Version May 2024
INTRODUCTION — Diabetic foot infections are associated with substantial morbidity and mortality [1]. Important risk factors for development of diabetic foot infections include neuropathy, peripheral vascular disease, and poor glycemic control. In the setting of sensory neuropathy, there is diminished perception of pain and temperature; thus, many patients are slow to recognize the presence of an injury to their feet. Autonomic neuropathy can cause diminished sweat secretion resulting in dry, cracked skin that facilitates the entry of microorganisms to the deeper skin structures. In addition, motor neuropathy can lead to foot deformities, which lead to pressure-induced soft tissue damage. Peripheral artery disease can impair blood flow necessary for healing of ulcers and infections. Hyperglycemia impairs neutrophil function and reduces host defenses. Trauma in patients with one or more of these risk factors precipitates development of wounds that can be slow to heal and predispose to secondary infection.
The microbiology, clinical evaluation, diagnosis, and management of diabetic foot infections will be reviewed here. The general evaluation of the diabetic foot and management of uninfected diabetic foot lesions are discussed separately. (See "Evaluation of the diabetic foot" and "Management of diabetic foot ulcers".)
GUIDELINES — In 2012, the Infectious Disease Society of America updated guidelines on the diagnosis and management of diabetic foot infections, which were originally published in 2004 [2]. Practical guidelines are also published regularly by the International Working Group on the Diabetic Foot [3]. The information reviewed in this topic is largely consistent with these guidelines.
Links to these and other guidelines related to care of diabetes mellitus are found below. (See 'Society guideline links' below.)
MICROBIOLOGY — Most diabetic foot infections are polymicrobial, with up to five to seven different organisms isolated by culture. The microbiology of diabetic foot wounds is variable depending on the extent of involvement [4-8]:
●Superficial diabetic foot infections (including cellulitis and infected ulcers in antibiotic-naïve individuals) are likely due to aerobic gram-positive cocci (including Staphylococcus aureus, Streptococcus agalactiae, Streptococcus pyogenes, and coagulase-negative staphylococci).
●Ulcers that are deep, chronically infected, and/or previously treated with antibiotics are more likely to be polymicrobial. Such wounds may involve the above organisms in addition to enterococci, Enterobacteriaceae, Pseudomonas aeruginosa, and anaerobes.
●Wounds with extensive local inflammation, necrosis, malodorous drainage, or gangrene with signs of systemic toxicity should be presumed to have anaerobic organisms in addition to the above pathogens. Potential pathogens include anaerobic streptococci, Bacteroides species, and Clostridium species [9-13].
The typical microbiological spectrum also differs by geographic location, with gram-negative pathogens predominating in the sub-tropical climates of Africa and Asia, in contrast to the predominantly gram-positive organisms seen in the Western hemisphere [14,15].
Compared to culture results, advanced molecular tests (eg, 16S rRNA PCR or DNA sequencing) may detect more organisms (especially anaerobes) than cultures of samples from diabetic foot infections; however, the specificity of such advanced molecular testing is likely to be poor because the tests cannot differentiate true from commensal pathogens [16,17].
Risk of specific organisms — The likelihood of certain organisms should be considered when choosing empiric antibiotic therapy for diabetic foot infections. As explained below, certain microorganisms are known to be common pathogens in diabetic foot infections whereas others are likely to be copathogens as part of a polymicrobial infection [18].
Resistant Staphylococcus aureus — Methicillin-resistant S. aureus (MRSA) is a common pathogen in diabetic foot infections, particularly in those who have had previous MRSA infections or known colonization. Other risk factors for MRSA infection include prior antibiotic use, previous hospitalization, and residence in a long-term care facility. (See "Methicillin-resistant Staphylococcus aureus (MRSA) in adults: Epidemiology", section on 'Risk factors'.)
It is also important to note that diabetic patients with chronic foot wounds who receive repeated and prolonged courses of antibiotics represent an important risk group for development of vancomycin-intermediate S. aureus infections. (See "Staphylococcus aureus bacteremia with reduced susceptibility to vancomycin".)
Pseudomonas aeruginosa — P. aeruginosa is a particularly prevalent organism in diabetic foot infections reported from regions with warm climates. As an example, in a study of 434 patients with infected diabetic foot ulcers in Northern India, P. aeruginosa was the most common isolate, found in 20 percent of initial cultures [19]. Macerated ulcers, foot soaking, and other exposure to water or moist environments also likely increases the risk of involvement with P. aeruginosa.
However, in temperate climates and in the absence of the preceding findings and exposures, P. aeruginosa is a relatively uncommon pathogen [20]. In a study of 292 patients hospitalized with diabetic foot infections without osteomyelitis at five urban medical centers across the United States, the prevalence of P. aeruginosa was only 9 percent and was associated with immunocompromise or recent antibiotic exposure [21]. Furthermore, its role as a pathogen in routine clinical practice is often hard to assess. As an example, when P. aeruginosa was isolated from participants of clinical studies of diabetic foot infections, most patients improved on antibiotic regimens that did not cover Pseudomonas, suggesting that it was not the primary pathogenic organism [22,23].
