Diabetic Foot Infections and the Hospitalist

Diabetic Foot Infections and the Diabetic Foot Infections and the HospitalistHospitalist

Jim Pile, MD, FACPJim Pile, MD, FACP

Divisions of Hospital Medicine and Divisions of Hospital Medicine and Infectious DiseasesInfectious Diseases

CWRU/MetroHealth Medical CenterCWRU/MetroHealth Medical Center

The ProblemThe Problem

Diabetic foot infections are common, expensive Diabetic foot infections are common, expensive and probably increasing in frequencyand probably increasing in frequency

The most frequent reason for hospitalization in The most frequent reason for hospitalization in diabetic patientsdiabetic patients

The most common reason for amputationsThe most common reason for amputations

Current treatment often fails to conform to Current treatment often fails to conform to available evidence/guidelinesavailable evidence/guidelines

Scope of Diabetic Foot InfectionsScope of Diabetic Foot Infections

CellulitisCellulitis

ParonychiaParonychia

AbscessAbscess

MyositisMyositis

Infectious tendonitisInfectious tendonitis

Septic arthritisSeptic arthritis

Necrotizing fasciitisNecrotizing fasciitis

OsteomyelitisOsteomyelitis

ULCERSULCERS

Risk Factors for Diabetic Foot Risk Factors for Diabetic Foot Ulceration and InfectionUlceration and Infection

Sensory neuropathySensory neuropathy

Motor neuropathyMotor neuropathy

Autonomic neuropathyAutonomic neuropathy

Neuro-osteoarthropathic Neuro-osteoarthropathic deformities (eg Charcot)deformities (eg Charcot)

Peripheral vascular Peripheral vascular diseasedisease

HyperglycemiaHyperglycemia

Host factorsHost factors

Patient non-adherencePatient non-adherence

Sub-optimal care by Sub-optimal care by health care systemhealth care system

Audience Response QuestionAudience Response Question

Treatment of cellulitis in the patient with Treatment of cellulitis in the patient with longstanding diabetes should include coverage longstanding diabetes should include coverage of:of:

A. Gram positive organismsA. Gram positive organisms

B. Gram positive and negative organismsB. Gram positive and negative organisms

C. Gram positives and anaerobesC. Gram positives and anaerobes

D. All of the above D. All of the above

Microbiology of Diabetic Foot InfectionsMicrobiology of Diabetic Foot Infections

Gram positive organisms predominate, Gram positive organisms predominate, especially in acute woundsespecially in acute wounds

--Staph aureus--Staph aureus

--B-hemolytic strep (especially groups A and B)--B-hemolytic strep (especially groups A and B)

Chronic wounds and/or recent antibiotics:Chronic wounds and/or recent antibiotics:

--Enterobacteriaceae (and gram positives)--Enterobacteriaceae (and gram positives)

Chronic, heavily treated infections:Chronic, heavily treated infections:--Coag neg Staph, Pseudomonas, anaerobes (+ above)--Coag neg Staph, Pseudomonas, anaerobes (+ above)

Microbiology of DFIsMicrobiology of DFIs

Polymicrobial wounds typically demonstrate 3-5 Polymicrobial wounds typically demonstrate 3-5 pathogens on culturepathogens on culture

Significance of all of these often unclear, Significance of all of these often unclear, howeverhowever

Limb (and life) threatening infections should be Limb (and life) threatening infections should be assumed to be polymicrobial until proven assumed to be polymicrobial until proven otherwiseotherwise

Wound CultureWound Culture

Neglected or done incorrectly much of timeNeglected or done incorrectly much of time

Don’t Don’t culture uninfected ulcers!culture uninfected ulcers!

Failure to debride wound before culture a Failure to debride wound before culture a common mistakecommon mistake

Tissue from debrided ulcer base provides Tissue from debrided ulcer base provides optimal material for cultureoptimal material for culture

But swab from But swab from debrideddebrided ulcer also acceptable ulcer also acceptable

Staging Severity of InfectionStaging Severity of Infection

Staging classification adopted by International Consensus Staging classification adopted by International Consensus on Diabetic Foot and IDSA utilizes PEDIS acronym:on Diabetic Foot and IDSA utilizes PEDIS acronym:

--PP: perfusion: perfusion

--EE: extent/size: extent/size

--DD: depth/tissue loss: depth/tissue loss

--II: infection: infection

--SS: sensation: sensation

--Lipsky B, Clin Infect Dis 2004;39:885Lipsky B, Clin Infect Dis 2004;39:885

DFI StagingDFI Staging

Uninfected (PEDIS 1)Uninfected (PEDIS 1)

