Guideline for Diabetic Foot - 2004

7/31/2019 Guideline for Diabetic Foot - 2004

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Guidelines for Diabetic Foot Infections CID 2004:39 (1 October) 885

I D S A G U I D E L I N E S

Diagnosis and Treatment of Diabetic Foot InfectionsBenjamin A. Lipsky,1,a Anthony R. Berendt,2,a H. Gunner Deery,3 John M. Embil,4 Warren S. Joseph, 5

Adolf W. Karchmer,6 Jack L. LeFrock,7 Daniel P. Lew, 8 Jon T. Mader, 9,b Carl Norden,10 and James S. Tan 111Medical Service, Veterans Affairs Puget Sound Health Care System, and Division of General Internal Medicine, Department of Medicine,University of Washington School of Medicine, Seattle, Washington;2Bone Infection Unit, Nufeld Orthopaedic Centre, Oxford, United Kingdom;3Northern Michigan Infectious Diseases, Petoskey, Michigan;4Section of Infectious Diseases, Department of Medicine, University of Manitoba,Winnipeg, Manitoba;5Section of Podiatry, Department of Primary Care, Veterans Affairs Medical Center, Coatesville, Pennsylvania;6Divisionof Infectious Diseases, Department of Medicine, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts;7Dimensional Dosing Systems, Sarasota, Florida;8Department of Medicine, Service of Infectious Diseases, University of Geneva Hospitals,Geneva, Switzerland;9Department of Internal Medicine, The Marine Biomedical Institute, and Department of Orthopaedics and Rehabilitation,University of Texas Medical Branch, Galveston, Texas;10 Department of Medicine, New Jersey School of Medicine and Dentistry, and CooperHospital, Camden, New Jersey; and11 Department of Internal Medicine, Summa Health System, and Northeastern Ohio UniversitiesCollege of Medicine, Akron, Ohio

EXECUTIVE SUMMARY

1. Foot infections in patients with diabetes causesubstantial morbidity and frequent visits to health careprofessionals and may lead to amputation of a lowerextremity.

2. Diabetic foot infections require attention to local(foot) and systemic (metabolic) issues and coordinatedmanagement, preferably by a multidisciplinary foot-care team (A-II) (table 1). The team managing theseinfections should include, or have ready access to, an

infectious diseases specialist or a medicalmicrobiologist(B-II).3. The major predisposing factor to these infections

is foot ulceration, which is usually related to peripheralneuropathy. Peripheral vascular disease and various im-munological disturbances play a secondary role.

4. Aerobic gram-positive cocci (especially Staphy-lococcus aureus ) are the predominant pathogens indiabetic foot infections. Patients who have chronic

Received 2 July 2004; accepted 2 July 2004; electronically published 10September 2004.

These guidelines were developed and issued on behalf of the InfectiousDiseases Society of America.

a B.A.L. served as the chairman and A.R.B. served as the vice chairman of theInfectious Diseases Society of America Guidelines Committee on Diabetic FootInfections.

b Deceased.Reprints or correspondence: Dr. Benjamin A. Lipsky, Veterans AffairsPuget Sound

Health Care System, S-111-GIMC, 1660 S. Columbian Way, Seattle, WA 98108-9804 ([email protected]).

Clinical Infectious Diseases 2004;39:885910This article is in the public domain, and no copyright is claimed.1058-4838/2004/3907-0001

wounds or who have recently received antibiotic ther-apy may also be infected with gram-negative rods, andthose with foot ischemia or gangrene may have obligateanaerobic pathogens.

5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signsand symptoms of inammation. Laboratory (includingmicrobiological) investigations are of limited use fordiagnosing infection, except in cases of osteomyelitis(B-II).

6. Send appropriately obtained specimens for cul-

ture prior to starting empirical antibiotic therapy in allcases of infection, except perhaps those that are mildand previously untreated (B-III). Tissue specimens ob-tained by biopsy, ulcer curettage, or aspiration are pref-erable to wound swab specimens (A-I).

7. Imaging studies may help diagnose or better de-ne deep, soft-tissue purulent collections and are usu-ally needed to detect pathological ndings in bone.Plain radiography may be adequate in many cases, butMRI (in preference to isotope scanning) is more sen-sitive and specic, especially for detection of soft-tissuelesions (A-I).

8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are thespecic tissues involved, the adequacy of arterial per-fusion, and the presence of systemic toxicity or meta-bolic instability. Categorization helps determine the de-gree of risk to the patient and the limb and, thus, theurgency and venue of management.

9. Available evidence does not support treat-


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886 CID 2004:39 (1 October) Lipsky et al.

Table 1. Infectious Diseases Society of AmericaUnited States Public Health Service Grading System for ranking rec-ommendations in clinical guidelines.

Category, grade Denition

Strength of recommendationA Good evidence to support a recommendation for use; should a lways be offeredB Moderate evidence to support a recommendation for use; should generally be offeredC Poor evidence to support a recommendation; optionalD Moderate evidence to support a recommendation against use; should generally not be offeredE Good evidence to support a recommendation against use; should never be offered

Quality of evidenceI Evidence from 1 properly randomized, controlled trial

II Evidence from 1 well-designed clinical trial, without randomization; from cohort or case-controlled analytic studies (preferably from 1 1 center); from multiple time-series; or fromdramatic results from uncontrolled experiments

III Evidence from opinions of respected authorities, based on clinical experience, descriptivestudies, or reports of expert committees

ing clinically uninfected ulcers with antibiotic therapy (D-III).Antibiotic therapy is necessary for virtually all infected wounds,

but it is often insufcient without appropriate wound care.10. Select an empirical antibiotic regimen on the basis of

the severity of the infection and the likely etiologic agent(s)(B-II). Therapy aimed solely at aerobic gram-positive cocci may be sufcient for mild-to-moderate infections in patients whohave not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but isindicated for severe infections, pending culture results and an-tibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data,especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Denitive therapy should

be based on both the culture results and susceptibility data andthe clinical response to the empirical regimen (C-III).

11. There is only limited evidence with which to makeinformed choices among the various topical, oral, and paren-teral antibiotic agents. Virtually all severe and some moderateinfections require parenteral therapy, at least initially (C-III).Highly bioavailable oral antibiotics can be used in most mildand in many moderate infections, including some cases of os-teomyelitis (A-II). Topical therapy may be used for some mildsupercial infections (B-I).

12. Continue antibiotic therapy until there is evidence thatthe infection has resolved but not necessarily until a woundhas healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually sufces,but some require an additional 12 weeks; for moderate andsevere infections, usually 24 weeks is sufcient, depending onthe structures involved, the adequacy of debridement, the typeof soft-tissue wound cover, and wound vascularity (A-II); andfor osteomyelitis, generally at least 46 weeks is required, buta shorter duration is sufcient if the entire infected bone is

removed, and probably a longer duration is needed if infectedbone remains (B-II).

13. If an infection in a clinically stable patient fails to re-spond to 1 antibiotic courses, consider discontinuing all an-timicrobials and, after a few days, obtaining optimal culturespecimens (C-III).

14. Seek surgical consultation and, when needed, interven-tion for infections accompanied by a deep abscess, extensivebone or joint involvement, crepitus, substantial necrosis or gan-grene, or necrotizing fasciitis (A-II). Evaluating the limbs ar-terial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the eldshould be recruited by the foot-care team, if possible.