Resistant enteric gram-negative rods — Gram-negative bacilli that express an extended-spectrum beta-lactamase (ESBL) are increasing in prevalence worldwide. These pathogens are more common in patients with prolonged hospital stays, prolonged catheterization, prior antibiotic use, or residence in a long-term care facility (see "Extended-spectrum beta-lactamases", section on 'Epidemiology'). The involvement of ESBL-producing organisms in diabetic foot infections in particular is also increasingly reported [24,25].
Anaerobic organisms — The role of anaerobes in diabetic foot infections remains unclear [7,10,26]. There is a lack of standard collection, transportation, and culture techniques amongst studies; however, some have found a high prevalence of anaerobes in samples taken from diabetic foot infections. Infections that are associated with malodorous drainage or are necrotic, deep, or severe are more likely to grow anaerobes. Whether the anaerobic organisms are truly pathogens remains unclear. Empiric antibiotic regimens for moderate to severe infections include anaerobic coverage.
CLINICAL MANIFESTATIONS
Spectrum of involvement — Diabetic foot infections can develop as a result of neuropathic or ischemic ulcers, traumatic wounds, skin cracks or fissures, or other defects in the skin of the foot or nail beds (paronychia) [2,27]. Thus, infection can present as localized superficial skin involvement at the site of a preexisting lesion or as infection of the skin or deeper skin structures that has spread beyond the site of local trauma. Such infections can subsequently extend to joints, bones, and the systemic circulation [28].
Skin and soft tissue infection — Diabetic foot infections are often accompanied by the cardinal manifestations of inflammation (erythema, warmth, swelling, and tenderness) and/or the presence of pus in an ulcer or sinus tract [4]. However, these local signs of infection may not be evident in all cases. Infections may not manifest with warmth and erythema in the setting of severe peripheral vascular disease. Diabetic patients with sensory neuropathy may have diminished sensation in the involved area and therefore may not complain of tenderness nor, in some cases, even realize that infection is present. In such instances, infection may progress to involve deeper tissues before the patient seeks clinical attention.
Other local signs that may be present in diabetic foot infections are nonspecific and include nonpurulent drainage, friable or discolored granulation tissue, and undermining of wound edges [2].
Cutaneous bullae, soft tissue gas, skin discoloration, or a foul odor may occur in necrotizing infections. Findings of gangrene, severe ischemia, or tissue necrosis may denote the presence of a limb-threatening infection.
Systemic signs such as fever, chills, hypotension, and tachycardia may accompany local signs of infection, and their presence indicates an increased severity of infection. (See 'Determining severity of infection' below.)
Osteomyelitis — Osteomyelitis can occur in the setting of a diabetic foot wound with or without evidence of local soft tissue infection. Clinical features associated with underlying osteomyelitis in patients with diabetic foot ulcers include the presence of a sinus tract, ulcer size >2 cm2, and depth allowing visibly exposed bone or ability to probe to bone [29-32]. The reliability of the "probe-to-bone test" in the setting of diabetic foot ulcers may vary by the ulcer location and the expertise of the clinician performing the test [33,34]. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Probing to bone'.)
The presence of a "sausage" toe, with erythema and nonpitting edema that obliterates the normal contour of the digit, has also been associated with underlying osteomyelitis in patients with diabetes, but the frequency of this finding is not known [35].
Although not specific or highly sensitive, the erythrocyte sedimentation rate (ESR) may be useful in evaluating whether osteomyelitis is present. The finding of an ESR of 70 or greater increases the clinical probability that osteomyelitis is present [31].
On plain radiographs, findings characteristic of osteomyelitis include cortical erosion, periosteal reaction, mixed lucency, and sclerosis [2,31]. There is often also evidence of soft tissue swelling. However, radiographs may be normal or have only subtle non-specific findings early in infection. Magnetic resonance imaging (MRI) findings of osteomyelitis include cortical destruction, bone marrow edema, and soft tissue inflammation. (See "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis", section on 'Conventional radiography' and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis", section on 'Magnetic resonance imaging'.)
DIAGNOSIS
Evaluation — The evaluation of a patient with a suspected diabetic foot infection involves three key steps: 1) determining the extent and severity of infection, 2) identifying underlying factors that predispose to and promote infection, and 3) assessing the microbial etiology.
The clinical history should focus on the details related to recent trauma, the duration of the current lesion(s), associated systemic symptoms, and prior treatment, if any. Mechanical factors that may predispose to the formation of an ulcer should be noted, and the history of blood glucose control should be assessed. Evidence of systemic toxicity should also be carefully sought.
