Diabetic foot infections, including osteomyelitis: Treatment

INTRODUCTION — 

Management of diabetic foot infections is complex and requires a multidisciplinary approach. Treatment varies based on whether the infection is confined to soft tissue or osteomyelitis is present.

Antibiotics and surgical debridement are mainstays of therapy in patients with severe infections, and patients often require several weeks of antibiotic therapy along with prolonged wound care.

This topic discusses the management of diabetic foot infections, including both soft tissue infection and osteomyelitis. Clinical manifestations and diagnosis of diabetic foot infections are discussed in detail separately (see "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis"). Additionally, broad concepts of osteomyelitis treatment are discussed elsewhere. (See "Osteomyelitis in the absence of hardware: Approach to treatment in adults".)

Diabetic foot ulcers without infection are discussed separately. (See "Evaluation of the diabetic foot" and "Management of diabetic foot ulcers" and "Local care of diabetic foot ulcers".)

GENERAL APPROACH — 

Management of diabetic foot infections requires a multi-faceted approach, often involving clinicians from different specialties. Several studies have reported improved outcomes with a multidisciplinary approach that includes specialists in wound care, infectious diseases, endocrinology, and surgery [1-5].

Basic components of management include:

●Determining the severity of illness and initial site of care.

●Assessment for need of surgical and/or vascular intervention.

●Judicious and thoughtful use of antibiotics.

●Proper wound care, including offloading.

●Aggressive diabetes care.

●Management of predisposing conditions, such as peripheral neuropathy, peripheral artery disease, and edema [5].

Few controlled, randomized trials have been performed to guide management of diabetic foot infections. Treatment recommendations are often based on lower quality studies, expert opinion, and clinical experience. As such, most recommendations in expert guidelines are rated as having “low certainty” of evidence [5].

Our approach generally matches recommendations from the 2023 International Working Group on the Diabetic Foot (IWGDF) and Infectious Diseases Society of America (IDSA) expert guidelines [5].

DETERMINING SITE OF CARE — 

The patient’s severity of illness determines the need for hospitalization in most cases. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Classifying the infection'.)

Many patients with mild or moderate infections can be managed as outpatients with close follow-up [6,7].

Hospitalization is indicated if urgent surgical consultation, intravenous antibiotic administration, or medical stabilization is necessary [5]:

●Severe infection (ie, systemic sepsis). (See 'Classifying the severity of illness' below.)

●Focal findings concerning for serious infection [5-7]:

•Rapidly progressive or extensive erythema.

•Evidence of necrosis or necrotizing process, such as crepitus, gas on imaging, pain out of proportion to exam (pain may be absent in patients with diabetes due to neuropathy). (See "Necrotizing soft tissue infections", section on 'Clinical manifestations'.)

•Deep abscess.

•Severe foot ischemia.

●Inability to obtain or comply with proper wound care or offloading.

●Need for parenteral antibiotics that cannot be administered in the outpatient setting.

●Need for urgent diagnostic studies or surgical consultation for infection or foot ischemia.

Osteomyelitis is not an absolute indication for admission because many patients with bone infection are stable and can be treated with oral antibiotics or initiate intravenous therapy as an outpatient [5]. (See 'Oral versus intravenous route' below.)

SKIN AND SOFT TISSUE INFECTION WITHOUT OSTEOMYELITIS — 

Important components of management of skin and soft tissue diabetic foot infections are surgical consultation, antibiotic therapy, and wound management.

No role for treatment of colonized ulcers — Patients with diabetic foot ulcers that have no clinical evidence of infection should not receive antibiotic therapy. Positive wound cultures are not an indication for antibiotics since cultures of open wounds almost always grow organisms regardless of the presence or absence of infection. Treatment of ulcer colonization has not been shown to prevent infection and is associated with harmful side effects and potential development of resistant organisms [5,8-10].

Role of surgery — The primary role of surgery is to remove infected nonviable tissue (eg, necrotic tissue, abscess). Surgery also allows collection of deep tissue samples for culture.

Indications for surgery — All patients with severe soft tissue diabetic foot infection and most patients with moderate infection should be evaluated by a surgeon with experience in diabetic foot infections [5]. (See 'Classifying the severity of illness' below.)