15. Providing optimal wound care, in addition to appro-

priate antibiotic treatment of the infection, is crucial for healing(A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufcient evidence to recommend use of a specic wound dressing or any type of wound healing agentsor products for infected foot wounds.

16. Patients with infected wounds require early and carefulfollow-up observation to ensure that the selected medical andsurgical treatment regimens have been appropriateand effective(B-III).

17. Studies have not adequately dened the role of mostadjunctive therapies for diabetic foot infections, but systematicreviews suggest that granulocyte colony-stimulating factors andsystemic hyperbaric oxygen therapy may help prevent ampu-tations (B-I). These treatments may be useful for severe infec-tions or for those that have not adequately responded to ther-apy, despite correcting for all amenable local and systemicadverse factors.

18. Spread of infection to bone (osteitis or osteomyelitis)may be difcult to distinguish from noninfectious osteoar-


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Table 2. Risk factors for foot ulceration and infection.

Risk factor Mechanism of injury or impairment

Peripheral motor neuropathy Abnormal foot anatomy and biomechanics , with clawing oftoes, high arch, and subluxed metatarsophalangeal joints,leading to excess pressure, callus formation, and ulcers

Peripheral sensory neuropathy Lack of protective sensation, leading to unattended minorinjuries caused by excess pressure or mechanical or ther-mal injury

Peripheral autonomic neuropathy Decient sweating leading to dry, cracking skinNeuro-osteoarthropathic deformities (i.e., Charcot disease)

or limited joint mobilityAbnormal anatomy and biomechanics, leading to excess

pressure, especially in the midplantar areaVascular (arterial) insufciency Impaired tissue viability, wound healing, and delivery of

neutrophilsHyperglycemia and other metabolic derangements Impaired immunological (especially neutrophil) function and

wound healing and excess collagen cross-linkingPatient disabilities Reduced vision, limited mobility, and previous amputation(s)

Maladaptive patient behaviors Inadequate adherence to precautionary measures and footinspection and hygiene procedures, poor compliance withmedical care, inappropriate activities, excessive weight-bearing, and poor footwear

Health care system failures Inadequate patient education and monitoring of glycemiccontrol and foot care

thropathy. Clinical examination and imaging tests may sufce,but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for dening the pathogenic organism(s), and fordetermining the antibiotic susceptibilities of such organisms(B-II).

19. Although this eld has matured, further research ismuch needed. The committee especially recommends that ad-

equately powered prospective studies be undertaken to eluci-date and validate systems for classifying infection, diagnosingosteomyelitis, dening optimal antibiotic regimens in varioussituations, and clarifying the role of surgery in treating oste-omyelitis (A-III).

INTRODUCTION

Purpose of the guideline. Foot infections in persons with di-abetes are a common, complex, and costly problem [14]. Inaddition to causing severe morbidities, they now account forthe largest number of diabetes-related hospital beddays [5]and are the most common proximate, nontraumatic cause of amputations [6, 7]. Diabetic foot infections require careful at-tention and coordinated management, preferably by a multi-disciplinary foot-care team (A-II) [813]. The team managingthese infections should preferably include, or have ready accessto, an infectious diseases specialist or a medical microbiologist(B-III) [1]. Optimal management of diabetic foot infectionscan potentially reduce the incidence of infection-related mor-bidities, the need for and duration of hospitalization, and theincidence of major limb amputation [14, 15]. Unfortunately,these infections are frequently inadequately managed [16]. This

may result from a lack of understanding of current diagnosticand therapeutic approaches, insufcient resources devoted tothe problem, or a lack of effective multidisciplinary collabo-ration. The primary purpose of this guideline is to help reducethe medical morbidity, psychological distress, and nancialcosts associated with diabetic foot infections.

The focus of this guideline is primarily on managing the

diabetic patient with suspected or evident foot infection, be-cause other published guidelines cover the generalmanagementof the diabetic foot and diabetic foot ulceration [1719]. Thecommittee members realize that the realities of primary carepractice and the scarcity of resources in some clinical situationswill restrict the implementation of some of the recommendedprocedures and treatments. We believe, however, that in almostall settings, high-quality care is usually no more difcult toachieve or expensive than poor care and its consequences [20,21].

This guideline should provide a framework for treating alldiabetic patients who have a suspected foot infection. Somehealth care centers will be able to implement it immediately,whereas others will need increased resources, better staff train-ing, and intensied coordination of available expertise. Use of this guideline may reduce the burdens (medical, nancial, andecological) associated with inappropriate practices, includingthose related to antibiotic prescribing, wound care, hospitali-zation decisions, diagnostic testing, surgical procedures, andadjunctive treatments. We hope it will contribute to reducingthe rates of lower extremity amputation, in line with the in-ternational St. Vincent declaration [22]. Cost savings may en-


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Table 3. Pathogens associated with various clinical foot-infection syndromes.

Foot-infection syndrome Pathogens

Cellulitis without an open skin wound b -Hemolytic streptococcus a and Staphylococcus aureus Infected ulcer and antibiotic naive b S. aureus and b -hemolytic streptococcus a

Infected ulcer that is chronic or was previously treated withantibiotic therapy c

S. aureus, b -hemolytic streptococcus, andEnterobacteriaceae

Ulcer that is macerated because of soaking c Pseudomonas aeruginosa (often in combination with otherorganisms)

Long duration nonhealing wounds with prolonged, broad-spectrum antibiotic therapy c,d

Aerobic gram-positive cocci ( S. aureus , coagulase-negativestaphylococci, and enterococci), diphtheroids, Enterobac-teriaceae, Pseudomonas species, nonfermentative gram-negative rods, and, possibly, fungi

Fetid foot: extensive necrosis or gangrene, malodorous c Mixed aerobic gram-positive cocci, including enterococci,Enterobacteriaceae, nonfermentative gram-negative rods,and obligate anaerobes

a Groups A, B, C, and G.b Often monomicrobial.c Usually polymicrobial.d Antibiotic-resistant species (e.g., methicillin-resistant S. aureus, vancomycin-resistant enterococci, or extended-spectrum b -lactamase

producing gram-negative rods) are common.

sue, although this may be offset by an increased demand forpreventive foot care, diagnostic testing (especially MRI), andvascular interventions [12].

Methodology. This guideline committee is comprised of Infectious Diseases Society of America members with experi-ence and interest in diabetic foot infections, many of whomalso have experience in writing guidelines. Committee membersare from several US states and other countries; their back-grounds represent academia, bench and clinical research, in-fectious diseases clinical practice, podiatry, and industry. Threeof the members are also members of the International WorkingGroup on the Diabetic Foot, which published its International

Consensus Guidelines on Diagnosing and Treating DiabeticFoot Infections in 2003 [23]. After an extensive literaturesearch(which included the MEDLINE database, the EBSCO database,the Cochrane Library, diabetic foot Web sites and bibliogra-phies, and hand-searching of bibliographies of published ar-ticles), committee members reviewed and discussed all availableevidence in a series of meetings and established consensusthrough discussion and debate over a period of 3 years. Threesubcommittees drafted subsections that were modied and ex-changed; these served as a basis for the nal document, whichunderwent numerous revisions that were based on both internaland external reviews. Because of the relative paucity of ran-

domized controlled trials or other high-quality evidence in thiseld, most of our recommendations are based on discussionand consensus (B-II) (table 1) [24]. Thus, we elected to offera relatively brief summary and to provide an extensive bibli-ography for those who would like to review the data themselves.

