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Diagnosis and Treatment of Diabetic Foot Infections
Benjamin 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. Tan11
Medical 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, Nuffield Orthopaedic Centre, Oxford, United Kingdom; 3 Northern 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; 6Division of Infectious Diseases, Department of Medicine, Harvard Medical School, and Beth Israel Deaconess Medical Center, Boston, Massachusetts; 7 Dimensional 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; 10Department of Medicine, New Jersey School of Medicine and Dentistry, and Cooper Hospital, Camden, New Jersey; and 11Department of Internal Medicine, Summa Health System, and Northeastern Ohio Universities College of Medicine, Akron, Ohio

EXECUTIVE SUMMARY 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary footcare team (A-II) (table 1). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic

Received 2 July 2004; accepted 2 July 2004; electronically published 10 September 2004. These guidelines were developed and issued on behalf of the Infectious Diseases Society of America. a B.A.L. served as the chairman and A.R.B. served as the vice chairman of the Infectious Diseases Society of America Guidelines Committee on Diabetic Foot Infections. b Deceased. Reprints or correspondence: Dr. Benjamin A. Lipsky, Veterans Affairs Puget Sound Health Care System, S-111-GIMC, 1660 S. Columbian Way, Seattle, WA 981089804 ( Clinical Infectious Diseases 2004; 39:885–910 This article is in the public domain, and no copyright is claimed. 1058-4838/2004/3907-0001

wounds or who have recently received antibiotic therapy may also be infected with gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture prior to starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (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 the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treatGuidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 885

Table 1. Infectious Diseases Society of America–United States Public Health Service Grading System for ranking recommendations in clinical guidelines.
Category, grade Strength of recommendation A B C D E Quality of evidence I II Definition Good evidence to support a recommendation for use; should always be offered Moderate evidence to support a recommendation for use; should generally be offered Poor evidence to support a recommendation; optional Moderate evidence to support a recommendation against use; should generally not be offered Good evidence to support a recommendation against use; should never be offered Evidence from у1 properly randomized, controlled trial Evidence from у1 well-designed clinical trial, without randomization; from cohort or casecontrolled analytic studies (preferably from 11 center); from multiple time-series; or from dramatic results from uncontrolled experiments Evidence from opinions of respected authorities, based on clinical experience, descriptive studies, 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 insufficient 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 sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broadspectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic 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. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 1–2 weeks usually suffices, but some require an additional 1–2 weeks; for moderate and severe infections, usually 2–4 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 4–6 weeks is required, but a shorter duration is sufficient if the entire infected bone is

removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to у1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb’s arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate 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 insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoar-

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

high-quality care is usually no more difficult to achieve or expensive than poor care and its consequences [20. leading to unattended minor injuries caused by excess pressure or mechanical or thermal injury Deficient sweating leading to dry. Charcot disease) or limited joint mobility Vascular (arterial) insufficiency Hyperglycemia and other metabolic derangements Patient disabilities Maladaptive patient behaviors Health care system failures Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 887 . Although this field has matured. diagnosing osteomyelitis. and adjunctive treatments. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection. In addition to causing severe morbidities. Mechanism of injury or impairment Abnormal foot anatomy and biomechanics. high arch. financial. INTRODUCTION Purpose of the guideline. or have ready access to. 15]. and previous amputation(s) Inadequate adherence to precautionary measures and foot inspection and hygiene procedures. psychological distress. and ulcers Lack of protective sensation. excessive weightbearing. Risk factor Peripheral motor neuropathy may result from a lack of understanding of current diagnostic and therapeutic approaches. 19. and costly problem [1–4]. wound care. Use of this guideline may reduce the burdens (medical. Vincent declaration [22]. including those related to antibiotic prescribing. however. 7]. wound healing. for defining the pathogenic organism(s). further research is much needed. these infections are frequently inadequately managed [16]. but bone biopsy is valuable for establishing the diagnosis of osteomyelitis. The committee members realize that the realities of primary care practice and the scarcity of resources in some clinical situations will restrict the implementation of some of the recommended procedures and treatments. leading to excess pressure. limited mobility. Clinical examination and imaging tests may suffice. Diabetic foot infections require careful attention and coordinated management. We hope it will contribute to reducing the rates of lower extremity amputation. leading to excess pressure. and delivery of neutrophils Impaired immunological (especially neutrophil) function and wound healing and excess collagen cross-linking Reduced vision. and clarifying the role of surgery in treating osteomyelitis (A-III). they now account for the largest number of diabetes-related hospital bed–days [5] and are the most common proximate. Foot infections in persons with diabetes are a common. the need for and duration of hospitalization. The team managing these infections should preferably include. This Table 2. preferably by a multidisciplinary foot-care team (A-II) [8–13]. whereas others will need increased resources. and the incidence of major limb amputation [14. with clawing of toes. 21]. poor compliance with medical care. and poor footwear Inadequate patient education and monitoring of glycemic control and foot care Peripheral sensory neuropathy Peripheral autonomic neuropathy Neuro-osteoarthropathic deformities (i. and subluxed metatarsophalangeal joints. surgical procedures. nontraumatic cause of amputations [6.e. and intensified coordination of available expertise. Optimal management of diabetic foot infections can potentially reduce the incidence of infection-related morbidities. or a lack of effective multidisciplinary collaboration. and for determining the antibiotic susceptibilities of such organisms (B-II). that in almost all settings. Unfortunately. We believe. insufficient resources devoted to the problem. cracking skin Abnormal anatomy and biomechanics. better staff training.thropathy. in line with the international St. especially in the midplantar area Impaired tissue viability.. diagnostic testing. inappropriate activities. because other published guidelines cover the general management of the diabetic foot and diabetic foot ulceration [17–19]. complex. This guideline should provide a framework for treating all diabetic patients who have a suspected foot infection. The primary purpose of this guideline is to help reduce the medical morbidity. The focus of this guideline is primarily on managing the diabetic patient with suspected or evident foot infection. and financial costs associated with diabetic foot infections. Some health care centers will be able to implement it immediately. callus formation. defining optimal antibiotic regimens in various situations. and ecological) associated with inappropriate practices. hospitalization decisions. Cost savings may en- Risk factors for foot ulceration and infection. an infectious diseases specialist or a medical microbiologist (B-III) [1].