Urgent surgical debridement is required for cure of infections with certain complications [1,11,12]:

●Deep or extensive abscess.

●Extensive bone or joint involvement. (See 'Indications for surgery' below.)

●Crepitus, necrosis, or gangrene.

●Necrotizing fasciitis.

●Severe lower extremity ischemia – Prior to surgery, vascular evaluation should be performed if there is concern for peripheral artery disease. Clinical exam may be unreliable, so noninvasive tests (eg, duplex ultrasound or ankle-brachial index tests) may be necessary. In some patients, revascularization (via angioplasty or bypass) is performed prior to surgical debridement because ischemia increases the likelihood of poor wound healing, treatment failure, and amputation (table 1) [1,13,14]. (See "Management of chronic limb-threatening ischemia".)

●Compartment syndrome.

In addition, patients with mild cellulitis surrounding a foot ulcer often require debridement if there is dead, necrotic, or callus tissue within and around the ulcer that can act as an ongoing nidus of infection [1,15]. Depending on the extent of involvement, this type of debridement can often be performed at the bedside.

Early surgery for severe diabetic foot infection decreases the risk of amputation [5,11,16,17]. The utility of early surgical debridement was illustrated in a retrospective review of 112 diabetic patients with severe foot infections [11]. Those patients who underwent surgical intervention at the time of presentation had a significantly lower rate of above-ankle amputation than those whose surgery occurred after 72 hours of intravenous antimicrobial therapy.

Surgical technique — Sharp debridement, with the use of a scalpel or scissors, is the preferred method to remove infected nonviable soft tissue. Such debridement promotes wound healing and removes pathogens that antibiotics cannot reach due to lack of blood supply to nonviable tissue.

Obtaining soft tissue cultures — To guide antibiotic selection, deep tissue samples should be obtained during surgery or bedside debridement for soft tissue infection. If possible, 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 samples from an abscess or curettage from the ulcer base following superficial debridement of necrotic tissue. Samples should be sent for Gram stain and both aerobic and anaerobic bacterial cultures.

Organisms cultured from superficial swabs are not reliable for predicting the pathogens responsible for deeper infection [18-21].

More detailed discussion of soft tissue cultures is found elsewhere. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Role of wound cultures'.)

Considerations prior to selecting antibiotics — Antibiotics for skin and soft tissue infection of the diabetic foot should be selected based on the severity of infection and the likelihood of involvement of resistant organisms.

Classifying the severity of illness — Severity of infection is classified as mild, moderate, or severe using the 2023 International Working Group on the Diabetic Foot (IWGDF) and Infectious Diseases Society of America (IDSA) scoring system (table 2) [5]. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Classifying the infection'.)

Indications for MRSA coverage — The need for coverage of methicillin-resistant Staphylococcus aureus (MRSA) is based on the patient’s underlying risk factors. In general, MRSA coverage is appropriate for patients with known MRSA colonization or prior infection. In certain regions, MRSA rates are high enough in patients with diabetes to consider empiric coverage; local epidemiology should be reviewed. Other risk factors, as seen in the table, may not be as strongly associated with MRSA infection, so we individualize the decision for MRSA coverage in such cases (table 3 and table 4 and algorithm 1). (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Resistant Staphylococcus aureus'.)

Indications for coverage of Pseudmonas — Routine empiric coverage for Psuedomonas aeruginosa is not necessary unless the patient has particular risk for infection with this organism, such as superficial skin necrosis with moist appearance and overlying pus, a wound with significant water exposure, or prolonged exposure to warm tropical or subtropical regions (algorithm 1 and table 4). We would also cover Pseudomonas if the patient grew this organism from an appropriately collected deep specimen in the setting of infection. We would not cover it if it grew from a superficial swab (unless other risk factors are present) or from a culture of an uninfected ulcer. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Pseudomonas aeruginosa'.)

Empiric antibiotic selection — In general, limited data on antibiotic therapy of diabetic foot infections do not allow for comparison of different regimens [1,5,15]. On the basis of the available observational studies and randomized trials, no single drug or combination appears to be superior to others [22-29]. In a systematic review of 12 studies comparing antibiotic regimens for lower extremity skin and soft-tissue infections in diabetic patients, none of the studies demonstrated a significant benefit for any specific antibiotic agent; reported clinical cure rates ranged from 48 to 90 percent [23].