PATHOPHYSIOLOGY OF INFECTION

A diabetic foot infection is most simply dened as any infra-malleolar infection in a person with diabetes mellitus. These

include paronychia, cellulitis, myositis, abscesses, necrotizingfasciitis, septic arthritis, tendonitis, and osteomyelitis. The mostcommon and classical lesion, however, is the infected diabeticmal perforans foot ulcer. This wound results from a complex amalgam of risk factors [25, 26], which are summarized intable 2. Neuropathy plays the central role, with disturbancesof sensory, motor, and autonomic functions leading to ulcer-ation due to trauma or excessive pressure on a deformed footthat lacks protective sensation. Once the protective layer of skinis breached, underlying tissues are exposed to bacterial colo-nization. This wound may progress to become actively infected,and, by contiguous extension, the infection can involve deeper

tissues. This sequence of events can be rapid (occurring overdays or even hours), especially in an ischemic limb. Variouspoorly characterized immunologic disturbances, especially those that involve polymorphonuclear leukocytes, may affectsome diabetic patients, and these likely increase the risk andseverity of foot infections [2730].

MICROBIOLOGY

Aerobic gram-positive cocci are the predominant microorgan-isms that colonize and acutely infect breaks in the skin. S. aureus and the b -hemolytic streptococci (groups A, C, and G, but

especially group B) are the most commonly isolated pathogens[3138]. Chronic wounds develop a more complex colonizingora, including enterococci, various Enterobacteriaceae, obli-gate anaerobes, Pseudomonas aeruginosa, and, sometimes, othernonfermentative gram-negative rods [3943]. Hospitalization,surgical procedures, and, especially, prolonged or broad-spec-trum antibiotic therapy may predispose patients to colonizationand/or infection with antibiotic-resistant organisms (e.g.,MRSA or vancomycin-resistant enterococci [VRE]) [44]. Al-


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Figure 1. Algorithm 1, part 1: approach to treating a diabetic patient with a foot wound

though MRSA strains have previously been isolated mainly from hospitalized patients, community-associated cases arenow becoming common [45] and are associated with worseoutcomes in patients with diabetic foot infections [4648]. Van-comycin (or glycopeptide)intermediate S. aureus has been iso-lated in several countries. Of note, the rst 2 reported cases of vancomycin-resistant S. aureus each involved a diabetic patientwith a foot infection [49].

The impaired host defenses around necrotic soft tissue orbone may allow low-virulence colonizers, such as coagulase-

negative staphylococci and Corynebacterium species (diph-theroids), to assume a pathogenic role [43, 50]. Acute infec-tions in patients who have not recently received antimicrobialsare often monomicrobial (almost always with an aerobic gram-positive coccus), whereas chronic infections are often polym-icrobial [31, 36, 43, 51]. Cultures of specimens obtained frompatients with such mixed infections generally yield 35 isolates,including gram-positive and gram-negative aerobes and an-aerobes [14, 34, 37, 38, 40, 41, 5258]. The pathogenic role of each isolate in a polymicrobial infection is often unclear. Table


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890

T a b l e 4 .

E v a l u a t i n g t h e

d i a b e t i c p a t i e n t w h o h a s a n i n f e c t e d f o o t .

L e v e l o f e v a l u a t i o n , b y a r e a ( s )

t o b e a s s e s s e d

R e l e v a n t p r o b l e m s a n d o b s e r v a t i o n s

I n v e s t i g a t i o n s

P a t i e n t

S y s t e m i c r e s p o n s e t o

i n f e c t i o n

F e v e r , c h i l l s , s w e a t s

, v o m i t i n g , h

y p o t e n s i o n , a

n d

t a c h y c a r d i a

H i s t o r y a n d p h y s i c a l e x a m i n a t i o n

M e t a b o l i c s t a t e

V o l u m e d e p l e t i o n , a z o t e m i a

, h y p e r g l y c e m i a

,

t a c h y p n e a h y p e r o s m o l a l i t y

, a c i d o s i s

S e r u m c h e m i s t r y a n a l y s e s a n d h e m a t o l o g i c a l t e s t i n g

P s y c h o l o g i c a l / c o g n i t i v e s t a t e

D e l i r i u m , d

e m e n t i a

, d e p r e s s i o n , i m p a i r e d c o g n i t i o n ,

a n d s t u p o r

A s s e s s m e n t o f m e n t a l a n d p s y c h o l o g i c a l s t a t u s

S o c i a l s i t u a t i o n

S e l f n e g l e c t , p o t e n t i a l n o n c o m p l i a n c e , a n d l a c k o f

h o m e s u p p o r t

I n t e r v i e w s w i t h f a m i l y

, f r i e n d s , a n d h e a l t h c a r e

p r o f e s s i o n a l s

L i m b o r f o o t

B i o m e c h a n i c s

D e f o r m i t i e s , i

n c l u d i n g C h a r c o t a r t h r o p a t h y ,

c l a w / h a m m e r t o e s , a

n d c a l l o s i t i e s

C l i n i c a l f o o t e x a m i n a t i o n a n d r a d i o g r a p h y ( 2 i m a g e s )

V a s c u l a r s t a t u s

A r t e r i a l a

I s c h e m i a

, n e c r o s i s , o r g a n g r e n e

F o o t p u l s e s , b

l o o d p r e s s u r e s ( A B I ) , T c p O

2 , d

u p l e x

u l t r a s o n o g r a p h y , a n d a n g i o g r a m s

V e n o u s

E d e m a , s t a s i s

, o r t h r o m b o s i s

S k i n a n d s o f t - t i s s u e e x a m i n a t i o n a n d d u p l e x

u l t r a s o n o g r a p h y

N e u r o p a t h y

L o s s o f p r o t e c t i v e s e n s a t i o n b

L i g h t t o u c h , m o n o l a m e n t p r e s s u r e , o

r v i b r a t i o n

p e r c e p t i o n

W o u n d

S i z e a n d d e p t h ( t i s s u e s

i n v o l v e d )

N e c r o s i s , g a n g r e n e , f o r

e i g n b o d y

, a n d i n v o l v e m e n t

o f m u s c l e , t e n d o n , b

o n e , o r j o i n t

I n s p e c t , d e b r i d e ,

c

a n d p r o b e d t h e w o u n d ; a n d r a d i o -

g r a p h y ( 2 i m a g e s )

P r e s e n c e , e

x t e n t , a n d

c a u s e

o f i n f e c t i o n

P u r u l e n c e , w a r m t h

, t e n d e r n e s s , p a i n

, i n d u r a t i o n ,

c e l l u l i t i s

, b u l l a e , c r e p i t u s , a b s c e s s , f a s c i i t i s

, a n d

o s t e o m y e l i t i s

G r a m s t a i n i n g a n d c u l t u r e , e

u l t r a s o n o g r a p h y o r C T f o r

d e t e c t i o n o f d e e p a b s c e s s e s , a n d r a d i o g r a p h y ( 2

i m a g e s ) a n d / o r M R I f o r d e t e c t i o n o f o s t e o m y e l i t i s

f


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Table 5. Collection of soft-tissue specimens from an infected diabetic foot for culture.

