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August 1, 2013 Volume 88, Number 3 www.aafp.org/afp American Family Physician 177
Diabetic Foot InfectionsFASSIL W. GEMECHU, MD, MetroHealth Medical Center, Cleveland, Ohio
FNU SEEMANT, MD, State University of New York at Buffalo, Buffalo, New YorkCATHERINE A. CURLEY, MD, MetroHealth Medical Center, Cleveland, Ohio
Diabetic foot infections, whichare infections of the soft tissueor bone below the malleoli, are acommon clinical problem. Most
infections occur in a site of skin trauma orulceration. The estimated lifetime risk of aperson with diabetes mellitus developinga foot ulcer is 15% to 25%, with an annualincidence of 3% to 10%. 1 Major predisposingfactors are peripheral neuropathy, peripheralarterial disease, and impaired immunity.More than one-half of nontraumatic lowerextremity amputations are related to dia-betic foot infections, and 85% of all lowerextremity amputations in patients with dia-
betes are preceded by an ulcer.2,3
The most common pathogens in dia-betic foot infection are aerobic gram-positive cocci, mainly Staphylococcusspecies. Methicillin-resistant Staphylococcusaureus is present in 10% to 32% of diabeticinfections and is associated with a higherrate of treatment failure in patients withdiabetic foot infection. 4 Moderate to severeinfections and wounds previously treatedwith antibiotics are often polymicrobial,including gram-negative bacilli. Anaerobicpathogens are more commonly present in
necrotic wounds and infections of the isch-emic foot.
How Is Diabetic Foot InfectionDiagnosed?Diabetic foot infection is a clinical diagnosisbased on the presence of at least two classic ndings of inammation or purulence. 2,5,6
SUPPORTING EVIDENCE
Evaluation of a suspected diabetic foot infec-tion should involve a thorough assessment ofthe wound, the limb, and the patients over-all health. Local signs of infection includeredness, warmth, induration or swelling,
pain or tenderness, and purulent secretions.Failure of a wound to heal in spite of propertreatment, and the presence of nonpurulentdischarge, malodor, and necrotic or friabletissue also suggest infection. 7
The Infectious Diseases Society of Amer-ica and the International Working Group onthe Diabetic Foot classify diabetic woundsas uninfected or infected, with mild,moderate, and severe grades of infection(Table 17). This classication system was pro-spectively validated in a longitudinal studyof 1,666 patients and was found to reliably
Diabetic foot infection, dened as soft tissue or bone infection below the malleoli, is the most common complica-tion of diabetes mellitus leading to hospitalization and the most frequent cause of nontraumatic lower extremityamputation. Diabetic foot infections are diagnosed clinically based on the presence of at least two classic ndings ofinammation or purulence. Infections are classied as mild, moderate, or severe. Most diabetic foot infections arepolymicrobial. The most common pathogens are aerobic gram-positive cocci, mainly Staphylococcus species. Osteo-myelitis is a serious complication of diabetic foot infection that increases the likelihood of surgical intervention.Treatment is based on the extent and severity of the infection and comorbid conditions. Mild infections are treated with oral antibiotics, wound care, and pressure off-loading in the outpatient setting. Selected patients with moderate
infections and all patients with severe infections should be hospitalized, given intravenous antibiotics, and evaluatedfor possible surgical intervention. Peripheral arterial disease is present in up to 40% of patients with diabetic footinfections, making evaluation of the vascular supply critical. All patients with diabetes should undergo a systematicfoot examination at least once a year, and more frequently if risk factors for diabetic foot ulcers exist. Preventivemeasures include patient education on proper foot care, glycemic and blood pressure control, smoking cessation,use of prescription footwear, intensive care from a podiatrist, and evaluation for surgical interventions as indicated.( Am Fam Physician. 2013;88(3):177-184. Copyright 2013 American Academy of Family Physicians.)
Patient informa-tion: A handout on thistopic, written by theauthors of this article, isavailable at http://www.aafp.org/afp/2013/0801/p177-s1.html. Access tothis handout is free andunrestricted.
CME This clinical contentconforms to AAFP criteriafor continuing medicaleducation (CME). See CMEQuiz on page 162.
Author disclosure: No rel-evant nancial afliations.
Downloaded from the American Family Physician website at www.aafp.org/afp. Copyright 2013 American Academy of Family Physicians. For the private, noncommercial use of one individual user of the website. All other rights reserved. Contact [email protected] for copyright questions and/or permission requests.
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underlying bony abnormalities because ittakes weeks for bone infection to becomeradiographically apparent 10 (Table 2 2,7,14).