Mild infection — Mild diabetic foot infections can be treated with outpatient oral antimicrobial therapy. For patients without recent antibiotic exposure, empiric therapy for mild infections should include activity against streptococci and S. aureus (algorithm 1). (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Common organisms'.)

Regimens primarily depend on risk factors for MRSA infection and are outlined in the algorithm (algorithm 1) (see 'Indications for MRSA coverage' above). Example regimens include:

●Without an indication for MRSA coverage – Dicloxacillin (500 mg orally every six hours), cephalexin (500 mg orally every six hours), or cefadroxil (500 mg orally twice daily).

●With an indication for MRSA coverage – Trimethoprim-sulfamethoxazole (TMP-SMX; one to two double-strength tablets orally twice daily, or amoxicillin (875 mg or 1000 mg orally twice daily) plus doxycycline (100 mg orally twice daily).

For patients who have had recent antibiotic exposure (eg, within four to six weeks), coverage of gram-negative bacilli, such as Escherichia coli, is reasonable (algorithm 1). Coverage for Pseudomonas spp is usually unnecessary for initial treatment of mild infections, but may be considered in patients unresponsive to initial therapy or who progress to more severe infection [5].

Moderate infection — Empiric therapy of moderate infection can be administered orally in many cases, and should include activity against streptococci, S. aureus (and MRSA if risk factors are present), aerobic gram-negative bacilli (including Pseudomonas spp if at risk), and anaerobes. (See 'Classifying the severity of illness' above and 'Indications for MRSA coverage' above and 'Indications for coverage of Pseudmonas' above.)

Specific oral regimens are outlined in the algorithm (algorithm 1), and example oral regimens are listed below:

●Without an indication for MRSA or Pseudomonas coverage – Amoxicillin-clavulanate (875 mg orally every 12 hours).

●With an indication for MRSA coverage – Amoxicillin-clavulanate (875 mg orally every 12 hours) plus either doxycycline (100 mg orally every 12 hours) or TMP-SMX (one to two double-strength tablets orally twice daily).

●With an indication for Pseudomonas coverage – Amoxicillin-clavulanate (875 mg orally every 12 hours) plus ciprofloxacin (750 mg orally every 12 hours).

●With an indication for MRSA and Pseudomonas coverage – Levofloxacin (750 mg orally once daily) plus metronidazole (500 mg orally every 8 to 12 hours) plus either doxycycline (100 mg orally every 12 hours), or TMP-SMX (one to two double-strength tablets orally twice daily).

Intravenous therapy should be considered in patients presenting with extensive infections that involve deep tissues. Specific regimens are outlined in the table (table 4).

Severe infection — Limb-threatening diabetic foot infections and those that are severe (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 (including Pseudomonas spp), and anaerobes (table 4).

Specific intravenous regimens are outlined in the table (table 4). An example regimen is vancomycin (see table for dosing (table 5)) plus piperacillin-tazobactam (4.5 g intravenously every six hours), or three-drug therapy with vancomycin, cefepime (2 g every eight hours), and metronidazole (500 mg intravenously every 8 to 12 hours).

Subsequent antibiotic selection — If an appropriately collected deep wound culture was submitted, antibiotic therapy should be tailored once culture and susceptibility results return (see "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Role of wound cultures'). However, it is not always necessary to cover all microorganisms isolated from cultures [5,8,15]. Virulent species such as S. aureus and beta-hemolytic streptococci 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.

For those patients with soft tissue infection who were initiated on parenteral therapy, a switch to an oral regimen is reasonable following clinical improvement [30,31].

Duration of antibiotics and follow-up — We typically follow patients with skin and soft tissue infection at least weekly until resolution of infection, and we expect to see steady improvement at each follow-up visit. Most mild soft tissue diabetic foot infections will resolve within one to two weeks of therapy. Some patients may require extended treatment (up to four weeks), particularly those with moderate to severe infection [5,15,31]. If the patient underwent resection of the entire area of infection, a brief course of oral antibiotic therapy (less than five days) following surgery is usually sufficient [30].