Mild infection (PEDIS 2)Mild infection (PEDIS 2)

--Superficial, cellulitis < 2 cmSuperficial, cellulitis < 2 cm

Moderate infection (PEDIS 3)Moderate infection (PEDIS 3)

--Cellulitis > 2 cm, lymphangitis, abscess, gangreneCellulitis > 2 cm, lymphangitis, abscess, gangrene

Severe infection (PEDIS 4)Severe infection (PEDIS 4)

--Systemic involvement (fever, hypotension, leukocytosis, Systemic involvement (fever, hypotension, leukocytosis,

severe hypoglycemia, renal failure, etc.)severe hypoglycemia, renal failure, etc.)

Admission CriteriaAdmission Criteria

Essentially all patients Essentially all patients with severe infection, and with severe infection, and some with moderate, some with moderate, require hospitalizationrequire hospitalization

Most patients with mild Most patients with mild infection may be treated infection may be treated as outpatientsas outpatients

Reasons for admissionReasons for admission::

-Systemic toxicity-Systemic toxicity

-Severe metabolic -Severe metabolic disturbancesdisturbances

-Rapid progression-Rapid progression

-Critical ischemia-Critical ischemia

-Unable to care for self-Unable to care for self

-Need for urgent diagnostic or -Need for urgent diagnostic or therapeutic interventionstherapeutic interventions


A 44 year old woman with A 44 year old woman with poorly controlled T2DM poorly controlled T2DM and a plantar ulcer to the R and a plantar ulcer to the R great toe of > 1 month great toe of > 1 month duration presents with duration presents with several days of several days of progressive pain, erythema progressive pain, erythema and swelling of the foot. and swelling of the foot. Tc is 38.4Tc is 38.4° C, her WBC is ° C, her WBC is 14K and her BS is > 400.14K and her BS is > 400.


Which of the following antibiotic regimens is Which of the following antibiotic regimens is MOST appropriate?MOST appropriate?

A. MeropenemA. Meropenem

B. Ciprofloxacin + metronidazoleB. Ciprofloxacin + metronidazole

C. Piperacillin-tazobactam + vancomycinC. Piperacillin-tazobactam + vancomycin

D. Clindamycin + levofloxacinD. Clindamycin + levofloxacin

Antibiotic TherapyAntibiotic Therapy

Does the patient need antibiotics?Does the patient need antibiotics?

Choice of agent will be dictated by severity of Choice of agent will be dictated by severity of infection as well as chronicityinfection as well as chronicity

Difficult to make definitive recommendations Difficult to make definitive recommendations based on available databased on available data

Mild Diabetic Foot InfectionsMild Diabetic Foot Infections

DicloxacillinDicloxacillin

ClindamycinClindamycin

CephalexinCephalexin

Trimethoprim-Trimethoprim-SulfamethoxazoleSulfamethoxazole

LevofloxacinLevofloxacin

How does progressive How does progressive emergence of CA-MRSA emergence of CA-MRSA affect these affect these recommendations?recommendations?

Ideal regimen will reliably Ideal regimen will reliably cover CA-MRSA and B-cover CA-MRSA and B-hemolytic Strephemolytic Strep

Moderate DFIModerate DFI

Trimethoprim-Trimethoprim-sulfamethoxazolesulfamethoxazole

Amox/clavulanateAmox/clavulanate

LevofloxacinLevofloxacin

CefoxitinCefoxitin

CeftriaxoneCeftriaxone

Amp/sulbactamAmp/sulbactam

Linezolid (+/- aztreonam)Linezolid (+/- aztreonam)

Daptomycin (+/- Daptomycin (+/- aztreonam)aztreonam)

ErtapenemErtapenem

Cefuroxime +/- Cefuroxime +/- metronidazolemetronidazole

Piperacillin/tazobactamPiperacillin/tazobactam

FQ + clindamycinFQ + clindamycin

Severe DFIsSevere DFIs

Piperacillin-tazobactamPiperacillin-tazobactam

Levofloxacin Levofloxacin or or ciprofloxacin + clindamycinciprofloxacin + clindamycin

Imipenem-cilastatin Imipenem-cilastatin

Vancomycin + ceftazidime (+/- metronidazole)Vancomycin + ceftazidime (+/- metronidazole)