Clinical examination should note the location of the lesions, extent of infection (eg, involving skin, subcutaneous tissue, muscles, tendons and/or bone) and whether bone is grossly visible or palpable by probing. Although osteomyelitis is highly likely if bone is visible, osteomyelitis may be present in the absence of such findings. (See 'Diagnosis of underlying osteomyelitis' below.)
Clinical examination should also include a neurologic evaluation that documents the extent of sensory loss as well as a vascular evaluation of the presence and severity of arterial and/or venous insufficiency. (See "Evaluation of the diabetic foot".)
Laboratory evaluation should include complete blood count as well as measurement of blood glucose, electrolytes, and renal function. Baseline and subsequent inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can be useful for monitoring response to therapy [6]. Some but not all studies have suggested that procalcitonin (PCT), a novel inflammatory marker, may also be useful if laboratory facilities that offer this test are locally available; further investigation is needed to determine the clinical utility of this assay [36]. (See 'Diagnosis of underlying osteomyelitis' below.)
Initial evaluation should include conventional radiographs to evaluate for bony deformity, foreign bodies, and gas in the soft tissue. In select cases, magnetic resonance imaging (MRI) can be performed to better evaluate for soft tissue abnormalities and osteomyelitis. (See 'Osteomyelitis' above and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)
If purulent drainage is present, samples for Gram stain and culture are appropriate. Aerobic and anaerobic cultures of deep tissue or bone biopsies should be obtained at the time of debridement if deep tissue infection or osteomyelitis is suspected. (See 'Obtaining samples for culture' below.)
If surgical intervention is warranted for management of infection, formal neurological and/or vascular evaluation is important for determining the extent of surgical intervention. (See 'Surgery' below and "Evaluation of the diabetic foot".)
Diagnosis of soft tissue infection — The diagnosis of a diabetic foot soft tissue infection is primarily based on suggestive clinical manifestations. The diagnosis is supported by presence of two or more features of inflammation (erythema, warmth, tenderness, swelling, induration, and purulent secretions) [2,37] (see 'Clinical manifestations' above). Microbial growth from a wound culture in the absence of supportive clinical findings is not sufficient to make the diagnosis of infection or to guide antibiotic therapy, since diabetic foot wounds are often colonized by bacteria [2,37]. (See 'Obtaining samples for culture' below.)
Alternative etiologies including osteomyelitis and acute diabetic neuroarthropathy (acute Charcot arthropathy) should be considered before a soft tissue infection may be presumed. (See 'Diagnosis of underlying osteomyelitis' below and 'Differential diagnosis' below.)
Diagnosis of underlying osteomyelitis — The possibility of osteomyelitis should be considered in diabetic patients with foot wounds associated with signs of infection in the deeper soft tissues and in patients with chronic ulcers, particularly those overlying bony prominences that do not heal after several weeks of wound care and off-loading. The diagnosis of osteomyelitis is definitively made through isolation of bacteria from a sterilely obtained bone biopsy sample with histologic evidence of inflammation and osteonecrosis [2,37].
In a meta-analysis including 11 cohort studies, 780 patients and 837 percutaneous bone biopsies (PBBs), the range of culture-positive PBBs in patients with suspected diabetic foot osteomyelitis was 56 to 99 percent; the pooled proportion with a positive culture was 84 percent (95% CI 73-91 percent) [38]. However, this meta-analysis did not allow assessment of the clinical utility of PBB or its effect on treatment success.
Beyond confirming a diagnosis of osteomyelitis, bone biopsies and cultures (and deep soft tissue cultures) can provide invaluable information to help guide antibiotic therapy. In a study of 305 patients with diabetic foot infection and osteomyelitis, culture results altered antibiotic selection in 87 percent of patients; regimens were narrowed in 62 percent and were broadened in 9 percent, and MRSA coverage was often discontinued [39].
However, bone biopsy is not always routinely available or practical. Furthermore, bone cultures may be negative in patients who have already received antibiotics, and bone histology may not show inflammation due to sampling error. In such instances, the presumptive diagnosis is based on clinical and radiographic assessment.
Certain clinical findings can support the diagnosis of osteomyelitis. In two systematic reviews that evaluated the diagnostic accuracy of exam findings in the setting of diabetic foot ulcers, the following factors increase the likelihood of osteomyelitis [31,32]:
●Grossly visible bone or ability to probe to bone (see "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Probing to bone')
●Ulcer size larger than 2 cm2
●Ulcer duration longer than one to two weeks
●Erythrocyte sedimentation rate (ESR) >70 mm/hour
If bone is grossly visible, supportive radiographic findings may not be necessary to make a diagnosis of osteomyelitis. However, for diabetic patients with one or more of the other above factors, a conventional radiograph with consistent changes can be helpful in making the diagnosis of osteomyelitis and providing a baseline image useful for subsequent management decisions. If the radiograph is indeterminate or normal and the diagnosis remains uncertain, such patients should undergo magnetic resonance imaging (MRI), which is highly sensitive and specific for osteomyelitis and superior to radiographs, three-phase bone scans, and white blood cell scans [2,31,32,37,40]. MRI is generally unnecessary if the plain radiograph is consistent with osteomyelitis; however, MRI can be helpful if there is remaining concern for an abscess or to guide surgical intervention. (See 'Osteomyelitis' above.)