Methodology. the Cochrane Library. methicillin-resistant S. diagnostic testing (especially MRI). including enterococci. c Usually polymicrobial. These 888 • CID 2004:39 (1 October) • Lipsky et al. C. may affect some diabetic patients. Various poorly characterized immunologic disturbances. include paronychia. This sequence of events can be rapid (occurring over days or even hours). Pseudomonas aeruginosa. these served as a basis for the final document. B. the infection can involve deeper tissues. Because of the relative paucity of randomized controlled trials or other high-quality evidence in this field. coagulase-negative staphylococci. This wound may progress to become actively infected. myositis. especially. aureus. and G. especially in an ischemic limb. other nonfermentative gram-negative rods [39–43]. b a sue. tendonitis. with disturbances of sensory. their backgrounds represent academia. aureus and b-hemolytic streptococcusa Foot-infection syndrome Cellulitis without an open skin wound Infected ulcer and antibiotic naiveb Infected ulcer that is chronic or was previously treated with S. Chronic wounds develop a more complex colonizing flora.d Pseudomonas aeruginosa (often in combination with other organisms) Aerobic gram-positive cocci (S. and. Thus. Neuropathy plays the central role. sometimes. especially those that involve polymorphonuclear leukocytes. the EBSCO database. and hand-searching of bibliographies of published articles). which published its International Consensus Guidelines on Diagnosing and Treating Diabetic Foot Infections in 2003 [23]. and autonomic functions leading to ulceration due to trauma or excessive pressure on a deformed foot that lacks protective sensation. Enterobacteriaceae. motor. infectious diseases clinical practice. and. The most common and classical lesion. aureus . by contiguous extension. possibly. many of whom also have experience in writing guidelines. and c antibiotic therapy Enterobacteriaceae Ulcer that is macerated because of soakingc Long duration nonhealing wounds with prolonged. and vascular interventions [12]. Once the protective layer of skin is breached. nonfermentative gram-negative rods. Pseudomonas species. Committee members are from several US states and other countries. broadspectrum antibiotic therapyc. After an extensive literature search (which included the MEDLINE database. and obligate anaerobes “Fetid foot”: extensive necrosis or gangrene. vancomycin-resistant enterococci. C. underlying tissues are exposed to bacterial colonization. committee members reviewed and discussed all available evidence in a series of meetings and established consensus through discussion and debate over a period of 3 years. and G. Pathogens b-Hemolytic streptococcusa and Staphylococcus aureus S. although this may be offset by an increased demand for preventive foot care.Table 3. but especially group B) are the most commonly isolated pathogens [31–38]. Pathogens associated with various clinical foot-infection syndromes. nonfermentative gramnegative rods. obligate anaerobes. This wound results from a complex amalgam of risk factors [25. surgical procedures. abscesses. is the infected diabetic “mal perforans” foot ulcer. various Enterobacteriaceae. Often monomicrobial. which underwent numerous revisions that were based on both internal and external reviews. b-hemolytic streptococcus. and these likely increase the risk and severity of foot infections [27–30]. and osteomyelitis. MRSA or vancomycin-resistant enterococci [VRE]) [44]. d Antibiotic-resistant species (e. or extended-spectrum b-lactamase producing gram-negative rods) are common. and industry. and enterococci). S.. Al- . and. cellulitis. septic arthritis. and. Enterobacteriaceae. 26]. including enterococci.g. Three of the members are also members of the International Working Group on the Diabetic Foot. diabetic foot Web sites and bibliographies. we elected to offer a relatively brief summary and to provide an extensive bibliography for those who would like to review the data themselves.. most of our recommendations are based on discussion and consensus (B-II) (table 1) [24]. Hospitalization. aureus and the b-hemolytic streptococci (groups A. diphtheroids. MICROBIOLOGY Aerobic gram-positive cocci are the predominant microorganisms that colonize and acutely infect breaks in the skin. PATHOPHYSIOLOGY OF INFECTION A diabetic foot infection is most simply defined as any inframalleolar infection in a person with diabetes mellitus. bench and clinical research. prolonged or broad-spectrum antibiotic therapy may predispose patients to colonization and/or infection with antibiotic-resistant organisms (e. fungi Mixed aerobic gram-positive cocci. podiatry. however. which are summarized in table 2. Three subcommittees drafted subsections that were modified and exchanged. This guideline committee is comprised of Infectious Diseases Society of America members with experience and interest in diabetic foot infections. malodorousc Groups A. aureus.g. necrotizing fasciitis.

50]. 43. 36. to assume a pathogenic role [43. including gram-positive and gram-negative aerobes and anaerobes [14. aureus has been isolated in several countries. 34. 51]. The pathogenic role of each isolate in a polymicrobial infection is often unclear. part 1: approach to treating a diabetic patient with a foot wound though MRSA strains have previously been isolated mainly from hospitalized patients. aureus each involved a diabetic patient with a foot infection [49]. Table Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 889 . Of note. 41. The impaired host defenses around necrotic soft tissue or bone may allow low-virulence colonizers. Algorithm 1. Cultures of specimens obtained from patients with such mixed infections generally yield 3–5 isolates. 40. community-associated cases are now becoming common [45] and are associated with worse outcomes in patients with diabetic foot infections [46–48]. Vancomycin (or glycopeptide)–intermediate S. such as coagulase- negative staphylococci and Corynebacterium species (“diphtheroids”).Figure 1. 37. Acute infections in patients who have not recently received antimicrobials are often monomicrobial (almost always with an aerobic grampositive coccus). 38. 52–58]. the first 2 reported cases of vancomycin-resistant S. whereas chronic infections are often polymicrobial [31.

impaired cognition. stasis. monofilament pressure. and involvement of muscle. and radiography (у2 images) Gram staining and culture. extent. claw/hammer toes. chills. including Charcot arthropathy. or gangrene Edema. tachypnea hyperosmolality. pain. Level of evaluation. blood pressures (ABI). azotemia. fasciitis. or joint Purulence. friends. acidosis Delirium. and osteomyelitis . and health care professionals Clinical foot examination and radiography (у2 images) Psychological/cognitive state Social situation Limb or foot Biomechanics Vascular status Arteriala Venous Neuropathy Wound Size and depth (tissues involved) Presence. or vibration perception Inspect. sweats. and angiograms Skin and soft-tissue examination and duplex ultrasonography Light touch. debride. bone. induration. and stupor Self neglect. necrosis. crepitus. abscess. or thrombosis Loss of protective sensationb Investigations History and physical examination Serum chemistry analyses and hematological testing Assessment of mental and psychological status Interviews with family. gangrene.c and probed the wound. hypotension. tenderness. cellulitis.e ultrasonography or CT for detection of deep abscesses. duplex ultrasonography.Table 4. and lack of home support Deformities. and cause of infection Foot pulses. TcpO2. vomiting. tendon. foreign body. and callosities Ischemia. warmth. by area(s) to be assessed Patient Systemic response to infection Metabolic state 890 Relevant problems and observations Fever. and radiography (у2 images) and/or MRI for detection of osteomyelitisf Necrosis. hyperglycemia. potential noncompliance. and tachycardia Volume depletion. depression. bullae. dementia. Evaluating the diabetic patient who has an infected foot.

