetes (IWGDF 2019 update).
Diabetes Metab Res Rev. 2020;​36(suppl 1):​e3280. 26. Bader MS. Diabetic foot infection. Am Fam Physician. 2008;​78(1):​71-79.
7. Reveles KR, Duhon BM, Moore RJ, et al. Epidemiology of methicillin- Accessed April 6, 2021. https://​w ww.aafp.org/afp/2008/0701/p71.html
resistant Staphylococcus aureus diabetic foot infections in a large aca- 27. Gemechu FW, Seemant F, Curley CA. Diabetic foot infections. Am Fam
demic hospital:​implications for antimicrobial stewardship. PLoS One. Physician. 2013;​
88(3):​
177-184. Accessed April 6, 2021. https://​w ww.
2016;​1 1(8):​e0161658. aafp.org/afp/2013/0801/p177.html

October 2021 ◆ Volume 104, Number 4 www.aafp.org/afp American Family Physician 393
 DIABETES-RELATED FOOT INFECTIONS

28. Lexicomp. Accessed October 27, 2020. https://​online.lexi.com/lco/ 37. Sharma R, Sharma SK, Mudgal SK, et al. Efficacy of hyperbaric oxygen
action/login therapy for diabetic foot ulcer, a systematic review and meta-analysis of
29. Dudareva M, Kümin M, Vach W, et al. Short or long antibiotic regimes controlled clinical trials. Sci Rep. 2021;​1 1(1):​2189.
in orthopaedics (SOLARIO):​a randomised controlled open-label non- 38. Sun X, Jiang K, Chen J, et al. A systematic review of maggot debride-
inferiority trial of duration of systemic antibiotics in adults with ortho- ment therapy for chronically infected wounds and ulcers. Int J Infect
paedic infection treated operatively with local antibiotic therapy. Trials. Dis. 2014;​25:​32-37.
2019;​20(1):​693. 39. Cruciani M, Lipsky BA, Mengoli C, et al. Granulocyte-colony stimulat-
30. Gariani K, Pham TT, Kressmann B, et al. Three versus six weeks of antibi- ing factors as adjunctive therapy for diabetic foot infections. Cochrane
otic therapy for diabetic foot osteomyelitis:​a prospective, randomized, Database Syst Rev. 2013;​(8):​CD006810.
non-inferiority pilot trial. Clin Infect Dis. 2020;​ciaa1758. 40. Thanigaimani S, Singh T, Golledge J. Topical oxygen therapy for
31. Dumville JC, Lipsky BA, Hoey C, et al. Topical antimicrobial agents for diabetes-related foot ulcers:​a systematic review and meta-analysis.
treating foot ulcers in people with diabetes. Cochrane Database Syst Diabet Med. 2021;​e14585.
Rev. 2017;​(6):​CD011038. 41. Huang J, Chen J, Xiong S, et al. The effect of low-level laser therapy on
32. Wukich DK, Raspovic KM, Suder NC. Patients with diabetic foot disease diabetic foot ulcers:​a meta-analysis of randomised controlled trials. Int
fear major lower-extremity amputation more than death. Foot Ankle Wound J. March 9, 2021. Accessed April 25, 2021. https://​onlinelibrary.
Spec. 2018;​1 1(1):​17-21. wiley.com/doi/epdf/10.1111/iwj.13577
33. Zhan LX, Branco BC, Armstrong DG, et al. The Society for Vascular 42. van Netten JJ, Price PE, Lavery LA, et al.;​International Working Group
Surgery lower extremity threatened limb classification system based on the Diabetic Foot. Prevention of foot ulcers in the at-risk patient with
on wound, ischemia, and foot infection (WIfI) correlates with risk of diabetes:​a systematic review. Diabetes Metab Res Rev. 2016;​32(suppl 1):​
major amputation and time to wound healing. J Vasc Surg. 2015;​61(4):​ 84-98.
939-944. 43. American Diabetes Association. Microvascular complications and foot
34. Peripheral Vascular Diagnosis Made Intelligent. WIfI classification sys- care:​standards of medical care in diabetes–2020. Diabetes Care. 2020;​
tem. Accessed December 30, 2020. https://​w ww.perimed-instruments. 43(suppl 1):​S135-S151.
com/content/wifi-classification-system/ 44. Xiang J, Wang S, He Y, et al. Reasonable glycemic control would help
35. Vas P, Rayman G, Dhatariya K, et al. Effectiveness of interventions to wound healing during the treatment of diabetic foot ulcers. Diabetes
enhance healing of chronic foot ulcers in diabetes:​a systematic review. Ther. 2019;​10(1):​95-105.
Diabetes Metab Res Rev. 2020;​36(suppl 1):​e3284. 45. Marn Pernat A, Peršič V, Usvyat L, et al. Implementation of routine foot
36. Everett E, Mathioudakis N. Update on management of diabetic foot check in patients with diabetes on hemodialysis:​associations with out-
ulcers. Ann N Y Acad Sci. 2018;​1411(1):​153-165. comes. BMJ Open Diabetes Res Care. 2016;​4(1):​e000158.

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