When7 Culturing clinically uninfected lesions is unnecessary, unless done as part of an infection-control surveillance protocol (C-III).7 Cultures of infected wounds are valuable for directing antibiotic choices, but may be unnecessary in cases of acute mild

infection in an antibiotic-naive patient (B-III).7

Blood cultures should be performed for a patient with a severe infection, especially if the patient is systemically ill (C-III).How7 Cleanse and debride the lesion before obtaining specimens for culture.7 In cases involving an open wound, obtain tissue specimens from the debrided base (whenever possible) by means of curet-

tage (scraping with a sterile dermal curette or scalpel blade) or biopsy (bedside or operative) (A-I).7 Avoid swabbing undebrided ulcers or wound drainage. If swabbing the debrided wound base is the only available culture

option, use a swab designed for culturing aerobic and anaerobic organisms and rapidly transport it to the laboratory (B-I).7 Needle aspiration may be useful for obtaining purulent collections or, perhaps, a specimen from an area of cellulitis.7 Clearly identify samples (specimen type and anatomic location), and promptly send them to the laboratory in an appropriate

sterile container or transport media for aerobic and anaerobic culture.

3 lists common clinical infection syndromes and the pathogensmost likely isolated in conjunction with them.

EVALUATING THE PATIENT, THE WOUND,AND THE INFECTION

Diabetic patients may develop many types of foot wounds, any of which can become infected. Infection should be diagnosedclinically on the basis of the presence of purulent secretions(pus) or at least 2 of the cardinal manifestations of inam-mation (redness, warmth, swelling or induration, and pain ortenderness); not all ulcers are infected (gure 1) (B-II) [23].Curing an infection often contributes to, but is not dened by,healing of an ulcer. Management of diabetic foot infectionsinvolves evaluating and determining the severity of infectionas the basis for selecting the appropriate approach to treatment[15, 23, 40] (B-II). The issue of osteomyelitis is particularly complex and problematic and is thus dealt with separately.

Evaluation of the infection should occur at 3 levels, as out-lined in tables 4 and 5 (B-III): the patient as a whole, theaffected limb or foot, and the infected wound. The goal is todetermine the clinical extent (table 4) and the microbialetiology (table 5) of the infection, the biology or pathogenesis of thewound, any contribution of altered foot biomechanics to thecause of the wound (and, thus, its ability to heal), any contri-bution of vascular (especially arterial) disease, and the presenceof any systemic consequences of infection. Clinicians lackingthe skills or experience to conduct any of these assessmentsshould seek appropriate consultation.

DETERMINING THE SEVERITY OF INFECTION

The results of the evaluations described in table 4 can be usedto determine the overall severity of the infection and to for-mulate a management plan (gure 2) (B-II). Unfortunately, thelack of consensus on wound denitions and infection classi-cation systems hampers comparison of published studies. The

Wagner system [15, 40, 98, 99] has been widely used for 25 years but was developed for the dysvascular foot, is skewedtoward severe disease, and contains all infections within a singlegrade [100105]. Consensus is developing that the key issuesin classifying a diabetic foot wound are its depth (in particular,which tissues are involved) and whether the wound is com-plicated by either ischemia or infection [23, 101, 106108] (B-

II). The International Consensus on the Diabetic Foot recently published a preliminary progress report on a diabetic foot ulcerclassication system for research purposes [23]. The key ele-ments are summarized by the acronym PEDIS (perfusion, ex-tent/size, depth/tissue loss, infection, and sensation). Theinfection category includes grades 1 (no infection), 2 (involve-ment of skin and subcutaneous tissue only), 3 (extensive cel-lulitis or deeper infection), and 4 (presence of a systemic in-ammatory response syndrome). Because this research-basedsystem is designed to be applicable to all ulcers, it includes acategory of grade 1 for uninfected lesions; grades24 are similarto those we describe in table 6.

For infected wounds (gure 2), the most important initialtask is to recognize patients who require immediate hospital-ization, parenteral and broad-spectrum empirical antibiotictherapy, and urgent consideration of diagnostic testing andsurgical consultation. We have dened these potentially life-threatening infections as severe. Infections dened as mildmust be distinguished from clinically uninfected lesions but areotherwise relatively easy to recognize. Dening infections asmoderate poses the greatest difculty, because this termcovers a broad spectrum of wounds, some of which can bequite complicated and even limb threatening. Other classi-

cation schemes have used the terms uncomplicated andcomplicated synonymously with mild and moderate, but wewish to avoid confusion with the various complications thatcan beset a wound. The distinction between moderate andsevere infections has less to do with the status of the foot than


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Table 6. Clinical classication of a diabetic foot infection.

Clinical manifestations of infectionInfectionseverity

PEDISgrade a

Wound lacking purulence or any manifestations of inammation Uninfected 1Presence of 2 manifestations of inammation (purulence, or erythema, pain,

tenderness, warmth, or induration), but any cellulitis/erythema extends 2cm around the ulcer, and infection is limited to the skin or supercial subcu-

taneous tissues; no other local complications or systemic illness.

Mild 2

Infection (as above) in a patient who is systemically well and metabolically sta-ble but which has 1 of the following characteristics: cellulitis extending 1 2cm, lymphangitic streaking, spread beneath the supercial fascia, deep-tissueabscess, gangrene, and involvement of muscle, tendon, joint or bone

Moderate 3

Infection in a patient with systemic toxicity or metabolic instability (e.g., fever,chills, tachycardia, hypotension, confusion, vomiting, leukocytosis, acidosis,severe hyperglycemia, or azotemia)

Severe 4

NOTE. Denitions of terms can be found in footnotes to table 4. Foot ischemia may increase the severity of anyinfection, and the presence of critical ischemia often makes the infection severe. PEDIS, perfusion, extent/size, depth/ tissue loss, infection, and sensation.

a International Consensus on the Diabetic Foot [23].

oration or a fetid odor, has friable granulation tissue, is asso-ciated with unexpected pain or tenderness, or when an oth-erwise properly treated ulcer fails to show healingprogress[117,118]. In these unusual cases, a brief, culture-directed course of antibiotic therapy may be appropriate (C-III).

Determine the need for hospitalization. Hospitalization isthe most expensive part of treating a diabetic foot infection,and deciding on its necessity requires consideration of bothmedical and social issues. Patients with infections that are eithersevere or complicated by critical limb ischemia should generally be hospitalized (C-III) [119, 120]. Some patients with appar-ently mild infections and more patients with moderate infec-

tions may also need hospitalization; this may be for observation,urgent diagnostic testing, or because complicating factors arelikely to affect their wound care or adherence to antibiotictreatment. In the absence of these complicating features, mostpatients with mild or moderate infections can be treated asoutpatients (A-II) [84, 121].

Stabilize the patient. Attending to the general metabolicstate of the patient is essential [25, 122]. This may involverestoration of the uid and electrolyte balances; correction of hyperglycemia, hyperosmolality, acidosis, and azotemia; andtreatment of other exacerbating disorders. Critically ill patientswho require surgery should usually be stabilized before transferto the operating room, although surgery should usually not bedelayed for 1 48 h after presentation to the hospital (B-III)[123]. The improvement of glycemic control may aid in botheradicating the infection and healing the wound [124]. As theinfection improves, hyperglycemia may be easier to control.