For patients whose infections show no improvement or fail to resolve, broadening coverage to include activity against MRSA, aerobic gram-negative bacilli, and/or anaerobes may be appropriate. However, in many cases, the cause for clinical failure is unrelated to antibiotic selection. A residual nidus of infection, such as abscess or necrotic tissue, may need to be debrided before the infection can resolve. Other common causes of clinical failure include lack of appropriate wound care, or peripheral artery disease or edema limiting tissue penetration of the antibiotic into the site of infection.

OSTEOMYELITIS — 

Surgical intervention, antibiotic therapy, and wound management are primary components of treating osteomyelitis.

Role of surgery — The primary role of surgery is to remove infected nonviable tissue (bone and soft tissue). Surgery also allows bone biopsy to be obtained for culture.

Indications for surgery — Many patients who have soft tissue infection overlying osteomyelitis require surgery based on the severity or extent of their soft tissue infection, as described above (see 'Indications for surgery' above). For these patients, surgical debridement of underlying osteomyelitis should be performed during debridement of the overlying soft tissue infection.

For patients with osteomyelitis of the foot who don’t have a clear indication for soft tissue debridement, the decision to operate is more nuanced. Surgical resection is traditionally thought to be the standard of care for osteomyelitis. However, patients with diabetes are at particular risk for poor wound healing following surgery due to peripheral artery disease, peripheral neuropathy, and other comorbidities. (See "Susceptibility to infections in persons with diabetes mellitus", section on 'Host factors'.).

Some observational data and one small randomized trial suggest that outcomes are similar regardless of whether surgery is performed [32-37]. A 2022 meta-analysis found success rates of 68 percent for patients treated with antibiotic therapy compared with 86 percent for surgery combined with antibiotics, with the caveat that the included studies were heterogeneous in how they defined osteomyelitis and treatment failure [33]. One small randomized trial comparing 90 days of antibiotic therapy to debridement (without amputation) plus 10 days of antibiotic therapy found no difference in rates of subsequent need for surgery or amputation [34].

Guidelines suggest (with low certainty evidence) that foregoing surgery may be considered in patients who meet all of the following criteria [5]:

●Infection confined to forefoot (metatarsals and/or phalanges),

●No indication for surgical debridement of soft tissue infection (see 'Indications for surgery' above),

●No significant peripheral artery disease, and

●No exposed bone.

If surgery is performed, formal vascular evaluation is important because revascularization (via angioplasty or bypass grafting) may be necessary to optimize wound healing or may limit the ultimate extent of surgical intervention [1,5,13]. (See 'Indications for surgery' above and "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'.)

Extent of surgery — Surgery for osteomyelitis involves either debridement (removal of infected and necrotic tissue), resection (removal of a piece of bone), or amputation (removal of part or all of a bone or bones).

Extensive resections and amputations may adversely alter the biomechanics of the foot, increasing the risk of future ulceration or immobility. For this reason, debridement is often favored over resection, and partial amputation (eg, ray or transmetatarsal amputation) is favored over below- or above-knee amputations. The main drawback of debridement or partial resections is the possibility of infected bone remaining after surgery. Outcomes-data comparing debridement with resection or amputation are scarce [5,38-42].

Bone biopsy — If surgery is performed for osteomyelitis, bone samples should be obtained during surgery to confirm the diagnosis of osteomyelitis and guide antibiotic selection. The value and technique for bone samples is discussed in detail separately. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Bone biopsy' and "Osteomyelitis in the absence of hardware: Approach to diagnosis in adults", section on 'Bone biopsy as gold standard'.)

Antibiotic selection — Limited data on antibiotic therapy of diabetic foot osteomyelitis do not allow comparison of outcomes of different regimens [23].

Timing of antibiotics — Patients with osteomyelitis who have significant soft tissue infection or severe illness should receive antibiotic therapy without delay to prevent the infection from spreading along soft tissue planes or into the bloodstream.