Surgical IndicationsSurgical Indications

Urgent:Urgent:

-Gas gangrene-Gas gangrene

-Necrotizing fasciitis-Necrotizing fasciitis

-Compartment syndrome-Compartment syndrome

-Critical ischemia-Critical ischemia

Other indications:Other indications:

-Abscess-Abscess

-Progressive infection -Progressive infection despite antibioticsdespite antibiotics

-Unexplained foot pain-Unexplained foot pain

-Need for ulcer -Need for ulcer debridementdebridement

Goals of SurgeryGoals of Surgery

Drainage of pusDrainage of pus

Correction of severe ischemiaCorrection of severe ischemia

Control of infectionControl of infection

Salvage of functional footSalvage of functional foot

Surgical expertise varies locallySurgical expertise varies locally

Important Adjuncts to Ulcer Important Adjuncts to Ulcer HealingHealing

Off-loadingOff-loading-Mechanical stress on ulcerated area MUST be prevented-Mechanical stress on ulcerated area MUST be prevented

-Bedrest, crutches, surgical/half shoes, removable cast walker, etc. -Bedrest, crutches, surgical/half shoes, removable cast walker, etc.

DebridementDebridement-Sharp debridement generally preferable-Sharp debridement generally preferable

Appropriate dressingAppropriate dressing-Moist wound environment promotes epithelialization-Moist wound environment promotes epithelialization

-Many commercial products available, none clearly superior-Many commercial products available, none clearly superior

Emerging TherapyEmerging Therapy

Hyperbaric oxygenHyperbaric oxygen

Negative pressure dressingsNegative pressure dressings

G-CSFG-CSF

Maggot therapyMaggot therapy

None of above should be a substitute for None of above should be a substitute for appropriate antibiotics and surgical therapyappropriate antibiotics and surgical therapy

Discharge CriteriaDischarge Criteria

No evidence-based No evidence-based criteria existcriteria exist

Extrapolating from Extrapolating from community-acquired community-acquired pneumonia literature, as pneumonia literature, as a minimum the following a minimum the following should be met:should be met:

T T ≤ 37.8 C≤ 37.8 C

Blood pressure > 90Blood pressure > 90

Pulse < 100Pulse < 100

Mental status at baselineMental status at baseline

-Mandell LA, IDSA/ATS Consensus -Mandell LA, IDSA/ATS Consensus

Guidelines on the Management of CAP Guidelines on the Management of CAP in Adults. CID 2007;44:S27-72.in Adults. CID 2007;44:S27-72.

Discharge CriteriaDischarge Criteria

Adequate glycemic control should be presentAdequate glycemic control should be present

Any immediately necessary surgery should be Any immediately necessary surgery should be accomplishedaccomplished

Clear wound care and off-loading plans should be Clear wound care and off-loading plans should be outlined and clear to patientoutlined and clear to patient

Definitive antibiotic regimen selectedDefinitive antibiotic regimen selected

Site of care, follow-up appointments and Site of care, follow-up appointments and communication with PCPcommunication with PCP

"Dealing with osteomyelitis is perhaps "Dealing with osteomyelitis is perhaps the most difficult and controversial the most difficult and controversial aspect in the management of diabetic aspect in the management of diabetic foot infections."foot infections."

-Lipsky BA. Diagnosis and Treatment of Diabetic Foot -Lipsky BA. Diagnosis and Treatment of Diabetic Foot Infections. Clin Infect Dis 2004;39:885-910Infections. Clin Infect Dis 2004;39:885-910

Suspect Osteomyelitis When . . . .Suspect Osteomyelitis When . . . .

An ulcer is chronic or An ulcer is chronic or overlies boneoverlies bone

An ulcer fails to heal after An ulcer fails to heal after ≥ 6 weeks of appropriate ≥ 6 weeks of appropriate treatmenttreatment

A "sausage toe" is presentA "sausage toe" is present

A swollen foot is present A swollen foot is present with a history of foot with a history of foot ulcerationulceration

An ulcer is accompanied by An ulcer is accompanied by otherwise unexplained otherwise unexplained elevated ESR/CRPelevated ESR/CRP

Bone is visible or can be Bone is visible or can be probed in an ulcer baseprobed in an ulcer base