Choose an antibiotic regimen. Selection of the antibioticregimen initially involves decisions about the route of therapy,the spectrum of microorganisms to be covered, and the specicdrugs to administer and later involves choosing the denitive

regimen and the duration of treatment. Initial therapy is usually empirical and should be based on the severity of the infectionand on any available microbiologicaldata, such as recentcultureresults or current Gram-stained smear ndings. For severe in-fections and for more-extensive, chronic moderate infections,it is safest to commence therapy with broad-spectrum agents.These should have activity against gram-positive cocci (includ-ing MRSA in locations where this pathogen is common), aswell as gram-negative and obligate anaerobic organisms (B-III).To ensure adequate and prompt tissue concentrations, therapy should be given parenterally, at least initially (C-III). Althoughsome suggest broad-spectrum empirical therapy for most in-

fections [125127], the majority of mildand many moder-ateinfections can be treated with agents with a relatively narrow spectrum, such as those covering only aerobic gram-positive cocci (A-II) [84]. Although anaerobic organisms areisolated from many severe infections [42, 128], they are infre-quent in mild-to-moderate infections [14, 84, 129], and thereis little evidence to support the need for antianaerobic therapy in most infections (B-III). For mild-to-moderate infections inpatients without gastrointestinal absorption problems and forwhom an oral agent with the appropriate spectrum is available,oral therapy is often appropriate, especially with highly bio-available agents (A-II). For mildly infected open wounds withminimal cellulitis, limited data support the use of topical an-timicrobial therapy (B-I) [130].

Antibiotics vary in how well they achieve effective concen-trations in infected diabetic foot lesions [131137]; this is as-sociated with the pharmacodynamic properties of the specicagent and, especially, the arterial supply to the foot, rather thanwith diabetes [138]. There are surprisingly few published clin-ical trials of antibiotic therapy for diabetic foot infection. Sev-eral antibiotic trials involving patients with variouscomplicated


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skin and soft-tissue infections have included some patients withdiabetic foot infections. Table 7 provides a list of publishedclinical trials that focused on therapy of diabetic foot infections,either exclusively or as an identied subset of a larger study.The lack of standardization among these trials makes the com-parison of outcomes of different regimens inappropriate. Thediffering denitions of infection severity and clinical end points

that were used in these publications highlight the need to de-velop a consensus classication system for future studies. Onthe basis of the available studies, no single drug or combinationof agents appears to be superior to others [129].

Table 8 summarizes some potential empirical antibiotic reg-imens according to the clinical severity of the infection, al-though the available data do not allow us to recommend any specic antibiotic regimen for diabetic foot infections (B-II).These suggested agents are derived from available publishedclinical trials and our collective experience and are not meantto be inclusive of all potentially reasonable regimens. Similaragents could be used, depending on various clinical, micro-biological, epidemiological, and nancial considerations. Con-sider modifying antibiotic therapy when culture and suscep-tibility results are available (C-III). Empirical choices forpatients who are not responding to antibiotic therapy shouldinclude agents that cover a different or more-extended spec-trum of organisms (B-III) (gure 3). The regimens in table 8are listed in approximate order of increasing broad-spectrumcoverage; the order does not indicate preferences by the com-mittee. Dosages of antibiotic agents should be selected accord-ing to suggestions of the US Food and Drug Administration,the drugs manufacturers, and the experience of the prescriber

and should be modied on the basis of any relevant organ(especially renal) dysfunction and other clinical factors.Determine the need for surgery. Many infections require

surgical procedures that range from drainage and excision of infected and necrotic tissues to revascularization of the lowerextremity and reconstruction of soft-tissue defects or mechan-ical misalignments [164168]. Unfortunately, surgical treat-ment of diabetic foot infections is based on even less-structuredevidence than that for antibiotic therapy [169]. Seek urgentsurgical consultation for life- or limb-threatening infections,such as those presenting with necrotizing fasciitis, gas gangrene,extensive soft-tissue loss, or evidence of compartment syn-

drome, or those in limbs with critical ischemia (A-II) [170,171]. A surgical specialist should also evaluate patients whohave unexplained persistent foot pain or tenderness and/orevidence of a deep-space infection, deep abscesses, or progres-sive infection in the face of apparently appropriate medical care(gure 3). Timely and aggressive surgical debridement, includ-ing limited resections or amputations, may reduce the need formore-extensive amputation (B-II) [172, 173]. Pus under pres-sure, especially in an ischemic foot, can cause rapid and irrep-

arable damage. For patients with less-serious infections, it may be appropriate to delay surgery to carefully observe the effec-tiveness of medical therapy or to determine the demarcationline between necrotic and viable tissue [174].

The surgeon must determine the adequacy of the blood sup-ply to the remaining viable tissues, consider common operativepitfalls (e.g., infection spreading among foot compartments, to

the deep plantar space, or along the tendon sheaths), and for-mulate a strategy for eventual soft-tissue cover (e.g., primary closure, delayed primary closure, secondary intention, or tissuetransfer) [175177]. The surgical approach should optimize thelikelihood for healing and should attempt to preserve the in-tegrity of the walking surface of the foot (B-II) [178]. In ad-dition to manual dexterity, the surgeon must have sufcientknowledge and experience to judge when and how to intervene.The surgeons training specialty is less important than his orher knowledge of the anatomy of the foot, the pathophysiology of ulceration and infection, and experience with and enthusi-asm for the eld [8]. In most instances, the surgeon shouldcontinue to observe the patient until the infection is undercontrol and the wound is healing (B-III).

In some cases, amputation is the best or only option [170,179]. Urgent amputation is usually required only when thereis extensive necrosis or life-threatening infection [180]. Electiveamputation may be considered for the patient who has recur-rent ulceration (despite maximal preventive measures), has ir-reversible loss of foot function, or would require unacceptably prolonged or intensive hospital care [181, 182]. Selection of the level of amputation must take into consideration vascular,reconstructive, and rehabilitation issues [183, 184]. Generally,

the surgeon should attempt to save as much of the limb aspossible. However, a higher-level amputation that results in amore functional residual stump (even if a prosthesis is required)may be a better choice than preserving a foot that is mechan-ically unsound, unlikely to heal, or prone to future ulceration.When all or part of a foot has dry gangrene, it may be preferable(especially for a patient for whom surgery is a poor option) tolet the necrotic portions autoamputate. It may also be best toleave adherent eschars in place, especially on the heel, untilthey soften enough to be more easily removed, provided theredoes not appear to be an underlying focus of infection [80,81].

If the infected limb appears to be ischemic, the patient shouldbe referred to a surgeon with vascular expertise [185]. In mostcases, ischemia is due to larger-vessel atherosclerosis, ratherthan to small-vessel disease [68]. Because vessels above theknee and below the ankle tend to be relatively spared, lower-extremity atherosclerosis may be amenable to angioplasty orvascular bypass [186]. Patients with noncritical ischemia (e.g.,those with an ankle to brachial artery blood pressure index of 0.50.9) can usually be successfully treated without a vascular


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Table 7. Antibiotic agents used in published clinical studies of diabetic foot infections.