(4) TcpO2 [70]. and permits examination for the presence of deep-tissue involvement [17. which may provide the best guidance to determine the anatomic level at which the limb is adequately perfused (TcpO2. Following debridement. 76]. other diagnostic tests are indicated [63]. Tests are available to measure the following: (1) Doppler arterial pressure. and the pathogens obtained from cases of cellulitis are predictably aerobic gram-positive cocci. f Ultrasonography (especially high resolution) [88] and CT scanning [89] may be helpful for detecting deep soft-tissue abscesses or sinus tracts. but this method is insensitive. c Most wounds need debridement. 79–82]. (2) ABI.50 suggests ischemia that will likely impair wound healing [66]. because these generally provide more accurate culture results than do superficial swab specimens (A-I). 77. ankle-brachial index (ratio of systolic blood pressures from arm and foot). metal probe to measure the depth and extent of the wound. If in doubt. See table 5 for details of sampling methods. Debridement reduces pressure at callused sites. the extent of surrounding cellulitis.50–0. metatarsal heads and arch. a 891 . which involves removing both the hyperkeratosis (callus) surrounding a wound and the necrotic tissue and slough from its base. removes colonizing bacteria. Values must be interpreted cautiously when there is arterial calcification [59. but a vascular specialist (medical or surgical) may need to interpret the results. communications with joint cavities or tendon sheaths. which is suggested by ABIs of 11 [68]. 130 mm Hg) tissue [71–74] but can lack reproducibility. arterial supply is generally adequate [60–62]. Obtain specimens for culture before initiating antibiotic therapy (if possible) or after discontinuing therapy (in a stable patient who has not responded to therapy) for a few days (B-III). 85] indicate that the latter yield a greater range of organisms than do deeper-tissue material and yet may still fail to identify some of the deep flora. and an ABI of ! 0. blunt. defined by the inability to detect a 10-g nylon monofilament (SemmesWeinstein) when pressed against any 2 of 3 sites (chosen from among 5) on the foot (plantar surface of heel. with specially designed cuffs. but properly collected and transported anaerobic swab specimens may be adequate [86]. Standard swab specimens yield fewer anaerobes and are often minimally processed by the microbiology laboratory. MRI may also provide anatomic information about the presence of a sinus tract. ABI. abscess. An ABI of 0. 42. facilitates the collection of appropriate specimens for culture. e Knowledge of the etiologic agent(s) that caused the wound infection is generally helpful in selecting definitive antibiotic therapy. 64–69]. 84. Any trained individual can perform these tests. Nuclear medicine scans (especially those with labeled leukocytes and. or muscle involvement [90–93].90 identifies mild-to-moderate peripheral vascular disease. soft-tissue abscesses. Skin aspiration may yield a pathogen in cases of cellulitis [87]. sometimes. obtain and process specimens by means of appropriate methods.NOTE. Bone touched with a probe has a characteristic stony feel [83]. including noting any foreign bodies. b Peripheral neuropathy is most easily detected by loss of protective sensation. and tips of toes) [25. To avoid contaminants. with waveform analysis. Most studies [41. 78]. and the quality and quantity of any drainage (including color and odor)—this aids any other clinicians who are treating the patient in their assessment of the healing progress (B-III). or palpable bone (A-II). transcutaneous partial pressure of oxygen. (3) Ankle blood pressure (should be 150 mm Hg) and toe pressure (should be 130 mm Hg). Attempt to obtain tissue samples. measure and record the wound size. and they require a skilled technician and relatively expensive equipment [75. Assess the foot’s arterial supply in every patient with a diabetic foot infection (A-II) [59]. of bone) are highly sensitive and may be useful in some cases [94–97] but are generally less specific than MRI. d Use a sterile. The patient should be forewarned that bleeding is likely and that the wound will be larger after the procedure. TcpO2. If dorsalis pedis and posterior tibial pulses are palpable. Plain radiographs and MRIs are best for detecting bone involvement (A-I).

and the presence of any systemic consequences of infection. 7 Blood cultures should be performed for a patient with a severe infection. Other classification schemes have used the terms “uncomplicated” and “complicated” synonymously with mild and moderate. some of which can be quite complicated and even limb threatening. Clinicians lacking the skills or experience to conduct any of these assessments should seek appropriate consultation. which tissues are involved) and whether the wound is complicated by either ischemia or infection [23. 7 Needle aspiration may be useful for obtaining purulent collections or. unless done as part of an infection-control surveillance protocol (C-III). because this term covers a broad spectrum of wounds. warmth. Management of diabetic foot infections involves evaluating and determining the severity of infection as the basis for selecting the appropriate approach to treatment [15. AND THE INFECTION Diabetic patients may develop many types of foot wounds. the lack of consensus on wound definitions and infection classification systems hampers comparison of published studies.” Infections defined as “mild” must be distinguished from clinically uninfected lesions but are otherwise relatively easy to recognize. grades 2–4 are similar to those we describe in table 6. perhaps. and pain or tenderness). it includes a category of grade 1 for uninfected lesions. and 4 (presence of a systemic inflammatory response syndrome). 40] (B-II). the most important initial task is to recognize patients who require immediate hospitalization. 101. 7 Clearly identify samples (specimen type and anatomic location). any contribution of altered foot biomechanics to the cause of the wound (and. and sensation). 106–108] (BII). as outlined in tables 4 and 5 (B-III): the patient as a whole. and the infected wound. is skewed toward severe disease. any contribution of vascular (especially arterial) disease. 99] has been widely used for 25 years but was developed for the “dysvascular” foot. depth/tissue loss. For infected wounds (figure 2). Defining infections as “moderate” poses the greatest difficulty. DETERMINING THE SEVERITY OF INFECTION The results of the evaluations described in table 4 can be used to determine the overall severity of the infection and to formulate a management plan (figure 2) (B-II). a specimen from an area of cellulitis. healing of an ulcer. The distinction between moderate and severe infections has less to do with the status of the foot than Collection of soft-tissue specimens from an infected diabetic foot for culture. extent/size. swelling or induration. the affected limb or foot. Unfortunately. especially if the patient is systemically ill (C-III). How 7 Cleanse and debride the lesion before obtaining specimens for culture. 98. We have defined these potentially lifethreatening infections as “severe. not all ulcers are infected (figure 1) (B-II) [23]. obtain tissue specimens from the debrided base (whenever possible) by means of curettage (scraping with a sterile dermal curette or scalpel blade) or biopsy (bedside or operative) (A-I). use a swab designed for culturing aerobic and anaerobic organisms and rapidly transport it to the laboratory (B-I). and promptly send them to the laboratory in an appropriate sterile container or transport media for aerobic and anaerobic culture. but may be unnecessary in cases of acute mild infection in an antibiotic-naive patient (B-III). The Table 5. Consensus is developing that the key issues in classifying a diabetic foot wound are its depth (in particular. parenteral and broad-spectrum empirical antibiotic therapy. Because this research-based system is designed to be applicable to all ulcers. 892 • CID 2004:39 (1 October) • Lipsky et al. 7 In cases involving an open wound. 3 (extensive cellulitis or deeper infection). 2 (involvement of skin and subcutaneous tissue only). The goal is to determine the clinical extent (table 4) and the microbial etiology (table 5) of the infection. Evaluation of the infection should occur at 3 levels. The infection category includes grades 1 (no infection). 7 Avoid swabbing undebrided ulcers or wound drainage. 40. and urgent consideration of diagnostic testing and surgical consultation. When 7 Culturing clinically uninfected lesions is unnecessary. The key elements are summarized by the acronym PEDIS (perfusion. but is not defined by. EVALUATING THE PATIENT. The International Consensus on the Diabetic Foot recently published a preliminary progress report on a diabetic foot ulcer classification system for research purposes [23]. its ability to heal). 23. The issue of osteomyelitis is particularly complex and problematic and is thus dealt with separately.3 lists common clinical infection syndromes and the pathogens most likely isolated in conjunction with them. Wagner system [15. thus. the biology or pathogenesis of the wound. If swabbing the debrided wound base is the only available culture option. Curing an infection often contributes to. THE WOUND. 7 Cultures of infected wounds are valuable for directing antibiotic choices. but we wish to avoid confusion with the various complications that can beset a wound. Infection should be diagnosed clinically on the basis of the presence of purulent secretions (pus) or at least 2 of the cardinal manifestations of inflammation (redness. and contains all infections within a single grade [100–105]. infection. any of which can become infected. .