Triple phase technetium-99m methylenediphosphonate bone scan is more sensitivethan plain radiography, with a sensitivity ofabout 90%, but it has a much lower specic-ity (46%). White blood cell scans are morespecic than tr iple phase bone scan and maybe useful when magnetic resonance imagingis not available or is contraindicated. 14-16
Magnetic resonance imaging is the mostaccurate imaging study in the diagnosis ofosteomyelitis. 10-12 It is 90% sensitive and 80%specic.11 However, it may be of limited value
in differentiating osteomyelitis from acuteCharcot neuroarthropathy. 17
Probe-to-bone testing (attempting toreach exposed bone with a metal probe) isan inexpensive diagnostic tool used to sup-port the diagnosis of osteomyelitis. It shouldbe performed after debridement of devital-ized and necrotic tissue. A positive result onprobe-to-bone testing (touching a hard orgritty bone surface) increases the likelihoodof osteomyelitis in patients with high pre-test probability. A negative result on probe-to-bone testing in patients with low pretestprobability makes osteomyelitis unlikely butdoes not exclude the diagnosis. 18-20 A study ofoutpatients with diabetic foot ulcers foundprobe-to-bone testing to be 87% sensitiveand 91% specic for osteomyelitis. 19
What Is the Value of Blood Testingin the Diagnosis of Diabetic FootInfections?Leukocytosis and elevated erythrocyte sedi-
mentation rate increase the risk of a diabetic foot infection, but their absence does not ruleit out.
SUPPORTING EVIDENCE
In one multicenter study, investigators foundthat more than one-half of the patientsadmitted with acute diabetic foot infectionhad a normal leukocyte count, and 83.7%had a normal neutrophil count. 21 The absenceof leukocytosis, an absence of a left shift in awhite blood cell differential, or lack of eleva-tion of acute phase reactants does not exclude
infection. An erythrocyte sedimentation rategreater than 70 mm per hour in combinationwith clinical suspicion has been shown to
correlate with increased likelihood of osteo-myelitis. Conversely, a normal erythrocytesedimentation rate lessens the likelihood ofosteomyelitis but does not exclude it. 22
Erythrocyte sedimentation rate andC-reactive protein are helpful biochemi-cal markers to monitor therapeuticresponse. 10,11,14-20,22-24 Blood cultures shouldbe obtained in patients with severe diabeticfoot infections.
How Should Diabetic Foot Infections
Be Treated?Treatment of a diabetic foot infection is basedon the extent and severity of the infection. No
Table 2. Common Radiographic Findings in Patientswith Diabetic Foot Infections
Plain radiographyPeriosteal reaction or elevationLoss of cortex with bony erosionFocal loss of trabecular pattern or marrow radiolucencyNew bone formationBone sclerosis with or without erosionSequestrum: devitalized bone with radiodense appearance that has
become separated from normal boneInvolucrum: a layer of new bone growth outside existing bone resulting
from the stripping off of the periosteum and new bone growing fromthe periosteum
Cloacae: opening in involucrum or cortex through which sequestra orgranulation tissue may be discharged
Magnetic resonance imagingMore specic changes
Low focal signal intensity on T1-weighted imagesHigh focal signal on T2-weighted imagesHigh bone marrow signal in short tau inversion recovery sequences
Less specic or secondary changesAdjacent cutaneous ulcerAdjacent soft tissue inammation or edemaCortical disruptionSinus tract formationSoft tissue mass
NOTE:For both modalities, bony changes are often accompanied by contiguous softtissue swelling.
Information from references 2, 7, and 12.
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single antibiotic regimen is clearly superiorto another. Mild infections should be treatedwith oral antibiotics in the outpatient setting.
Selected patients with moderate infectionsand all patients with severe infections requirehospitalization to receive parenteral antibi-otics, surgical consultation, and additionalevaluation.
SUPPORTING EVIDENCE
Care provided by a well-coordinated, multi-disciplinary team has been shown to improveoutcomes in diabetic foot infections. 25,26 TheNational Institute for Health and Clinical
Excellence guidelines on the inpatient man-agement of diabetic foot problems recom-mend that each hospital have a care pathway
carried out by a multidisciplinary team.16
Initial choice of empiric antibiotic is basedon severity of infection and the likely patho-gen (Table 3 2,7,27). Mild infections with noprior antibiotic therapy should be treatedwith one to two weeks of oral antibiotics thatcover aerobic gram-positive pathogens. 27-29 Selected patients with moderate infections(patients with poor glycemic control orperipheral arterial disease, and patients whoare unable to adhere to a treatment plan that
Table 3. Suggested Antibiotics for Treatment of Diabetic Foot Infection
Pathogen Empiric antibiotic Active againstMRSA?
Duration ofinitial therapy
Renal doseadjustment?