In cases of diagnostic uncertainty based on clinical or radiographic features, failure of empiric antibiotic therapy, planned hardware placement in potentially infected bone, and mid- or hindfoot lesions that could lead to high-level amputations if inadequately treated, obtaining a bone sample to establish diagnosis is recommended [2]. Culture of such bone biopsy specimens is also important for identifying the causative organisms and their susceptibilities in order to guide antimicrobial therapy. (See 'Obtaining samples for culture' below.)
A detailed approach to the diagnosis of osteomyelitis in general is outlined separately. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis" and "Approach to imaging modalities in the setting of suspected nonvertebral osteomyelitis".)
Determining severity of infection — Assessment of the severity of diabetic foot infections is important for prognosis and to assist with management decisions (eg, need for hospitalization, surgical evaluation, or parenteral versus oral antibiotic therapy).
There are multiple different classification and scoring systems for diabetic foot infections [41].
In 2004, the Infectious Diseases Society of America (IDSA) published guidelines on the diagnosis and treatment of diabetic foot infections outlining a clinical classification scheme to define levels of severity (table 1) [6]. It classifies diabetic foot changes as uninfected, mild, moderate, and severe based on the extent of inflammatory findings, the tissue depth involved, and the presence of signs of systemic toxicity. The International Working Group on the Diabetic Foot (IWGDF) published a nearly identical classification system [37]. Prognostic evaluation of these classification schemes reveals that increasing infection severity is associated with a trend toward increased amputation risk, higher level amputations, and increased hospitalizations [42,43]. Patients classified as having osteomyelitis typically require more extensive management and have poorer outcomes; in 2019, the IWGDF revised their classification scheme to include whether osteomyelitis is present in moderate or severe infections [44].
Pending further studies to validate revised classification systems, we continue to use either the IDSA classification (and we note whether the patient has osteomyelitis) or the 2019 IWGDF classification.
DIFFERENTIAL DIAGNOSIS — Other processes that lead to inflammatory changes in the skin of the lower extremities can mimic an infection.
These include:
●Charcot arthropathy − Onset of Charcot arthropathy may be acute or subacute. Patients characteristically present with sudden onset of unilateral warmth, redness, and edema over the foot or ankle, often with history of minor trauma [45]. The affected foot may be discernably warmer than the contralateral foot. Alternatively, in some cases, patients present with a slowly progressing arthropathy with insidious onset of swelling over months or years. Occasionally, recurrent acute attacks may occur. The most frequently involved joints are the tarsus and tarsometatarsal joints, followed by the metatarsophalangeal joints and the ankle [46,47]. (See "Diabetic neuroarthropathy".)
●Venous stasis. (See "Clinical manifestations of lower extremity chronic venous disease".)
●Deep vein thrombosis. (See "Clinical presentation and diagnosis of the nonpregnant adult with suspected deep vein thrombosis of the lower extremity".)
●Crystal-associated arthritis. (See "Clinical manifestations and diagnosis of gout" and "Clinical manifestations and diagnosis of calcium pyrophosphate crystal deposition (CPPD) disease".)
●Fracture and other trauma-associated injuries. (See "Evaluation, diagnosis, and select management of common causes of forefoot pain in adults".)
Usually, these can be distinguished from infection based on clinical history, physical exam, and imaging findings. However, infection may coexist with other processes, and empiric antimicrobial therapy may be warranted in some cases when the diagnosis is uncertain.
MANAGEMENT — Management of diabetic foot infections requires attentive wound management, good nutrition, appropriate antimicrobial therapy, glycemic control, and fluid and electrolyte balance. Although severe infections (table 1) warrant hospitalization for urgent surgical consultation, antimicrobial administration, and medical stabilization, most mild infections and many moderate infections can be managed in the outpatient setting with close follow-up [10,23]. Hospitalization may be needed for mild or moderate infections if the patient cannot manage glycemic control at home, is unable to obtain or comply with proper wound care or offloading, needs parenteral antibiotics and is unsuitable for outpatient parenteral antimicrobial therapy, or needs more urgent diagnostic studies or surgical consultation [10,23].
Several studies have reported improved outcomes with a multidisciplinary approach to diabetic foot infections. This includes involvement of specialists in wound care, infectious diseases, endocrinology, and surgery [2,48-50].
Wound management — Local wound care for diabetic foot infections typically includes debridement of callus and necrotic tissue, wound cleansing, and relief of pressure on the ulcer [2,37].