1Consider hospitalization if any of the following criteria are present: systemic toxicity (e. we discourage therapy of uninfected ulcers. severe hypoglycemia or acidosis). requirement of urgent diagnostic or therapeutic interventions. we propose the one presented in table 6 as a basis for subsequent discussions in and beyond this guideline (B-II). Because antibiotic use encourages antimicrobial resistance.g. and inability to care for self or inadequate home support. fever and leukocytosis). it is difficult to decide whether a chronic wound is infected. they contain a high “bioburden” of bacteria (usually defined as 1105 organisms per gram of tissue) that results in “critical colonization” levels and impairs wound healing [54. Available published evidence does not support the use of antibiotics for the management of clinically uninfected ulcerations. Some argue that many apparently uninfected diabetic foot ulcers are actually subclinically infected—that is. part 2: approach to treating a diabetic patient with a foot infection. such as when the foot is ischemic. with the patient to whom it is attached. Algorithm 1. rapidly progressive or deeptissue infection.Figure 2. After debating several classification schemes. either to enhance wound healing or as prophylaxis against infection [115. substantial necrosis or gangrene.. incurs financial cost. has abnormal colGuidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 893 . 116]. metabolic instability (e. TREATMENT OF INFECTION Avoid prescribing antibiotics for uninfected ulcerations. In some circumstances. and may cause drug-related adverse effects. This distinction is complicated by the fact that у50% of patients with a limbthreatening infection do not manifest systemic signs or symptoms.g. 109–114].. or presence of critical ischemia.

and azotemia. leukocytosis. Although anaerobic organisms are isolated from many severe infections [42. infection. In the absence of these complicating features. tachycardia. fever. There are surprisingly few published clinical trials of antibiotic therapy for diabetic foot infection. or when an otherwise properly treated ulcer fails to show healing progress [117. To ensure adequate and prompt tissue concentrations. no other local complications or systemic illness. such as those covering only aerobic grampositive cocci (A-II) [84]. they are infrequent in mild-to-moderate infections [14. therapy should be given parenterally. and deciding on its necessity requires consideration of both medical and social issues. deep-tissue abscess. For mildly infected open wounds with minimal cellulitis. Critically ill patients who require surgery should usually be stabilized before transfer to the operating room. urgent diagnostic testing. 120]. 122]. tenderness. most patients with mild or moderate infections can be treated as outpatients (A-II) [84. but any cellulitis/erythema extends р2 cm around the ulcer. In these unusual cases. For severe infections and for more-extensive. These should have activity against gram-positive cocci (including MRSA in locations where this pathogen is common). although surgery should usually not be delayed for 148 h after presentation to the hospital (B-III) [123]. Foot ischemia may increase the severity of any infection. Stabilize the patient. and treatment of other exacerbating disorders. and sensation. Infection (as above) in a patient who is systemically well and metabolically stable but which has у1 of the following characteristics: cellulitis extending 12 cm. and the specific drugs to administer and later involves choosing the definitive 894 • CID 2004:39 (1 October) • Lipsky et al. severe hyperglycemia. Attending to the general metabolic state of the patient is essential [25. Initial therapy is usually empirical and should be based on the severity of the infection and on any available microbiological data. acidosis. especially with highly bioavailable agents (A-II). chills. regimen and the duration of treatment. Determine the need for hospitalization. As the infection improves. acidosis. or azotemia) Moderate 3 Severe 4 NOTE. 129]. rather than with diabetes [138]. or erythema. confusion. Selection of the antibiotic regimen initially involves decisions about the route of therapy. 84. warmth. has friable granulation tissue. this is associated with the pharmacodynamic properties of the specific agent and. hyperglycemia may be easier to control. extent/size. and involvement of muscle. depth/ tissue loss. lymphangitic streaking. Choose an antibiotic regimen. limited data support the use of topical antimicrobial therapy (B-I) [130]. culture-directed course of antibiotic therapy may be appropriate (C-III). spread beneath the superficial fascia. Definitions of terms can be found in footnotes to table 4. is associated with unexpected pain or tenderness. This may involve restoration of the fluid and electrolyte balances. Infection severity Uninfected Mild PEDIS a grade 1 2 Clinical manifestations of infection Wound lacking purulence or any manifestations of inflammation Presence of у2 manifestations of inflammation (purulence. the spectrum of microorganisms to be covered. a brief.Table 6. 128]. chronic moderate infections. correction of hyperglycemia. perfusion. Several antibiotic trials involving patients with various complicated .g. gangrene. hyperosmolality. a International Consensus on the Diabetic Foot [23]. For mild-to-moderate infections in patients without gastrointestinal absorption problems and for whom an oral agent with the appropriate spectrum is available. Patients with infections that are either severe or complicated by critical limb ischemia should generally be hospitalized (C-III) [119. 121]. Some patients with apparently mild infections and more patients with moderate infections may also need hospitalization. at least initially (C-III). tendon. or because complicating factors are likely to affect their wound care or adherence to antibiotic treatment. as well as gram-negative and obligate anaerobic organisms (B-III). it is safest to commence therapy with broad-spectrum agents. the arterial supply to the foot. The improvement of glycemic control may aid in both eradicating the infection and healing the wound [124]. Clinical classification of a diabetic foot infection. vomiting. and infection is limited to the skin or superficial subcutaneous tissues. joint or bone Infection in a patient with systemic toxicity or metabolic instability (e. this may be for observation. and there is little evidence to support the need for antianaerobic therapy in most infections (B-III). especially. Although some suggest broad-spectrum empirical therapy for most infections [125–127]. pain. or induration). the majority of mild—and many moderate—infections can be treated with agents with a relatively narrow spectrum. and the presence of critical ischemia often makes the infection severe. PEDIS. oral therapy is often appropriate. oration or a fetid odor.. 118]. Antibiotics vary in how well they achieve effective concentrations in infected diabetic foot lesions [131–137]. Hospitalization is the most expensive part of treating a diabetic foot infection. hypotension. such as recent culture results or current Gram-stained smear findings.