Any ulcer that is deep or Any ulcer that is deep or extensiveextensive

Ulcer area is > 2 cmUlcer area is > 2 cm²²

-Lipsky B, CID 2004;39:885; Butalia S, -Lipsky B, CID 2004;39:885; Butalia S, JAMA 2008;299:806JAMA 2008;299:806


The single BEST test for the diagnosis of The single BEST test for the diagnosis of osteomyelitis in the diabetic foot is:osteomyelitis in the diabetic foot is:

A. WBC-tagged nuclear scanA. WBC-tagged nuclear scan

B. Positive probe-to-bone testB. Positive probe-to-bone test

C. MRIC. MRI

D. FDG-PETD. FDG-PET

Osteomyelitis of the Foot: Diagnostic Osteomyelitis of the Foot: Diagnostic ChallengesChallenges

Distinction between soft tissue and OM (or Distinction between soft tissue and OM (or uninfected ulcer and OM) frequently unclearuninfected ulcer and OM) frequently unclear

Changes on plain XR delayed and inconsistentChanges on plain XR delayed and inconsistent

Lab values don't provide resolution between OM Lab values don't provide resolution between OM and STIand STI

Neuro-osteoarthropathy (Charcot) may mimic OMNeuro-osteoarthropathy (Charcot) may mimic OM

Advanced imaging is expensiveAdvanced imaging is expensive

Plain FilmsPlain Films

Simple and cheapSimple and cheap

Radiographic changes lag Radiographic changes lag clinical pathologyclinical pathology

Recent review found Recent review found sensitivity/specificity sensitivity/specificity 61%/72%61%/72%

Probably underutilizedProbably underutilized

--Learch T, Advanced Imaging of the Learch T, Advanced Imaging of the

Diabetic Foot and its Complications. Diabetic Foot and its Complications. www.gentili.net/diabeticfoot.www.gentili.net/diabeticfoot.

Nuclear Medicine ImagingNuclear Medicine Imaging

Sensitivity is highSensitivity is high

Relatively expensiveRelatively expensive

Time consumingTime consuming

Specificity is problematicSpecificity is problematic

WBC-tagged scans may WBC-tagged scans may be helpful in be helpful in distinguishing Charcot distinguishing Charcot arthropathy from OMarthropathy from OM

--Lipman B, Clin Nucl Med 1998,23:77Lipman B, Clin Nucl Med 1998,23:77

MRIMRI

Focal decrease in marrow signal on T1-weighted Focal decrease in marrow signal on T1-weighted and increase on fat-suppressed T2-weighted and increase on fat-suppressed T2-weighted images suggests diagnosis of osteomyelitisimages suggests diagnosis of osteomyelitis

Sensitivity highSensitivity high

Much more specific than nuclear studiesMuch more specific than nuclear studies

Expense suggests MRI may be over-utilized in Expense suggests MRI may be over-utilized in this settingthis setting

MRI vs. Other Imaging ModalitiesMRI vs. Other Imaging Modalities

Recent meta-analysis found that at sensitivity of Recent meta-analysis found that at sensitivity of 90%, specificity of MRI for foot osteomyelitis was 90%, specificity of MRI for foot osteomyelitis was 83%83%

MRI markedly better than nuclear studies or plain MRI markedly better than nuclear studies or plain filmsfilms

DOR 150 vs. 3.6 for MRI vs. bone scanDOR 150 vs. 3.6 for MRI vs. bone scan

DOR 82 vs. 3.3 for MRI vs. plain filmsDOR 82 vs. 3.3 for MRI vs. plain films

- - Kapoor, A. et al. Arch Intern Med 2007;167:125-132.

Kapoor, A. et al. Arch Intern Med 2007;167:125-132.

Probe-to-Bone TestProbe-to-Bone Test

Bedside test touted as low-Bedside test touted as low-tech means of diagnosistech means of diagnosis

Positive predictive value Positive predictive value reported as 89%reported as 89%

Recent studies suggest Recent studies suggest caution with generalizing caution with generalizing these resultsthese results-Grayson M, JAMA 1995;273:721; Shone -Grayson M, JAMA 1995;273:721; Shone A, Diab Care 2006;29:945; Lavery L, Diab A, Diab Care 2006;29:945; Lavery L, Diab Care 2007;30:270Care 2007;30:270

Probe-to-Bone Characteristics Depend Probe-to-Bone Characteristics Depend on Prevalence of Osteomyelitison Prevalence of Osteomyelitis