Sharp debridement, with the use of a scalpel or scissors to shear off necrotic tissue, is the preferred method to remove callus and nonviable tissue. Such debridement promotes wound healing and removes pathogens that are present in nonviable tissues [2]. However, enzymatic debridement may be preferable in patients with significant vascular compromise that might impede the ability to heal new wounds created by sharp debridement [51]. As a general rule, surgical intervention is needed for patients with extensive infection of subcutaneous or deeper structures. (See "Management of diabetic foot ulcers", section on 'Debridement' and 'Surgery' below.)
The purpose of wound dressing is to absorb exudate and create a moist environment to promote healing. A wide array of dressing and wound healing products for ulcer management are available. These products include enzymes, gels, hydrocolloids, honey and antiseptics containing iodine or silver salts. However, the efficacy of these agents has not been evaluated or compared in carefully designed studies [27,52]. Avoidance of weight bearing is generally more important than the specific type of wound dressing or ointment applied. (See "Management of diabetic foot ulcers", section on 'Dressings'.)
Off-loading the pressure on the diabetic foot wound is essential to wound care. Various devices to relieve pressure on the foot are available, including casts and special shoes. The choice of device should be based on the wound location, the severity of infection, and the presence of peripheral arterial disease. (See "Management of diabetic foot ulcers", section on 'Mechanical offloading'.)
Obtaining samples for culture — Because microorganisms often colonize lower extremity wounds regardless of the presence of a true infection, cultures should be performed only in selected patients. If the clinical suspicion for infection is low, samples from the wound should not be submitted for culture. In patients with mild infection (table 1) in whom there is low suspicion for resistant organisms (eg, no recent antibiotic course), wound culture is often not necessary. However, wound culture is often helpful in cases of moderate or severe infection (table 1) and when the concern for multidrug-resistant organisms is high. Ideally, samples for culture should be obtained prior to the initiation of empiric antibiotics. However, in cases of systemic toxicity or limb-threatening infections, antibiotic therapy should not be withheld before surgical cultures are obtained.
The preferred clinical specimens for reliable culture include aspirate from an abscess or curettage from the ulcer base following superficial debridement of necrotic tissue. Organisms cultured from superficial swabs are not reliable for predicting the pathogens responsible for deeper infection [53-56]. (See "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis".)
In the setting of osteomyelitis, bone biopsy is the preferred method of sample collection for culture. If performed percutaneously, sampling through uninvolved tissue under radiographic guidance is preferred. Although sinus tract cultures may be of some use for prediction of osteomyelitis if S. aureus or Salmonella species are identified, in general, such cultures are not worthwhile [57,58]. (See 'Diagnosis of underlying osteomyelitis' above and "Nonvertebral osteomyelitis in adults: Clinical manifestations and diagnosis", section on 'Bone biopsy'.)
Samples should be sent for Gram stain and both aerobic and anaerobic bacterial cultures.
Surgery — Consultation with a surgeon with experience in diabetic foot infections is important for cases of severe infections and in most cases of moderate infections. Surgical debridement is required for cure of infections complicated by abscess, extensive bone or joint involvement, crepitus, necrosis, gangrene or necrotizing fasciitis and is important for source control in patients with severe sepsis [2,59,60]. The utility of early surgical debridement was illustrated in a retrospective review of 112 diabetic patients with severe foot infections [59]. Those patients who underwent surgical intervention at the time of presentation had a significantly lower rate of above-ankle amputation than those who received three days of intravenous antimicrobial therapy prior to surgery.
In addition to surgical debridement, revascularization (via angioplasty or bypass grafting) and/or amputation may be necessary. Determination of the extent of surgical intervention required should be guided by vascular evaluation [2,27]. (See "Lower extremity amputation", section on 'Indications for amputation' and "Techniques for lower extremity amputation" and "Management of diabetic foot ulcers", section on 'Ischemia and revascularization'.)
Antimicrobial therapy — Empiric antibiotic therapy should be selected based on the severity of infection and the likelihood of involvement of resistant organisms. (See 'Determining severity of infection' above and 'Microbiology' above.)
Subsequent antibiotic therapy should be tailored to culture and susceptibility results. However, it is not always necessary to cover all microorganisms isolated from cultures [6].
Patients with ulcerations that are not infected should not receive antibiotic therapy [61,62]. However, such patients often benefit from local wound care and measures that reduce the pressure at the site of ulceration.
Our treatment approach outlined below is consistent with the Infectious Diseases Society of America (IDSA) guidelines on the diagnosis and treatment of diabetic foot infections and is based on their classification scheme for severity of infection (table 1) [2,6]. (See 'Determining severity of infection' above.)
In general, the limited data on antibiotic therapy of diabetic foot infections do not allow comparison of outcomes of different regimens [2,37]. On the basis of the available observational studies and randomized trials, no single drug or combination appears to be superior to others [63-65]. In a systematic review of 12 studies comparing antibiotic regimens for lower extremity skin and soft-tissue infections in diabetic patients, reported clinical cure rates ranged from 48 to 90 percent [64]. None of the studies demonstrated a significant benefit for any specific antibiotic agent. However, subsequent data suggest that tigecycline, specifically, may not be as effective as other regimens; it resulted in lower clinical cure rates and did not meet prespecified non-inferiority criteria compared with ertapenem with or without vancomycin in a randomized, double-blind trial of patients with diabetic foot infections [66].