and formulate a strategy for eventual soft-tissue cover (e. 179]. lowerextremity atherosclerosis may be amenable to angioplasty or vascular bypass [186]. Elective amputation may be considered for the patient who has recurrent ulceration (despite maximal preventive measures). secondary intention. In most cases. and the experience of the prescriber and should be modified on the basis of any relevant organ (especially renal) dysfunction and other clinical factors. the surgeon should attempt to save as much of the limb as possible. depending on various clinical.9) can usually be successfully treated without a vascular Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 895 . the pathophysiology of ulceration and infection. Table 8 summarizes some potential empirical antibiotic regimens according to the clinical severity of the infection. including limited resections or amputations. provided there does not appear to be an underlying focus of infection [80. especially on the heel. amputation is the best or only option [170. deep abscesses. or tissue transfer) [175–177]. The lack of standardization among these trials makes the comparison of outcomes of different regimens inappropriate. it may be preferable (especially for a patient for whom surgery is a poor option) to let the necrotic portions autoamputate. consider common operative pitfalls (e. Seek urgent surgical consultation for life. Selection of the level of amputation must take into consideration vascular. it may be appropriate to delay surgery to carefully observe the effectiveness of medical therapy or to determine the demarcation line between necrotic and viable tissue [174]. either exclusively or as an identified subset of a larger study. Table 7 provides a list of published clinical trials that focused on therapy of diabetic foot infections. or progressive infection in the face of apparently appropriate medical care (figure 3). reconstructive.or limb-threatening infections. gas gangrene. Pus under pressure. 171]. those with an ankle to brachial artery blood pressure index of 0.5–0. The surgeon’s training specialty is less important than his or her knowledge of the anatomy of the foot. or prone to future ulceration. unlikely to heal. delayed primary closure. extensive soft-tissue loss. until they soften enough to be more easily removed. surgical treatment of diabetic foot infections is based on even less-structured evidence than that for antibiotic therapy [169]. On the basis of the available studies.g. Empirical choices for patients who are not responding to antibiotic therapy should include agents that cover a different or more-extended spectrum of organisms (B-III) (figure 3). primary closure. Determine the need for surgery. epidemiological. In most instances. the drug’s manufacturers. and rehabilitation issues [183. The regimens in table 8 are listed in approximate order of increasing broad-spectrum coverage. Similar agents could be used. However. although the available data do not allow us to recommend any specific antibiotic regimen for diabetic foot infections (B-II). or along the tendon sheaths).. The surgical approach should optimize the likelihood for healing and should attempt to preserve the integrity of the walking surface of the foot (B-II) [178]. the surgeon must have sufficient knowledge and experience to judge when and how to intervene. It may also be best to leave adherent eschars in place. Generally. 81]. 184]. ischemia is due to larger-vessel atherosclerosis.g. especially in an ischemic foot. Urgent amputation is usually required only when there is extensive necrosis or life-threatening infection [180]. no single drug or combination of agents appears to be superior to others [129]. Timely and aggressive surgical debridement. the surgeon should continue to observe the patient until the infection is under control and the wound is healing (B-III). can cause rapid and irrep- arable damage.. Many infections require surgical procedures that range from drainage and excision of infected and necrotic tissues to revascularization of the lower extremity and reconstruction of soft-tissue defects or mechanical misalignments [164–168]. In addition to manual dexterity. or evidence of compartment syndrome. 182].skin and soft-tissue infections have included some patients with diabetic foot infections. has irreversible loss of foot function. and experience with and enthusiasm for the field [8]. the patient should be referred to a surgeon with vascular expertise [185]. These suggested agents are derived from available published clinical trials and our collective experience and are not meant to be inclusive of all potentially reasonable regimens. rather than to “small-vessel disease” [68]. Dosages of antibiotic agents should be selected according to suggestions of the US Food and Drug Administration.g. For patients with less-serious infections. to the deep plantar space. Unfortunately. If the infected limb appears to be ischemic. or would require unacceptably prolonged or intensive hospital care [181. 173]. Consider modifying antibiotic therapy when culture and susceptibility results are available (C-III). a higher-level amputation that results in a more functional residual stump (even if a prosthesis is required) may be a better choice than preserving a foot that is mechanically unsound. microbiological. may reduce the need for more-extensive amputation (B-II) [172. Because vessels above the knee and below the ankle tend to be relatively spared. or those in limbs with critical ischemia (A-II) [170. and financial considerations. infection spreading among foot compartments. A surgical specialist should also evaluate patients who have unexplained persistent foot pain or tenderness and/or evidence of a deep-space infection. When all or part of a foot has dry gangrene. In some cases. The differing definitions of infection severity and clinical end points that were used in these publications highlight the need to develop a consensus classification system for future studies. Patients with noncritical ischemia (e.. the order does not indicate preferences by the committee. such as those presenting with necrotizing fasciitis. The surgeon must determine the adequacy of the blood supply to the remaining viable tissues.

mostly moderate Severe PVD Soft-tissue or bone Moderate-to-severe [149] [150] [151] [152] [153] [154] [155] [156] [157] Prospective. moderate-to-severe Moderate-to-severe Mild-to-moderate Severe limb-threatening Moderate [139] [140] [141] [142] [143] [143] [144] [140] [84] [145] [146] 48 74 18 120 RDBCT Prospective. open. noncomparative Uncontrolled. comparative RDBCT Hospitalized Hospitalized Hospitalized Hospitalized Limb-threatening Moderate-to-severe Wagner grade 2–4 wounds Complicated soft-tissue [147] [159] [160] [161] (continued) . noncomparative RDBCT Prospective. quasiprospective Ofloxacin (iv. noncomparative RDBCT RCT RCT Prospective. or ciprofloxacin (iv and/or po) Carbapenems Imipenem/cilastatin (iv) Imipenem/cilastatin (iv) Imipenem/cilastatin (iv) Ertapenem (iv) 55 420 26 214 42 90 RCT RDBCT RCT subgroup a Moderate Mild-to-moderately infected ulcers Complicated soft-tissue Soft-tissue Severe Severe limb-threatening [146] [130] [150] [158] [154] [145] Outpatients or inpatients … Hospitalized Hospitalized Prospective. uncontrolled RDBCT RDBCT Prospective. then po) Ofloxacin (po) Levofloxacin (iv or po) Trovafloxacin (po) Clinafloxacin (iv. Antibiotic agents used in published clinical studies of diabetic foot infections. levofloxacin. received other iv agents. of treated patients Antibiotic (route) Cephalosporins Cefoxitin (iv) Cefoxitin (iv) Cefoxitin (iv) Cefoxitin (iv) Cefoxitin (iv) alone Cefoxitin (iv) and amdinocillin (iv) Ceftizoxime (iv) Ceftizoxime (iv) Cephalexin (po) Ceftriaxone (iv) Penicillins Ampicillin/sulbactam (iv) (then amoxicillin/clavulanate [po]) Ampicillin/sulbactam (iv) Ampicillin/sulbactam (iv) Ampicillin/sulbactam (iv) Ampicillin/sulbactam (iv) and/or amoxicillin/clavulanate (po) Amoxicillin/clavulanate (iv/po) Ticarcillin/clavulanate (iv) Ticarcillin/clavulanate (iv) Piperacillin/tazobactam (iv) Piperacillin/tazobactam (iv/im) Piperacillin/tazobactam (iv) Fluoroquinolones Ciprofloxacin (po) Ciprofloxacin (iv. noncomparative Prospective noncomparative RDBCT subgroup a Prospective. No. observational 48 94 22 33 RDBCT Uncontrolled. then po) Ciprofloxacin (po) and clindamycin (po) Study design Patient group Type/severity of infection(s) Reference 8 23 60 18 12 13 20 23 29 90 53 Prospective.Table 7. noncomparative RDBCT subgroup a Prospective. then po) Ofloxacin. noncomparative Randomized. randomized doses Prospective. and was then discharged home Hospitalized initially Outpatients Moderate Complicated soft-tissue Complicated soft-tissue Moderate-to-severe Parenteral. noncomparative RDBCT RCT Hospitalized Hospitalized Hospitalized Outpatient or hospitalized Limb-threatening Moderate-to-severe Mild-to-severe All types [147] [148] [142] [121] 191 28 17 29 38 34 46 43 120 Observational. observational RCT Hospitalized Hospitalized Hospitalized Hospitalized Hospitalized Hospitalized Hospitalized Hospitalized Outpatient Hospitalized Hospitalized initially Presumptive anaerobic Moderate-to-severe Failing to respond to therapy Mild-to-severe Mixed Mixed PVD. noncomparative RCT subgroup RCT subgroup a a Mostly hospitalized Inpatient or outpatient Hospitalized Hospitalized Outpatient Hospitalized Hospitalized Hospitalized Hospitalized initially.