Antibiotic (route)

No. oftreatedpatients Study design Patient group

Type/severity ofinfection(s) Reference

Cephalosporins

Cefoxitin (iv) 8 Prospective,noncomparative

Hospitalized Presumptive anaerobic [139]

Cefoxitin (iv) 23 RDBCT Hospitalized Moderate-to-severe [140]

Cefoxitin (iv) 60 Prospective,noncomparative

Hospitalized Failing to respond totherapy

[141]

Cefoxitin (iv) 18 RDBCT Hospitalized Mild-to-severe [142]

Cefoxitin (iv) alone 12 RCT Hospitalized Mixed [143]

Cefoxitin (iv) and amdino-cillin (iv)

13 RCT Hospitalized Mixed [143]

Ceftizoxime (iv) 20 Prospective, uncontrolled Hospitalized PVD, moderate-to-severe [144]

Ceftizoxime (iv) 23 RDBCT Hospitalized Moderate-to-severe [140]

Cephalexin (po) 29 RDBCT Outpatient Mild-to-moderate [84]

Ceftriaxone (iv) 90 Prospective, observational Hospitalized Severe limb-threatening [145]

Penicillins

Ampicillin/sulbactam (iv)(then amoxicillin/clavu-lanate [po])

53 RCT Hospitalized initially Moderate [146]

Ampicillin/sulbactam (iv) 48 RDBCT Hospitalized Limb-threatening [147]Ampici ll in/sulbactam ( iv) 74 Prospective,

noncomparativeHospitalized Moderate-to-severe [148]

Ampicillin/sulbactam (iv) 18 RDBCT Hospitalized Mild-to-severe [142]

Ampicillin/sulbactam (iv)and/or amoxicillin/clavu-lanate (po)

120 RCT Outpatient or hospitalized All types [121]

Amoxicillin/clavulanate (iv/po) 191 Observational,noncomparative

Mostly hospitalized Moderate [149]

Ticarcil lin/clavulanate ( iv) 28 RCT subgroup a Inpatient or outpatient Complicated soft-tissue [150]

Ticarci ll in /clavulanate ( iv) 17 RCT subgroup a Hospitalized Complicated soft-tissue [151]

Piperacillin/tazobactam (iv) 29 Prospective,noncomparative

Hospitalized Moderate-to-severe [152]

Piperacillin/tazobactam(iv/im)

38 Prospectivenoncomparative

Outpatient Parenteral, mostlymoderate

[153]

Piperacillin/tazobactam (iv) 34 RDBCT subgroupa

Hospitalized Severe [154]Fluoroquinolones

Ciprooxacin (po) 46 Prospective, randomizeddoses

Hospitalized PVD [155]

Ciprooxacin ( iv, then po) 43 Prospective,noncomparative

Hospitalized Soft-tissue or bone [156]

Ciprooxacin (po) andclindamycin (po)

120 Uncontrolled, quasi-prospective

Hospitalized initially, re-ceived other iv agents,and was then dis-charged home

Moderate-to-severe [157]

Ooxacin (iv, then po) 55 RCT Hospitalized initially Moderate [146]

Ooxacin (po) 420 RDBCT Outpatients Mild-to-moderatelyinfected ulcers

[130]

Levooxacin (iv or po) 26 RCT subgroup a Outpatients or inpatients Complicated soft-tissue [150]

Trovaoxacin (po) 214 Prospective,noncomparative

Soft-tissue [158]

Clinaoxacin ( iv, then po) 42 RDBCT subgroup a Hospitalized Severe [154]

Ooxacin, levooxacin, orciprooxacin (iv and/or po)

90 P rospective, obser vational Hospitali zed Severe l imb-thr eatening [145]

Carbapenems

Imipenem/cilastatin (iv) 48 RDBCT Hospitalized Limb-threatening [147]

Imipenem/cilas tatin ( iv) 94 Uncontrol led,noncomparative

Hospitalized Moderate-to-severe [159]

Imipenem/cilas tatin ( iv) 22 Randomized, open,comparative

Hospitalized Wagner grade 24wounds

[160]

Ertapenem (iv) 33 RDBCT Hospitalized Complicated soft-tissue [161]

(continued)


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Table 7. (Continued.)

Antibiotic (route)

No. oftreatedpatients Study design Patient group

Type/severity ofinfection(s) Reference

Miscellaneous agents

Aztreonam (iv) 20 Prospective subgroup a Hospitalized Acute, severe soft-tissue [162]

Clindamycin (po) 29 RDBCT Outpatient Mild-to-moderate [84]

Piperacillin/clindamycin (iv) 24 Randomized, open,

comparative

Hospitalized Wagner grade 24

wounds

[160]

Pexiganan (topical) 415 RDBCT Outpatient Mild-to-moderate infectedulcers

[130]

Linezolid (iv or po) 241 RCT Outpatient or hospitalized All types [121]

Daptomycin (iv) 50 RCT subgroup a Hospitalized Complicated skin [163]

NOTE. Trials are those in which the purpose of the study was to examine the efcacy of antibiotic therapy, and the subjects were exclusively,predominantly, or separately identiable as diabetic patients with foot infections. The clinical and microbiological outcomes were not consistentlydened or routinely provided. PVD, peripheral vascular disease; RCT, randomized controlled trial; RDBCT, randomized, double-blinded, controlledtr ial(each arm is listed separately in the table).

a Involved patients with diabetic foot infections who constituted an identied subgroup of a larger trial of skin and skin structure infections.

procedure. For more-severe vascular disease of the foot, many centers have reported successful use of femoral-distal bypass

procedures in diabetic patients [186189]. For a patient witha severely infected ischemic foot, it is usually preferable toperform any needed revascularization early after recognizingthe infection (i.e., within 12 days), rather than to delay thisprocedure in favor of prolonged (and potentially ineffective)antibiotic therapy (B-II) [123, 190]. On the other hand, carefuldebridement of necrotic infected material should not be delayedwhile awaiting revascularization. Optimal surgical managementmay require multiple, staged procedures [191].

Formulate a wound-care plan. The wound may requireadditional attention after the debridement performed duringthe initial assessment (table 4). The goal is to physically excise

dead and unhealthy tissue, thereby enabling wound healing andremoving a reservoir of potential pathogens [82, 192194]. Any experienced clinician may perform limited debridement. Thiscan usually be undertaken as a clinic or bedside procedure andwithout anesthesia, especially for a neuropathic foot. Sharpdebridement with scalpel, scissors, or tissue nippers is generally preferable to hydrotherapy or topical debriding agents, whichare less denitive and controllable and may require prolongedand repeated applications (B-III) [194, 195]. There are many wound-care products that are touted as being able to improvehealing in various ways [17, 23, 196199], but a discussion of these is beyond our scope. The infected wound should bedressed in a manner that allows daily inspection and encouragesa moist wound-healing environment (B-III). No evidence fa-vors any particular type of dressing; convenience and cost areimportant considerations. Removal of pressure from a footwound (i.e., off-loading) is crucial to the healing process (A-I) [200, 201]. Many types of devices can off-load the infectedwound, but it is important to choose one that permits easy inspection [202].

Adjunctive treatments. Investigators and industry repre-

sentatives have advocated many types of wound-care treat-ments, including wound vacuum-drainage systems [203206],

recombinant growth factors [207212], skin substitutes [203,213216], antimicrobial dressings [217219], and maggot (ster-ile larvae) therapy [220222]. Although each treatment likely has some appropriate indications, for infected wounds, avail-able evidence is insufcient to recommend routine use of any of these modalities for treatment or prophylaxis.