Empiric therapy
Mild infection — Mild diabetic foot infections can be treated with outpatient oral antimicrobial therapy. Empiric therapy of patients with mild infections should include activity against skin flora including streptococci and S. aureus. Agents with activity against methicillin-resistant S. aureus (MRSA) should be used in patients with purulent infections and those at risk for MRSA infection (see 'Resistant Staphylococcus aureus' above). Appropriate agents are outlined in the table (table 2).
We typically follow such patients for about a week. By that time, patients who have failed to respond to treatment with agents active against streptococci and methicillin-susceptible S. aureus should receive extended antimicrobial coverage to include activity against MRSA, aerobic gram-negative bacilli, and anaerobes (table 2).
Moderate infection — Empiric therapy of deep ulcers with extension to fascia should include activity against streptococci, S. aureus (and MRSA if risk factors are present), aerobic gram-negative bacilli and anaerobes and can be administered orally in many cases. Appropriate regimens are outlined in the table (table 2). Patients presenting with extensive infections that involve deep tissues or bone should receive empiric parenteral therapy with activity against the above pathogens (table 3). Empiric coverage for P. aeruginosa may not always be necessary unless the patient has particular risk for involvement with this organism, such as a macerated wound or one with significant water exposure. (See 'Pseudomonas aeruginosa' above.)
Severe infection — Limb-threatening diabetic foot infections and those that are associated with systemic toxicity should be treated with broad-spectrum parenteral antibiotic therapy. In most cases, surgical debridement is also necessary. Empiric therapy should include activity against streptococci, MRSA, aerobic gram-negative bacilli, and anaerobes. Appropriate regimens are outlined in the table (table 3) [67].
Targeted therapy — If appropriate wound cultures were submitted, antimicrobial therapy should be tailored to culture and susceptibility results when available. However, it is not always necessary to cover all microorganisms isolated from cultures [2,37]. Virulent species such as S. aureus and streptococci (group A or B) should always be covered, but in polymicrobial infections, less virulent organisms (such as coagulase negative staphylococci and enterococci) may be less important. Furthermore, if isolates are resistant to an empiric regimen to which the patient is clearly responding well, broadening the spectrum to include those isolates may not be necessary. On the other hand, if the patient is not responding, expanding therapy to target all isolated organisms may be warranted.
For those patients who were initiated on parenteral therapy, a switch to an oral regimen is reasonable following clinical improvement.
Duration of therapy — The duration of antibiotic therapy should be tailored to individual clinical circumstances. Patients with mild infection should receive oral antibiotic therapy in conjunction with attentive wound care until there is evidence that the infection has resolved (usually about one to two weeks). Antibiotics need not be administered for the entire duration that the wound remains open [2,37].
Patients with infection also requiring surgical debridement should receive intravenous antibiotic therapy perioperatively. In the absence of osteomyelitis, antibiotic therapy should be administered in conjunction with attentive wound care until signs of infection appear to have resolved (two to four weeks of therapy is usually sufficient). If there is a good response to parenteral therapy, oral agents can be used to complete the course of treatment [68]. A randomized study of 66 patients with diabetic foot infection without osteomyelitis found that 10 versus 20 days of antibiotics (intravenous followed by oral) given post-debridement did not affect clinical remission rates [69]. The results from this pilot study are being confirmed in a larger study.
Patients requiring amputation of the involved limb should receive intravenous antibiotic therapy perioperatively. If the entire area of infection is fully resected, a brief course of oral antibiotic therapy (less than a week) following surgery is usually sufficient [68].
Considerations for osteomyelitis — Similar to other types of diabetic foot infections, no data support the superiority of specific antimicrobial agents for osteomyelitis [64]. Appropriate regimens for empiric therapy are similar to those for moderate to severe diabetic foot infections (table 3).
Targeted antimicrobial therapy should be tailored to culture and sensitivity results, ideally from bone biopsy. In one retrospective study of diabetic patients with osteomyelitis of the toe or metatarsal head, remission (absence of signs of infection and no need for surgery after one year) was more likely in the 22 patients treated with regimens guided by bone biopsy data compared with the 28 treated based on swab culture data (82 versus 50 percent) [70]. Of note, those who had bone culture were also more likely to be treated with a rifampicin-containing regimen, which likely was a confounding variable and limits the interpretation of this finding. Directed antimicrobial therapy for osteomyelitis is discussed in detail elsewhere. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Definitive therapy'.)