many centers have reported successful use of femoral-distal bypass procedures in diabetic patients [186–189]. but a discussion of these is beyond our scope. which are less definitive and controllable and may require prolonged and repeated applications (B-III) [194. Two adjunctive modalities do deserve brief comments. controlled trial (each arm is listed separately in the table).Table 7. or separately identifiable as diabetic patients with foot infections. peripheral vascular disease. 201]. RDBCT. or tissue nippers is generally preferable to hydrotherapy or topical debriding agents. (Continued. within 1–2 days). staged procedures [191]. predominantly. Many types of devices can off-load the infected wound. 190]. double-blinded. 23. A preliminary meta-analysis of these trials suggests that G-CSF does not accelerate resolution of infection but may significantly reduce the need for operative procedures (B-I) [228]. antimicrobial dressings [217–219]. but it is important to choose one that permits easy inspection [202]. including wound vacuum-drainage systems [203–206]. 235] and inflamGuidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 897 . for infected wounds. thereby enabling wound healing and removing a reservoir of potential pathogens [82. 192–194]. Adjunctive treatments. Optimal surgical management may require multiple.e. Removal of pressure from a foot wound (i. Formulate a wound-care plan. The goal is to physically excise dead and unhealthy tissue. 196–199].e. Investigators and industry repre- sentatives have advocated many types of wound-care treatments. Although each treatment likely has some appropriate indications. scissors. 195].. recombinant growth factors [207–212]. for whom. Second.. PVD. Any experienced clinician may perform limited debridement. 213–216]. and with what protocols these expensive and limited resources might be used in the treatment of diabetic foot infections. several anecdotal and retrospective reports suggest that hyperbaric oxygen therapy may be of value for treatment of diabetic foot wounds. The primary indicators of improvement are resolution of local and systemic symptoms and clinical signs of inflammation. especially for a neuropathic foot. Only additional randomized clinical trials can establish when. available evidence is insufficient to recommend routine use of any of these modalities for treatment or prophylaxis. On the other hand. and a few recent prospective studies have shown promising results [229–232]. of treated patients Type/severity of infection(s) Antibiotic (route) Miscellaneous agents Aztreonam (iv) Clindamycin (po) Piperacillin/clindamycin (iv) Pexiganan (topical) Linezolid (iv or po) Daptomycin (iv) Study design a Patient group Reference 20 29 24 415 241 50 Prospective subgroup RDBCT Randomized. RCT. granulocyte colony-stimulating factors (G-CSFs) have now been investigated in 5 randomized trials involving diabetic foot infections [223–227]. First. The wound may require additional attention after the debridement performed during the initial assessment (table 4). severe soft-tissue Mild-to-moderate Wagner grade 2–4 wounds Mild-to-moderate infected ulcers All types Complicated skin [162] [84] [160] [130] [121] [163] NOTE. A recent Cochrane review concluded that hyperbaric oxygen therapy significantly reduced the risk of major amputation related to a diabetic foot ulcer [233] (B-I). For a patient with a severely infected ischemic foot. FOLLOW-UP Careful observation of the patient’s response to therapy (figure 4) is essential and should be performed daily for inpatients and perhaps every 2–5 days initially for outpatients (B-III). Neither should be used as a substitute for proper surgical debridement and conventional therapy. The infected wound should be dressed in a manner that allows daily inspection and encourages a moist wound-healing environment (B-III). This can usually be undertaken as a clinic or bedside procedure and without anesthesia. careful debridement of necrotic infected material should not be delayed while awaiting revascularization. including WBC counts [234. it is usually preferable to perform any needed revascularization early after recognizing the infection (i. a Involved patients with diabetic foot infections who constituted an identified subgroup of a larger trial of skin and skin structure infections. No evidence favors any particular type of dressing. rather than to delay this procedure in favor of prolonged (and potentially ineffective) antibiotic therapy (B-II) [123. convenience and cost are important considerations. randomized controlled trial. comparative RDBCT RCT RCT subgroup a Hospitalized Outpatient Hospitalized Outpatient Outpatient or hospitalized Hospitalized Acute. off-loading) is crucial to the healing process (AI) [200.) No. Blood test findings. Sharp debridement with scalpel. randomized. and the subjects were exclusively. There are many wound-care products that are touted as being able to improve healing in various ways [17. The clinical and microbiological outcomes were not consistently defined or routinely provided. Trials are those in which the purpose of the study was to examine the efficacy of antibiotic therapy. skin substitutes [203. open. procedure. and maggot (sterile larvae) therapy [220–222]. For more-severe vascular disease of the foot.

Inspect the site to ensure that the infection is responding and that the wound is healing.. Suggested empirical antibiotic regimens.Table 8. Determine the effectiveness of. and the initial clinical response (C-III). for diabetic foot infections. less-virulent bacteria (e.. as well as the clinical response to the empirical regimen. More virulent species (e. such as the erythrocyte sedimentation rate [122. aureus infection is proven or likely. Review the culture and drug susceptibility results and inquire about any adverse effects related to the current antibiotic therapy.g. and the patient’s compliance with. Evaluate glycemic control. 1. Mild Oral for most Moderate Oral or parenteral. a superinfection. an undiagnosed deep abscess or case of osteomyelitis. For a clinically stable patient who has had у1 unsuccessful courses of therapy. aureus and group A or B streptococci) should always be covered. con- sider discontinuing antimicrobials for a few days and then collecting optimal specimens for culture (C-III). Ensure that blood glucose levels and other aspects of the patient’s metabolic status are adequately controlled. If clinical evidence of infection persists beyond the expected duration.g. based on clinical severity. It is not always necessary to cover all microorganisms isolated from cultures. No evidence supports giving antibiotics for the entire time that the wound remains open. 237] and the C-reactive protein level [238]. 2. Choose a definitive antibiotic regimen (including the treatment duration) on the basis of the results of cultures. the prescribed regimens. reassess the need for surgical intervention. Suggest (or seek consultation for) alternatives when necessary. check on the patient’s compliance with antibiotics and re-evaluate for unaddressed adverse biological factors (figure 3). matory markers. 236. or ischemia that is more severe than was initially suspected. Review the off-loading and wound care regimens. and only linezolid is currently specifically approved for diabetic foot infections. If neither is occurring. imaging. . Select the definitive antibiotic regimen. Similar agents of the same drug class may be substituted. Re-evaluate the wound. These may include the development of antibiotic resistance. Antibiotics should be used for a period defined by the biology of the infection and by the clinical syndrome. a For patients in whom methicillin-resistant S. select agents with activity against all isolates. as suggested in table 9 (A-II). coagulase-negative staphylococci and enterococci) may be less important (B-II). and 4). S. or other investigations. 2. although is it reassuring to see elevated levels decrease and cause for concern when they do not. Definitive regimens should consider results of culture and susceptibility tests. but in a polymicrobial infection. If the infection has not responded to the empirical regimen. the clinician should accomplish 4 tasks (figures 1. are of limited use for monitoring response. based on clinical situation and agent(s) selected … … … Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes Yes … … Severe Intravenous. at least initially … … … … … … … … … … … … … … Yes Yes Yes Yes Route and agent(s) Advised route Dicloxacillin Clindamycin Cephalexin Trimethoprim-sulfamethoxazole Amoxicillin/clavulanate Levofloxacin Cefoxitin Ceftriaxone Ampicillin/sulbactam Linezolida (with or without aztreonam) Daptomycina (with or without aztreonam) Ertapenem Cefuroxime with or without metronidazole Ticarcillin/clavulanate Piperacillin/tazobactam Levofloxacin or ciprofloxacin with clindamycin Imipenem-cilastatin Vancomycina and ceftazidime (with or without metronidazole) Yes Yes Yes Yes Yes Yes … … … … … … … … … … … … NOTE. 898 • CID 2004:39 (1 October) • Lipsky et al. 3. When a hospitalized patient is ready for discharge or an outpatient returns for follow-up. Some of these regimens may not have US Food and Drug Administration approval for complicated skin and skin-structure infections. 4.