Two adjunctive modalities do deserve brief comments. First,granulocyte colony-stimulating factors (G-CSFs) have now been investigated in 5 randomized trials involving diabetic footinfections [223227]. A preliminary meta-analysis of these trialssuggests that G-CSF does not accelerate resolution of infectionbut may signicantly reduce the need for operative procedures

(B-I) [228]. Second, several anecdotal and retrospective reportssuggest that hyperbaric oxygen therapy may be of value fortreatment of diabetic foot wounds, and a few recent prospectivestudies have shown promising results [229232]. A recentCochrane review concluded that hyperbaric oxygen therapy signicantly reduced the risk of major amputation related to adiabetic foot ulcer [233] (B-I). Only additional randomizedclinical trials can establish when, for whom, and with whatprotocols these expensive and limited resources might be usedin the treatment of diabetic foot infections. Neither should beused as a substitute for proper surgical debridement and con-ventional therapy.

FOLLOW-UP

Careful observation of the patients response to therapy (gure4) is essential and should be performed daily for inpatients andperhaps every 25 days initially for outpatients (B-III). Theprimary indicators of improvement are resolution of local andsystemic symptoms and clinical signs of inammation. Bloodtest ndings, including WBC counts [234, 235] and inam-


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Table 8. Suggested empirical antibiotic regimens, based on clinical severity, for diabetic foot infections.

Route and agent(s) Mild Moderate Severe

Advised route Oral for most Oral or parenteral, basedon clinical situation andagent(s) selected

Intravenous, at leastinitially

Dicloxacillin Yes Clindamycin Yes

Cephalexin Yes Trimethoprim-sulfamethoxazole Yes Yes Amoxicillin/clavulanate Yes Yes Levooxacin Yes Yes Cefoxitin Yes

Ceftriaxone Yes Ampicillin/sulbactam Yes Linezolid a (with or without aztreonam) Yes Daptomycin a (with or without aztreonam) Yes Ertapenem Yes Cefuroxime with or without metronidazole Yes Ticarcillin/clavulanate Yes Piperacillin/tazobactam Yes YesLevooxacin or ciprooxacin with clindamycin Yes YesImipenem-cilastatin Yes

Vancomycin a and ceftazidime (with or withoutmetronidazole)

Yes

NOTE. Denitive regimens should consider results of culture and susceptibility tests, as well as the clinical response to the empiricalregimen. Similar agents of thesame drug class maybe substituted.Some of these regimens maynot have US Food andDrugAdministrationapproval for complicated skin and skin-structure infections, and only linezolid is currently specically approved for diabetic foot infections.

a For patients in whom methicillin-resistant S. aureus infection is proven or likely.

matory markers, such as the erythrocyte sedimentation rate[122, 236, 237] and the C-reactive protein level [238], are of limited use for monitoring response, although is it reassuringto see elevated levels decrease and cause for concern when they do not.

When a hospitalized patient is ready for discharge or anoutpatient returns for follow-up, the clinician should accom-plish 4 tasks (gures 1, 2, and 4).

1. Select the denitive antibiotic regimen.Review the cultureand drug susceptibility results and inquire about any adverseeffects related to the current antibiotic therapy. Choose a de-nitive antibiotic regimen (including the treatment duration)on the basis of the results of cultures, imaging, or other in-vestigations, and the initial clinical response (C-III). It is not

always necessary to cover all microorganisms isolated from cul-tures. More virulent species (e.g., S. aureus and group A or Bstreptococci) should always be covered, but in a polymicrobialinfection, less-virulent bacteria (e.g., coagulase-negative staphylococci and enterococci) may be less important (B-II). If theinfection has not responded to the empirical regimen, selectagents with activity against all isolates. For a clinically stablepatient who has had 1 unsuccessful courses of therapy, con-

sider discontinuing antimicrobials for a few days and then col-lecting optimal specimens for culture (C-III).

2. Re-evaluate the wound. Inspect the site to ensure thatthe infection is responding and that the wound is healing. If neither is occurring, reassess the need for surgical intervention.No evidence supports giving antibiotics for the entire time thatthe wound remains open. Antibiotics should be used for aperiod dened by the biology of the infection and by the clinicalsyndrome, as suggested in table 9 (A-II). If clinical evidence of infection persists beyond the expected duration, check on thepatients compliance with antibiotics and re-evaluate for un-addressed adverse biological factors (gure 3). These may in-clude the development of antibiotic resistance, a superinfection,an undiagnosed deep abscess or case of osteomyelitis, or is-

chemia that is more severe than was initially suspected.3. Review the off-loading and wound care regimens.Deter-

mine the effectiveness of, and the patients compliance with,the prescribed regimens. Suggest (or seek consultation for) al-ternatives when necessary.

4. Evaluate glycemic control.Ensure that blood glucose lev-els and other aspects of the patients metabolic status are ad-equately controlled.


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Figure 3. Algorithm 1, part 3: approach to assessing a diabetic patient with a foot infection who is not responding well to treatment. TcPO2,transcutaneous partial pressure of O2.

OSTEOMYELITIS

Dealing with osteomyelitis is perhaps the most difcult andcontroversial aspect in the management of diabetic foot infec-tions [239244]. First among several problems is that the lack of a consensus denition of the disease hinders the comparisonof available studies and experiences. Next, there are many avail-able diagnostic tests, but they often yield equivocal results. Fur-thermore, the presence of osteomyelitis increases the likelihoodof surgical intervention, including amputation, and the re-quired duration of antibiotic therapy [240]. Finally, osteomy-elitis impairs healing of the overlying wound and acts as a focusfor recurrent infection.

When to consider the diagnosis. Consider osteomyelitis asa potential complication of any deep or extensive ulcer, espe-cially one that is chronic or overlies a bony prominence (gure5) [245]. Suspect underlying osteomyelitis when an ulcer does

not heal after at least 6 weeks of appropriate care and off-loading. Any ulcer in which bone is either visible or can beeasily palpated with a sterile blunt metal probe is likely to becomplicated by osteomyelitis [83]. In patients with a limb-threatening infection, positive results of a probe-to-bone testmay be taken as nearly sufcient for diagnosis, but the per-formance characteristics of this test have not yet been fully dened. A swollen foot in a patient with a history of foot


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Figure 4. Algorithm 2: approach to selecting antibiotic therapy for a diabetic patient with a foot infection. MRSA, methicillin-resistantStaphylococcus aureus .

ulceration, a sausage toe (i.e., a red, swollen digit) [246], oran unexplained high WBC count [235] or inammatory mark-ers [236] should also arouse suspicion of osteomyelitis (B-II).Finally, radiologically evident bone destruction beneath an ulcershould be considered to represent osteomyelitis unless provenotherwise [247].

Conrming the diagnosis. Because bony destruction isusually not seen on plain radiography performed during theearly stages of disease and neuro-osteoarthropathy can mimic

infection, diagnosing osteomyelitis at the time the patient rstpresents to the hospital can be difcult [248250]. Character-istic progressive changes on serial plain radiographs may helpin more-chronic cases [247, 251]. Radioisotope scans are moresensitive than radiographs for detecting osteomyelitis duringthe early stages of this diseases, but they are expensive and canbe time-consuming [252]. The reported performance charac-teristics of various types of nuclear medicine scans varies, butthe specicity of technetium bone scans is generally low [240,


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Table 9. Suggested route, setting, and durations of antibiotic therapy, by clinical syndrome.