Many patients with osteomyelitis of the foot benefit from surgical resection. In both a systematic review and meta-analysis of studies evaluating treatment of diabetic foot osteomyelitis, prolonged antibiotic therapy without resection had success rates comparable to those reported with surgery, with the caveat that the included studies were heterogeneous in how they defined osteomyelitis and treatment failure; there were no studies that directly compare surgical intervention to nonsurgical management [71,72].
Partial amputations of the foot (eg, ray or transmetatarsal amputations) may adversely alter the biomechanics of the foot, increasing the risk of future ulceration. Thus, in certain cases, limited surgical debridement combined with prolonged antibiotic therapy may be appropriate [2,37]. However, extensive surgical debridement or resection is preferable in the following clinical circumstances [2]:
●Persistent sepsis without an alternate source
●Inability to receive or tolerate appropriate antibiotic therapy
●Progressive bone deterioration despite appropriate antibiotic therapy
●Mechanics of the foot are compromised by extensive bony destruction requiring correction
●Surgery is needed to achieve soft tissue wound or primary closure
The duration of antibiotic therapy of osteomyelitis depends on the extent of residual affected tissue. This is discussed in detail elsewhere. (See "Nonvertebral osteomyelitis in adults: Treatment", section on 'Antibiotic therapy'.)
Adjunctive therapies — Adjunctive therapies for treatment of diabetic foot infections include vacuum-assisted wound closure, hyperbaric oxygen and granulocyte colony-stimulating factor (G-CSF) [73-75].
Of these, vacuum-assisted wound closure is used most frequently. In a randomized trial evaluating vacuum-assisted wound closure including 342 patients with diabetic foot ulcers, complete ulcer closure was achieved more often among those who used vacuum-assisted closure than those who did not (43 versus 29 percent, respectively) [73]. Vacuum-assisted closure and hyperbaric oxygen therapy are discussed in detail separately. (See "Management of diabetic foot ulcers" and "Hyperbaric oxygen therapy", section on 'Infection' and "Hyperbaric oxygen therapy", section on 'Nonhealing ulcers, skin grafts, and wound healing'.)
The role of G-CSF in managing diabetic foot infections is not clear. In a meta-analysis of five trials that included 167 patients, there was a reduction in the rates of surgical intervention and amputation, specifically, associated with the use of G-CSF (relative risks 0.38 [95% CI 0.21 to 0.70] and 0.41 [95% CI 0.18 to 0.95], respectively, compared with no G-CSF) and no significant difference in adverse effects [76]. There was no clear benefit to G-CSF with regards to infection resolution or improvement. The included studies were all of small size, and there was substantial clinical heterogeneity across studies, including variable antibiotic regimens used, G-CSF formulations and doses, and severity of underlying infection. Additional data are needed before G-CSF can be recommended or its high cost can be justified for use in diabetic foot infections.
Follow-up — Close follow-up is important to ensure continued improvement and to evaluate the need for modification of antimicrobial therapy, further imaging, or additional surgical intervention. Wound healing and a decrease in previously elevated inflammatory markers can be signs of clinical resolution and may be particularly helpful in cases of osteomyelitis. If clinical evidence of infection persists beyond the expected duration, issues of patient adherence to therapy, development of antibiotic resistance, an undiagnosed deeper infection (eg, abscess or osteomyelitis), or ischemia should be evaluated [6].
If infection in a clinically stable patient fails to respond to more than one antibiotic course, some favor discontinuing antimicrobial therapy for a few days (eg, 48 to 72 hours) in order to obtain a biopsy for culture off antibiotics and optimize the yield [6]. In general, this is a safe and reasonable approach, although deep cultures are often positive even if therapy is continued up to the time of debridement.
SOCIETY GUIDELINE LINKS — Links to society and government-sponsored guidelines from selected countries and regions around the world are provided separately. (See "Society guideline links: Diabetes mellitus in adults".)
INFORMATION FOR PATIENTS — UpToDate offers two types of patient education materials, "The Basics" and "Beyond the Basics." The Basics patient education pieces are written in plain language, at the 5th to 6th grade reading level, and they answer the four or five key questions a patient might have about a given condition. These articles are best for patients who want a general overview and who prefer short, easy-to-read materials. Beyond the Basics patient education pieces are longer, more sophisticated, and more detailed. These articles are written at the 10th to 12th grade reading level and are best for patients who want in-depth information and are comfortable with some medical jargon.
Here are the patient education articles that are relevant to this topic. We encourage you to print or e-mail these topics to your patients. (You can also locate patient education articles on a variety of subjects by searching on "patient info" and the keyword(s) of interest.)
●Basics topics (see "Patient education: Diabetes and infections (The Basics)")
SUMMARY AND RECOMMENDATIONS
●Pathogenesis – Hyperglycemia, sensory and autonomic neuropathy, and peripheral arterial disease all contribute to the pathogenesis of lower extremity infections in diabetic patients. These infections are associated with substantial morbidity and mortality. (See 'Introduction' above.)