osteomyelitis impairs healing of the overlying wound and acts as a focus for recurrent infection. Algorithm 1. part 3: approach to assessing a diabetic patient with a foot infection who is not responding well to treatment. First among several problems is that the lack of a consensus definition of the disease hinders the comparison of available studies and experiences. transcutaneous partial pressure of O2. there are many available diagnostic tests. Any ulcer in which bone is either visible or can be easily palpated with a sterile blunt metal probe is likely to be complicated by osteomyelitis [83]. Finally.Figure 3. but the performance characteristics of this test have not yet been fully defined. and the required duration of antibiotic therapy [240]. but they often yield equivocal results. Furthermore. the presence of osteomyelitis increases the likelihood of surgical intervention. A swollen foot in a patient with a history of foot Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 899 . In patients with a limbthreatening infection. Suspect underlying osteomyelitis when an ulcer does not heal after at least 6 weeks of appropriate care and offloading. including amputation. especially one that is chronic or overlies a bony prominence (figure 5) [245]. OSTEOMYELITIS Dealing with osteomyelitis is perhaps the most difficult and controversial aspect in the management of diabetic foot infections [239–244]. TcPO2. When to consider the diagnosis. Next. Consider osteomyelitis as a potential complication of any deep or extensive ulcer. positive results of a probe-to-bone test may be taken as nearly sufficient for diagnosis.

.Figure 4. aureus. Confirming the diagnosis. swollen digit) [246].e. a red. Finally. a “sausage toe” (i. radiologically evident bone destruction beneath an ulcer should be considered to represent osteomyelitis unless proven otherwise [247]. Radioisotope scans are more sensitive than radiographs for detecting osteomyelitis during the early stages of this diseases. 251]. Because bony destruction is usually not seen on plain radiography performed during the early stages of disease and neuro-osteoarthropathy can mimic 900 • CID 2004:39 (1 October) • Lipsky et al. but the specificity of technetium bone scans is generally low [240. diagnosing osteomyelitis at the time the patient first presents to the hospital can be difficult [248–250]. MRSA. Algorithm 2: approach to selecting antibiotic therapy for a diabetic patient with a foot infection. methicillin-resistant Staphylococcus ulceration. but they are expensive and can be time-consuming [252].. infection. or an unexplained high WBC count [235] or inflammatory markers [236] should also arouse suspicion of osteomyelitis (B-II). Characteristic progressive changes on serial plain radiographs may help in more-chronic cases [247. The reported performance characteristics of various types of nuclear medicine scans varies.

may extend up to 4 weeks if slow to resolve 2–4 Weeks 2–4 Weeks Moderate Severe Bone or joint No residual infected tissue (e. 256–259].. Bone biopsy. If suspicion of osteomyelitis persists. setting. periosteal reaction. We found no published reports of complications of foot bone biopsy and consider it to be a safe procedure (B-II). 264] techniques) being a second choice. 270]. sending at least 1 for culture and another for histological analysis [269]. 2. Some physicians would also obtain biopsy specimens of most mid. interventional radiologist) can perform the biopsy. Provide antibiotic therapy for another 2–4 weeks and then perform radiograph again to determine whether bony changes have progressed (which would suggest infection). Empirical treatment. then consider oral switch Outpatient/inpatient Inpatient. If findings of radiography are only consistent with. With small toe bones. switch to oral when possible Parenteral or oral Parenteral or oral Initial parenteral. preferably after obtaining appropriate specimens for culture (B-III). The performance characteristics of all these diagnostic tests are highly correlated with the pretest probability of osteomyelitis. 262] or immunoglobulin [263. an orthopedic surgeon. 94. MRI is the most accurate imaging study for defining bone infection. 268. anesthesia may be unnecessary. If results of the imaging tests are negative.or hind-foot lesions. by clinical syndrome.g. of infection Soft-tissue only Mild Route of administration Topical or oral Setting for therapy Outpatient Duration of therapy 1–2 Weeks. Additional imaging studies. Unfortunately.Table 9. osteomyelitis is unlikely. above the ankle) amputation. osteomyelitis. If these radiographs show no evidence of pathological findings in bone. or residual dead bone postoperatively Oral (or initial parenteral) Initial parenteral. When osteomyelitis is a possibility. Various types of bone-cutting needles. then outpatient … … … … 2–5 Days 2–4 Weeks 4–6 Weeks 13 Months 253–255]. podiatrist. distributed by Propper and Sons) and Ostycut (Bard Products. Any properly trained physician (e. such as Jamshidi (Perfectum Corporation.g. but not characteristic of. MRI is usually not needed as a first-line investigation in cases of diabetic foot infection. 1. and if there is little likelihood of a noninfectious osteoarthropathy. Cultures of bone specimens provide more accurate microbiologic data than do those of soft-tissue specimens for patients with osteomyelitis [93. distributed by Angiomed) have been used. and mixed lucency and sclerosis). Obtain 2–3 specimens if possible. Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 901 . 265–268]. Percutaneous biopsy should preferably be done under fluoroscopic or CT guidance. with nuclear medicine scans (that preferably use newer generation leukocyte [239. traversing uninvolved skin if possible... If the initial films show classic changes suggestive of osteomyelitis (cortical erosion. 261. then consider oral switch Initial parenteral. as defined below. and durations of antibiotic therapy. Use an appropriate procedure. MRI is the most useful of the currently available imaging modalities (A-I) [90. 92. The criterion (gold) standard for diagnosing osteomyelitis is isolation of bacteria from a reliably obtained sample of bone (using measures to minimize contamination) concomitant with histological findings of inflammatory cells and osteonecrosis (B-II). it may only be possible to aspirate a few bony spicules. consider whether bone biopsy is needed (vide infra). perform plain radiography again 2–4 weeks later. Site. Suggested route.e. treat for presumptive osteomyelitis. and it also provides the most reliable image of deep soft-tissue infections. few of the studies that have evaluated diagnostic tests or have assessed treatment outcomes have used this standard. obtaining plain radiographs often suffices. For patients with sensory neuropathy. Collection of a sample of a bony lesion (either operatively or percutaneously) is recommended if the diagnosis remains in doubt after imaging or if osteomyelitis is likely but the etiologic agent or antibiotic susceptibilities are not predictable (B-II) [251. post-amputation) Residual infected soft tissue (but not bone) Residual infected (but viable) bone No surgery. one of the following choices should be considered. and they are most useful for intermediately probable cases [260]. MRI is the preferred imaging study. because these are more difficult to treat and more often lead to a high-level (i. 3. if results suggest osteomyelitis. by severity or extent. the patient should be treated for ∼2 weeks for the soft-tissue infection.