Mild infection 1 to 2 weeksGram-positive cocci with or
without MRSAAmoxicillin/clavulanate (Augmentin) No YesCefdinir (Omnicef) No YesCephalexin (Keex) No YesClindamycin* Yes NoDicloxacillin (Dynapen) No No
Doxycycline Yes NoLevooxacin (Levaquin) No YesLinezolid (Zyvox) Yes (use if high
risk for MRSA)No
Minocycline (Minocin) Yes YesTrimethoprim/sulfamethoxazole Yes Yes
Moderate to severe infection 2 to 3 weeksGram-positive cocci; gram-negative
rods; anaerobes with or withoutmultidrug-resistant organisms(e.g., MRSA, extended-spectrumbeta-lactamaseproducingstrains, vancomycin-resistant
enterococcus)
Ampicillin/sulbactam (Unasyn) No YesCefoxitin No YesCeftriaxone (Rocephin) No NoClindamycin/uoroquinolones Somewhat No/YesDaptomycin (Cubicin) Yes Yes
Ertapenem (Invanz) No YesImipenem/cilastin (Primaxin) No YesLinezolid Yes NoMoxioxacin (Avelox) No NoPiperacillin/tazobactam (Zosyn) No YesTicarcillin/clavulanate (Timentin) No YesTigecycline (Tygacil) Yes NoVancomycin Yes Yes
MRSA = methicillin-resistant Staphylococcus aureus .
*Consider a double disk diffusion test before using for MRSA.
Information from references 2, 7, and 27.
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includes antibiotic use, appropriate woundcare, pressure off-loading, and return forclose follow-up) and all patients with severeinfections require hospital admission andtreatment with broad-spectrum parenteralantibiotics. Surgical interventions mayinclude incision and drainage of an abscess,extensive debridement of necrotic and devi-talized tissue, resection, amputation, andrevascularization, and should be performedin a timely manner. 30-32
The suggested duration of antibiotics formoderate to severe soft tissue infections istwo to three weeks. Traditionally, the dura-tion of antibiotic therapy for diabetic footosteomyelitis has been prolonged, but per-sons in whom the infected bone was surgi-cally removed can be treated with a shortercourse (Table 4 2).
A recent systematic review of several ran-domized controlled and cohort studies bythe International Working Group on the
Diabetic Foot comparing different antibioticregimens showed there was no one superiorregimen, route of administration, or dura-tion of treatment for diabetic foot infec-tions. 13 The Infectious Diseases Society ofAmerica guidelines on diabetic foot infec-tion reached the same conclusion. 2
Beyond the initial treatment phase, subse-quent choice of antibiotics should be guidedby the extent of infection, culture results,and the clinical response to empiric therapy(Figure 1 7). Physicians should also considerlocal antibiotic resistance patterns and the
presence of multidrug-resistant organisms,renal and hepatic impairment, drug aller-gies, immunosuppression, patient compli-ance, and cost of treatment. 6,12
What Is the Role of Peripheral ArterialDisease in Diabetic Foot Infections?Peripheral arterial disease is an independentrisk factor for diabetic foot infections and isthe most important predictor of the outcome ofdiabetic foot ulceration.33
SUPPORTING EVIDENCE
Peripheral arterial disease is present in upto 40% of patients with diabetic foot infec-tions. 34 In spite of advancements in medicaland surgical therapies, the risks of amputa-tion and the ve-year mortality rate afteramputation remain high. 35 Evaluation ofthe vascular supply is critical in the treat-ment of diabetic foot infection. Examinationshould include the color and temperature of
the skin, palpation of peripheral pulses, andsigns of arterial insufciency, including skinand nail atrophy. An ankle-brachial indexbelow 0.9 indicates occlusive arterial disease;an index below 0.5 is consistent with signi-cant peripheral arterial disease. 33 Additionalevaluation that includes toe blood pressuremeasurement, transcutaneous pressure ofoxygen, or arterial Doppler examinationmay be warranted. Computed tomographyangiography and magnetic resonance angi-ography are most useful in patients who arecandidates for revascularization. 36
Table 4. Suggested Route of Administration and Duration of Antibiotic Therapyfor Diabetic Foot Osteomyelitis
Bone or joint infection Route of administration Duration of therapy
No residual infected tissue (e.g., postamputation) Parenteral or oral 2 to 5 daysResidual infected soft tissue (but not bone) Parenteral or oral 1 to 3 weeksResidual infected (but viable) bone Initially parenteral, then
consider oral4 to 6 weeks
No surgery, or residual dead bone postoperatively Initially parenteral, thenconsider oral
3 months
Adapted with permission from Lipsky BA, Berendt AR, Cornia PB, et al.; Infec tious Diseases Society of America. 2012Infectious Diseases Society of America clinical practice guideline for the diagnosis and treatment of diabetic foot infec-tions. Clin Infect Dis. 2012;54(12):e158.
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Approach to the Infected Diabetic Foot
Figure 1. Algorithmic approach to the assessment and treatment of diabetic foot infections. Adapted with permission from Lipsky BA, Peters EJ, Senneville E, et al. Expert opinion on the management of infections in the diabetic foot. Diabetes MetabRes Rev. 2012;28(suppl 1):164.