●Clinical evaluation – Evaluation of a patient with a diabetic foot infection involves determining the extent and severity of infection through clinical and radiographic assessment, identifying and addressing underlying factors that predispose to and promote infection, assessing the microbial etiology, and determining the need for surgical intervention. (See 'Evaluation' above.)
●Diagnostic evaluation – Laboratory testing should include blood work to evaluate for leukocytosis as well as blood glucose, electrolytes, and renal function values so that glycemic control and acid base status can be evaluated and monitored. Baseline and subsequent inflammatory markers such as erythrocyte sedimentation rate (ESR) and C-reactive protein (CRP) can be useful for monitoring response to therapy. Conventional radiographs should be done to evaluate for bony and soft tissue deformity or abnormalities. Formal vascular evaluation is warranted in cases where peripheral arterial insufficiency is suspected. (See 'Evaluation' above.)
●Diagnosis – The presence of two or more features of inflammation (erythema, warmth, tenderness, swelling, induration, or purulent secretions) can establish the diagnosis of a diabetic foot infection. The definitive diagnosis of osteomyelitis is made through histologic and microbiologic evaluation of a bone biopsy sample. However, certain clinical factors can support the presumptive diagnosis of osteomyelitis in the absence of biopsy:
•Grossly visible bone or ability to probe to bone
•Ulcer size larger than 2 cm2
•Ulcer duration longer than one to two weeks
•ESR >70 mm/hour
Those with one or more of the above factors whose radiographs are normal or indeterminate for osteomyelitis should undergo magnetic resonance imaging (MRI). (See 'Diagnosis' above.)
●Microbiology – The microbiology of diabetic foot wounds varies with the severity and extent of involvement (table 1). Superficial infections are likely due to aerobic gram-positive cocci whereas deep, chronically infected, and/or previously treated ulcers are more likely to be polymicrobial. Anaerobic organisms may also be involved in wounds with extensive local inflammation, necrosis, or gangrene. When there is concern for multidrug-resistant organisms or in cases of moderate or severe infection (including deep infections and osteomyelitis), aerobic and anaerobic cultures of deep tissue or bone biopsies should be obtained at the time of debridement. Organisms cultured from superficial swabs are not reliable for predicting the pathogens responsible for deeper infection. (See 'Microbiology' above and 'Obtaining samples for culture' above.)
●Wound management – Management of diabetic foot infections requires attentive wound management, good nutrition, antimicrobial therapy, glycemic control, and fluid and electrolyte balance. Wound management includes attentive local wound care including debridement of callus and necrotic tissue, wound cleansing, and relief of pressure on the ulcer. Consultation with a surgeon with experience in diabetic foot infection is important for cases of severe infections and most cases of moderate infections. Prompt surgical debridement is critical for cure of infections complicated by abscess, extensive bone or joint involvement, crepitus, necrosis, gangrene, or necrotizing fasciitis and is important for source control in patients with severe sepsis. (See 'Wound management' above and 'Surgery' above.)
●Antibiotic selection – Empiric antibiotic therapy should be selected based upon the severity of infection and the likelihood of involvement of resistant organisms:
•Mild infections – For patients with mild infections, we suggest an empiric antimicrobial regimen (table 2) with activity against skin flora including streptococci and Staphylococcus aureus (including methicillin-resistant S. aureus [MRSA] if risk factors are present) (Grade 2C). (See 'Mild infection' above.)
•Deep ulcers – For patients with deep ulcers, we suggest an empiric antimicrobial regimen with activity against streptococci, S. aureus (and MRSA if risk factors are present), aerobic gram-negative bacilli, and anaerobes (Grade 2C). Oral antibiotics (table 2) may be appropriate for ulcers that extend to the fascia, whereas parenteral regimens (table 3) should be used for deeper infections. (See 'Moderate infection' above.)
•Limb-threatening infections or infections with systemic symptoms – For patients with limb-threatening diabetic foot infections or evidence of systemic toxicity, we suggest treatment with a broad-spectrum parenteral antibiotic regimen (table 3) with activity against streptococci, MRSA, aerobic gram-negative bacilli, and anaerobes (Grade 2C). (See 'Severe infection' above.)
Antimicrobial therapy should be tailored to culture and susceptibility results when available, and a switch to an oral from parenteral regimen is reasonable following clinical improvement.
●Monitoring – Close follow-up is important to ensure continued improvement and to evaluate the need for modification of antimicrobial therapy, further imaging, or additional surgical intervention. (See 'Targeted therapy' above and 'Duration of therapy' above and 'Follow-up' above.)
●Duration of antibiotic therapy – The duration of antibiotic therapy of osteomyelitis depends on the extent of residual affected tissue. Antibiotics need not be administered for the entire duration that the wound remains open. However, in certain cases, limited surgical debridement combined with prolonged antibiotic therapy may be appropriate. (See 'Considerations for osteomyelitis' above and "Nonvertebral osteomyelitis in adults: Treatment".)
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