Unfortunately. such as ray and transmetatarsal amputations. preferably after antibiotic therapy has been stopped for 1–2 weeks (if safe to do so). Definitive surgical solutions to osteomyelitis. who may thus opt for attempts at medical management. Traditionally. or involcrum. Neuropathy and reduced systemic manifestations of infection may make osteomyelitis tolerable for the patient. Published reports on nonsurgical treatment with a prolonged (3–6 months) course of antibiotics have reported clinical success in ∼65%–80% of cases [155. 173. lucency and sclerosis. and a nonhealing wound. how patients were selected. By contrast. 237. also mask progressive bone destruction. sequestrum. whether patients were enrolled prospectively or . some have disputed the routine need for surgical resection [239]. resulting in altered biomechanics and additional cycles of ulceration. 271–276]. may risk architectural reorganization of the foot. additional bone or soft-tissue necrosis. 1Cortical erosion. periosteal reaction. Recently. these nonrandomized case series often fail to specify a definition of osteomyelitis. these diabetic complications may 902 • CID 2004:39 (1 October) • Lipsky et al. Algorithm 3: evaluating a diabetic patient who has suspected osteomyelitis of the foot. 243. 2May be done percutaneously or operatively. with delayed or inadequate surgery resulting in poorly controlled infection. 265]. authorities have believed that resecting a bone with chronic osteomyelitis was essential for cure [240. These arguments have led some health care professionals to treat diabetic foot osteomyelitis with little or no surgical intervention [239]. Choosing between medical and surgical therapy.Figure 5.

routes. cost-effective algorithm Guidelines for Diabetic Foot Infections • CID 2004:39 (1 October) • 903 .. There are 6 areas in which future research would be particularly helpful (A-III). Patients with severe neuropathy. and duration) for various types of soft-tissue and bone infections. performing daily self-examination of the feet. or critical ischemia should be referred to appropriate specialists to deal with these problems (A-II). Conducting systematic audits of outcomes and patient treatment processes may be useful for individual practitioners and for multidisciplinary foot-care teams (B-II). are important areas for future study. Educate the patient about the importance of optimizing glycemic control. Overall. Factors associated with a poor outcome include signs of systemic infection [237]. especially in those with osteomyelitis. and was it administered for a sufficient duration? Fourth. The patient has ischemia caused by unreconstructable vascular disease but desires to avoid amputation. or revascularization. avoiding foot trauma.g.. Establish a robust. usually in consultation with a knowledgeable surgeon. 121.even consecutively. A recent survey of members of the Emerging Infections Network found that the acceptable median failure rate for treating diabetic foot osteomyelitis was 18% [288]. especially if an agent with suboptimal bioavailability is used (C-III). 281. whereas others may elect long-term or intermittent antibiotic suppression or. using appropriate footwear at all times. First. making this a good time to reinforce preventive actions with the patient [11. clinicians should reinforce these preventive measures by questioning patients about foot care and regularly examining their feet and shoes. PREVENTION A patient who has had 1 foot infection is more likely to have another. hyperbaric oxygen therapy. The most appropriate duration of therapy for any type of diabetic foot infection has not been well defined [129]. 147. and how much nonoperative debridement of bone was performed. relapses may be difficult to differentiate from a reinfection. did the selected antibiotic regimen likely cover the causative organism(s) and achieve adequate levels in bone. When therapy for osteomyelitis fails. 283–285]. Detection of neuropathy before its complications ensue is the best method to prevent foot infections. radical cure of the infection would cause unacceptable loss of function). Selecting an antibiotic regimen. and there is minimal soft-tissue loss. 282]. RECOMMENDED RESEARCH Few of the recommendations in this guideline are based on properly designed and adequately powered randomized studies. 3. consider several issues. When a radical resection leaves no remaining infected tissue. osteomyelitis [273. Alternatively. there are 4 cases in which nonsurgical management of osteomyelitis might be considered (B-II). diagnosis. in some cases. expect a good clinical response (i. 2.e. Infection is confined to the forefoot. was the original diagnosis correct? Second. simple classification system for infected foot lesions to facilitate multicenter comparative studies of their natural history. OUTCOMES The goals of treating a diabetic foot infection are the eradication of clinical evidence of infection and the avoidance of soft-tissue loss and amputations. 4. and treatment. 289. 1. Because basic screening can be completed in a few minutes. is there residual necrotic or infected bone or surgical hardware that should be resected or removed? Third. and reporting any changes to health care professionals (A-II). amputation. if infected bone or soft tissue remain despite surgery. 283].e. Parenteral therapy may be delivered in the outpatient setting. as well as what duration of antibiotic therapy is needed. was the failure to eradicate bone infection the real cause of the current wound problem? Each case needs an individualized approach. 2. 1. where available [153. Determine optimal antibiotic regimens (agents. Relapses occur in ∼20%–30% of patients. and proximal location of the infection [287]. 130. embedded in beads or cement) [277–280]. continued prolonged treatment is necessary. 3. There is no acceptable surgical target (i. validated. Our recommendations for duration of therapy are based on the clinical syndrome and are summarized in table 9. 145. It is important to consider the presence and amount of any residual dead or infected bone and the state of the soft tissues. The determination of which patients are suitable for nonsurgical treatment. Selected patients may benefit from implanted antibiotics (e. substantial foot deformity. We support efforts to validate the International Consensus PEDIS system for foot-ulcer research purposes. minimal antibiotic therapy is needed (B-II). 4. Establish a consensus definition of osteomyelitis in the diabetic foot. 237. Determine whether there is a role for antibiotic therapy in managing clinically uninfected ulcers. For osteomyelitis.. Meanwhile. The patient and health care professional agree that surgical management carries excessive risk or is otherwise not appropriate or desirable. the presence of necrosis or gangrene [276]. resolution of clinical evidence of infection) to appropriate therapy in 80%–90% of mild-to-moderate infections [84. Design and validate a simple. an inexperienced surgeon [286]. some parenteral therapy may be beneficial. 5. inadequate limb perfusion. 263] and in 60%–80% of severe infections or cases of osteomyelitis [130. 290].

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