Patient with diabetes and a suspec ted foot infectionCleanse, debride, and probe the woundAssess neurologic and vascular status of footAssess for purulence or signs of inammationConsider plain radiography or magnetic resonance imagingObtain appropriate specimens for cultureObtain other appropriate laboratory testsAssess any medical comorbiditiesDetermine if surgical consultation is neededAssess patients psychosocial situation
Classify the wound (if needed)
Mild/moderate Severe
Assess the need for inpatient treatmentReview any available microbiologic dataSelect initial antibiotic regimen (consider
oral, relatively narrow spectrum)Select appropriate wound care (dressing,
off-loading)If treated as outpatient, set up return
visit, consultations
Hospitalize patientAttend to patients uid, electrolyte,
metabolic needsObtain blood culturesSelect empiric, broad-spectrum
parenteral antibiotic regimen (considermultidrug-resistant organisms)
Arrange for urgent surgery, if needed
If patient not hospitalized, reassess in 2 to 4 days,or earlier if condition worsens substantially
Reassess clinically at least once daily;check inammatory markers as needed
Assess clinical signs/symptoms of infection
Consider de-escalating antibioticregimen (narrower spectrum,less toxic, less expensive)
Reassess patient and woundweekly until infection resolves
If infection fails to resolveor relapses, consider deepabscess, osteomyelitis, orresistant pathogen
Review culture andsensitivity results
Assess patients adherenceto treatment regimen
Reassess wound care,need to hospitalize
Consider further imagingReculture wound
Switch to appropriate oralantibiotic regimen
Follow up as outpatient
Dene extent of tissue involved(magnetic resonance imaging,surgical exploration)
Review culture and sensitivityresults; cover all isolates
Consider broadening antibioticspectrum
Reassess need for surgery,including revascularization oramputation
Assess clinical signs/symptoms of infection
Improving Not improving/worsening Improving Not improving/worsening
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PreventionAll patients with diabetes should undergo asystematic foot examination at least once a year, and more f requently if risk factors fordiabetic foot ulcers exist (Table 5) .37 Appro-priate preventive measures include patienteducation about proper foot care, glycemicand blood pressure control, smoking cessa-tion, use of prescription footwear, intensivepodiatric care, and evaluation for surgicalinterventions as indicated.Data Sources: A PubMed search was completed inClinical Queries using the terms diabetic, foot, and infec-tions. The search included meta-analyses, randomizedcontrolled trials, clinical trials, reviews, expert opinions,and guidelines. We also searched the Cochrane database,Clinical Evidence, and Essential Evidence Plus. Searchdates: February 1, 2012, to November 30, 2012.
The AuthorsFASSIL W. GEMECHU, MD, is a staff physician and assis-tant professor in the Department of Family Medicine atMetroHealth Medical Center in Cleveland, Ohio.
FNU SEEMANT, MD, is a fellow in primary care sportsmedicine in the University Orthopedic Center at the StateUniversity of New York at Buffalo. At the time this articlewas written, he was a fellow in the Department of FamilyMedicine at MetroHealth Medical Center.
CATHERINE A. CURLEY, MD, is division director in the Divi-sion of Hospital Medicine and an assistant professor ofmedicine at MetroHealth Medical Center.
Address correspondence to Fassil W. Gemechu,MD, MetroHealth Medical Center, 4229 Pearl Rd.,
Cleveland, OH 44109 (e-mail: [email protected]). Reprints are not available from the authors.
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Table 5. Risk Classication System of the ADA Task Force of the Foot Care Interest Group
Riskcategory Denition Treatment recommendations Suggested follow-up
0 No loss of protective sensation,no peripheral arterial disease,no deformity
Consider patient education on foot care,including information on appropriate footwear
Annually (by primary carephysician and/or specialist)
1 Loss of protective sensationwith or without deformity Consider prophylactic surgery if deformity cannotbe safely accommodated in shoesContinue patient educationConsider the use of prescriptive or
accommodative footwear
Every 3 to 6 months (byprimary care physician orspecialist)
2 Peripheral arterial disease withor without loss of protectivesensation
Consider the use of accommodative footwearConsider a vascular consultation for combined
follow-up
Every 2 to 3 months(by specialist)
3 History of ulcer or amputation Consider patient education on foot careConsider vascular consultation for combined
follow-up if peripheral arterial disease is present
Every 1 to 2 months(by specialist)
ADA = American Diabetes Association.
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37. Boulton AJ, Armstrong DG, Albert SF, et al. Compre-hensive foot examination and risk assessment: a reportof the task force of the Foot Care Interest Group of theAmerican Diabetes Association, with endorsement bythe American Association of Clinical Endocrinologists.Diabetes Care . 2008;31(8):1679-1685.