SensSens SpecSpec PPVPPV NPVNPV PrevPrev

GraysonGrayson 66%66% 85%85% 89%89% 56%56% 66%66%

ShoneShone 38%38% 91%91% 53%53% 85%85% 20%20%

LaveryLavery 87%87% 91%91% 57%57% 98%98% 12%12%

Bone BiopsyBone Biopsy

76 patients with 81 episodes of DFO confirmed by 76 patients with 81 episodes of DFO confirmed by bone biopsybone biopsy

69 cases had ulcer swab cultures as well69 cases had ulcer swab cultures as well

Bone biopsy isolates: 77% gram +, 18% gram Bone biopsy isolates: 77% gram +, 18% gram negative, 5% anaerobesnegative, 5% anaerobes

Bone/ulcer cxs concordant in 17%Bone/ulcer cxs concordant in 17%

70% of ulcer cxs did not grow bone pathogen(s)70% of ulcer cxs did not grow bone pathogen(s)

--Senneville E, Clin Infect Dis 2006;42:57Senneville E, Clin Infect Dis 2006;42:57

IDSA Guidelines Approach to IDSA Guidelines Approach to Suspected Diabetic Foot OMSuspected Diabetic Foot OM

1. Begin with plain films of foot1. Begin with plain films of foot

-If c/w osteomyelitis, treat as such-If c/w osteomyelitis, treat as such

2. If plain films 2. If plain films not not suggestive of osteomyelitissuggestive of osteomyelitis

A. "Conservative approach":A. "Conservative approach":

--Treat soft tissue infx for 2-4 weeks, then --Treat soft tissue infx for 2-4 weeks, then repeat XRrepeat XR

B. "Aggressive approach":B. "Aggressive approach":

--Obtain MRI (or nuclear scan)--Obtain MRI (or nuclear scan)

Osteomyelitis: Medical vs. Surgical Osteomyelitis: Medical vs. Surgical TreatmentTreatment

Traditional thinking mandates resection of infected Traditional thinking mandates resection of infected bonebone

Even limited amputations may adversely affect foot Even limited amputations may adversely affect foot mechanics, setting up vicious cyclemechanics, setting up vicious cycle

Slowly mounting evidence that many cases of diabetic Slowly mounting evidence that many cases of diabetic foot OM respond to antibiotics alonefoot OM respond to antibiotics alone

Recent study of 147 pts found 77% treated medically, Recent study of 147 pts found 77% treated medically, with good result in 82% of thesewith good result in 82% of these

-Game FL, Diabetologia DOI 10.1007/s00125-008-0976-1-Game FL, Diabetologia DOI 10.1007/s00125-008-0976-1


A 53 y.o. diabetic patient is admitted to your A 53 y.o. diabetic patient is admitted to your service with an erythematous, swollen right 3service with an erythematous, swollen right 3rdrd toe and forefoot cellulitis. The toe infection toe and forefoot cellulitis. The toe infection appears to have been prompted by a plantar ulcer appears to have been prompted by a plantar ulcer of several weeks duration. An MRI strongly of several weeks duration. An MRI strongly suggests osteomyelitis of the proximal and distal suggests osteomyelitis of the proximal and distal phalanges of the 3phalanges of the 3rdrd toe, and she undergoes ray toe, and she undergoes ray resection. How long should she be treated with resection. How long should she be treated with antibiotics post-operatively?antibiotics post-operatively?

ARS (continued)ARS (continued)

A. She doesn't require additional antibiotics, the A. She doesn't require additional antibiotics, the non-viable bone has been removednon-viable bone has been removed

B. 7-10 daysB. 7-10 days

C. 2-4 weeksC. 2-4 weeks

D. 4-6 weeksD. 4-6 weeks

Duration of Treatment for Diabetic Duration of Treatment for Diabetic Foot InfectionsFoot Infections

SummarySummary

The microbiology of DFIs is at least somewhat The microbiology of DFIs is at least somewhat predictable, based on chronicity and antibiotic predictable, based on chronicity and antibiotic exposureexposure

Cultures should be obtained from the base of a Cultures should be obtained from the base of a debrideddebrided ulcer ulcer

Many cases of diabetic foot osteomyelitis can be Many cases of diabetic foot osteomyelitis can be treated based on plain films alonetreated based on plain films alone

All tests are fallible, but MRI offers the best All tests are fallible, but MRI offers the best combination of sensitivity and specificitycombination of sensitivity and specificity

Diabetic Foot Infections and the Hospitalist

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