Site, by severity orextent, of infection Route of administration Setting for therapy Duration of therapy

Soft-tissue onlyMild Topical or oral Outpatient 12 Weeks; may extend

up to 4 weeks if slowto resolve

Moderate Oral (or initial parenteral) Outpatient/inpatient 24 WeeksSevere Initial parenteral, switch to oral

when possibleInpatient, then

outpatient24 Weeks

Bone or jointNo residual infected tissue

(e.g., post-amputation)Parenteral or oral 25 Days

Residual infected soft tissue(but not bone)

Parenteral or oral 24 Weeks

Residual infected (but viable)bone

Initial parenteral, then consideroral switch

46 Weeks

No surgery, or residual deadbone postoperatively

Initial parenteral, then consideroral switch

1 3 Months

253255]. MRI is the most useful of the currently availableimaging modalities (A-I) [90, 92, 94, 256259]. MRI is themost accurate imaging study for dening bone infection, andit also provides the most reliable image of deep soft-tissueinfections. The performance characteristics of all these diag-nostic tests are highly correlated with the pretest probability of osteomyelitis, and they are most useful for intermediately prob-able cases [260]. The criterion (gold) standard for diagnosingosteomyelitis is isolation of bacteria from a reliably obtainedsample of bone (using measures to minimize contamination)concomitant with histological ndings of inammatory cells

and osteonecrosis (B-II). Unfortunately, few of the studies thathave evaluated diagnostic tests or have assessed treatment out-comes have used this standard.

MRI is usually not needed as a rst-line investigation in casesof diabetic foot infection. When osteomyelitis is a possibility,obtaining plain radiographs often sufces. If these radiographsshow no evidence of pathological ndings in bone, the patientshould be treated for 2 weeks for the soft-tissue infection. If suspicion of osteomyelitis persists, perform plain radiography again 24 weeks later. If the initial lms show classic changessuggestive of osteomyelitis (cortical erosion, periosteal reaction,and mixed lucency and sclerosis), and if there is little likelihoodof a noninfectious osteoarthropathy, treat for presumptive os-teomyelitis, preferably after obtaining appropriate specimensfor culture (B-III). If ndings of radiography are only consistentwith, but not characteristic of, osteomyelitis, one of the fol-lowing choices should be considered.

1. Additional imaging studies.MRI is the preferred imagingstudy, with nuclear medicine scans (that preferably use newergeneration leukocyte [239, 261, 262] or immunoglobulin [263,264] techniques) being a second choice. If results of the imaging

tests are negative, osteomyelitis is unlikely; if results suggestosteomyelitis, consider whether bone biopsy is needed (videinfra).

2. Empirical treatment. Provide antibiotic therapy for an-other 24 weeks and then perform radiograph again to deter-mine whether bony changes have progressed (which wouldsuggest infection).

3. Bone biopsy. Use an appropriate procedure, as denedbelow. Collection of a sample of a bony lesion (either opera-tively or percutaneously) is recommended if the diagnosis re-mains in doubt after imaging or if osteomyelitis is likely but

the etiologic agent or antibiotic susceptibilities are not pre-dictable (B-II) [251, 265268]. Some physicians would alsoobtain biopsy specimens of most mid- or hind-foot lesions,because these are more difcult to treat and more often leadto a high-level (i.e., above the ankle) amputation. Any properly trained physician (e.g., an orthopedic surgeon, podiatrist, in-terventional radiologist) can perform the biopsy. Percutaneousbiopsy should preferably be done under uoroscopic or CTguidance, traversing uninvolved skin if possible. For patientswith sensory neuropathy, anesthesia may be unnecessary. Var-ious types of bone-cutting needles, such as Jamshidi (PerfectumCorporation; distributed by Propper and Sons) and Ostycut(Bard Products; distributed by Angiomed) have been used. Ob-tain 23 specimens if possible, sending at least 1 for cultureand another for histological analysis [269]. With small toebones, it may only be possible to aspirate a few bony spicules.We found no published reports of complications of foot bonebiopsy and consider it to be a safe procedure (B-II). Culturesof bone specimens provide more accurate microbiologic datathan do those of soft-tissue specimens for patients with oste-omyelitis [93, 268, 270].


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Figure 5. Algorithm 3: evaluating a diabetic patient who has suspected osteomyelitis of the foot.1Cortical erosion, periosteal reaction, lucencyand sclerosis, sequestrum, or involcrum.2May be done percutaneously or operatively, preferably after antibiotic therapy has been stopped for 12weeks (if safe to do so).

Choosing between medical and surgical therapy. Trad-itionally, authorities have believed that resecting a bone withchronic osteomyelitis was essential for cure [240, 265]. Recently,some have disputed the routine need for surgical resection[239]. Denitive surgical solutions to osteomyelitis, such as ray and transmetatarsal amputations, may risk architectural reor-ganization of the foot, resulting in altered biomechanics andadditional cycles of ulceration. Neuropathy and reduced sys-temic manifestations of infection may make osteomyelitis tol-erable for the patient, who may thus opt for attempts at medicalmanagement. By contrast, these diabetic complications may

also mask progressive bone destruction, with delayed or in-adequate surgery resulting in poorly controlled infection, ad-ditional bone or soft-tissue necrosis, and a nonhealing wound.

These arguments have led some health care professionals totreat diabetic foot osteomyelitis with little or no surgical in-tervention [239]. Published reports on nonsurgical treatmentwith a prolonged (36 months) course of antibiotics have re-ported clinical success in 65%80% of cases [155, 173, 237,243, 271276]. Unfortunately, these nonrandomized case seriesoften fail to specify a denition of osteomyelitis, how patientswere selected, whether patients were enrolled prospectively or


19/26


20/26


for the diagnosis and treatment of infections, especially osteomyelitis.

6. Compare the outcomes of surgical and nonsurgicalman-agement of osteomyelitis.

Acknowledgments

Conict of interest. B.A.L.: Advisory board membership, research sup-port from, or speakers bureau for Pzer, Merck, Wyeth-Ayerst, Cubist,Vicuron, and Ortho-McNeil. A.R.B.: Speakers bureau for Pzer. H.G.D.:Speakers bureau for GlaxoSmithKline and Pzer, and research supportfrom Theravance. J.M.E.: Advisory board membership, research supportfrom, or speakers bureau for AstraZeneca, Bayer, Bristol-Myers Squibb,Eli Lilly, Fujisawa, Janssen Ortho, and Pzer. W.S.J.: Consultant andspeakers bureau for Pzer and Merck. A.W.K.: Research support fromBayer, Pzer, Merck, Ortho-McNeil, Cubist, Pharmacia, Vicuron, and Fu- jisawa and advisory board forAventis,Pzer,King Pharmaceuticals,Chiron,Vicuron, Cubist, and Bayer. C.N.: Former employee of Pzer. J.S.T.: Re-search support from and speakers bureau for Wyeth, Merck, Pzer, Ortho-McNeil, Bayer, and Glaxo-SmithKline. J.L.L. and D.P.L.: No conict.

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