For patients who have little to no evidence of overlying soft tissue infection, delaying antibiotic therapy until after a bone sample is obtained is reasonable to potentially optimize the microbiologic yield of bone culture. For example, patients with a chronic foot ulcer that fails to improve despite optimal wound therapy should be evaluated for underlying osteomyelitis; in such cases, withholding antibiotic therapy and obtaining a bone biopsy can help to confirm the presence of osteomyelitis and guide subsequent antibiotic therapy. (See "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Diagnosis of underlying osteomyelitis'.)

Oral versus intravenous route — In the United States, osteomyelitis has traditionally been treated with intravenous antibiotics. However, increasing numbers of studies suggest that oral antibiotic therapy is as effective as intravenous in many situations, including for diabetic foot osteomyelitis. (See "Osteomyelitis in the absence of hardware: Approach to treatment in adults", section on 'Evidence comparing oral to intravenous therapy'.)

Intravenous therapy — Intravenous therapy should be administered as initial therapy to patients with severe or limb-threatening soft tissue infection and other clinical findings that suggest the need for immediate hospitalization.

Once soft tissue infection has been stabilized and purulent and necrotic bone tissue has been debrided, the decision to transition to oral therapy or continue intravenous therapy for the full duration of treatment should be based on clinical features, microbiology, and patient-preference.

Prolonged outpatient intravenous therapy may be necessary in certain situations (table 4):

●Extensive remaining infected tissue with inability to undergo debridement.

●Suspected or proven infection with a pathogen for which no highly bioavailable oral antibiotic options exist.

●Inability to use oral options due to side effects, drug allergies, contraindications, or drug-drug interactions.

●Inability to absorb or tolerate oral options.

●Significant lower extremity ischemia (including microvascular disease) or edema that may hinder antibiotic delivery to the site of infection. This criterion may be especially important if the only oral options have poor bioavailability (ie, the agent cannot achieve high blood concentrations via the oral route).

Empiric intravenous therapy for moderate diabetic foot osteomyelitis includes activity against streptococci, S. aureus (and methicillin-resistant S. aureus [MRSA] if risk factors are present), aerobic gram-negative bacilli (including Pseudomonas spp if at risk), and anaerobes. For severe infection, MRSA and Pseudomonas coverage is always included. (See 'Classifying the severity of illness' above and 'Indications for MRSA coverage' above and 'Indications for coverage of Pseudmonas' above.)

Specific intravenous regimens are outlined in the table (table 4), and example regimens are listed below:

●Without an indication for Pseudomonas coverage – Intravenous ceftriaxone (2 g intravenously once daily) plus metronidazole (500 mg orally or intravenously every 8 to 12 hours) or intravenous piperacillin-tazobactam (3.375 g intravenously every six hours).

If MRSA coverage is indicated, add intravenous vancomycin (table 5) or daptomycin (table 4).

●With an indication for Pseudomonas coverage – Intravenous cefepime (2 g intravenously every eight hours) plus metronidazole (500 mg orally or intravenously every 8 to 12 hours) or piperacillin-tazobactam (4.5 g intravenously every six hours).

If MRSA coverage is indicated, add intravenous vancomycin (table 5) or daptomycin (table 4).

Once bone culture and susceptibilities are available, the regimen should be tailored to target isolated pathogens. There is not sufficient data to make definitive recommendations regarding when anaerobic coverage is needed and for how long (see "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Anaerobic organisms'). Example regimens are listed in the table (table 6).

Oral therapy — Oral therapy for osteomyelitis of the foot in patients with diabetes has been an acceptable practice for longer than for other forms of osteomyelitis. Oral administration offers convenience, eliminates risk of catheter-related complications, and may lower costs. However, in certain situations, intravenous therapy is more appropriate, as discussed above. (See 'Intravenous therapy' above.)

We consider oral antibiotics for patients in who meet certain criteria (algorithm 1):

●Infection is not severe or limb-threatening.

●Minimal remaining necrotic tissue, abscess, or other nidus of infection.

●A highly bioavailable oral option is available to treat the suspected or proven pathogen(s).

●Able to absorb oral medications. Clinicians should check for concomitant medication that may hinder absorption. For example, calcium supplements, multivitamins, antacids, and sucralfate can decrease fluoroquinolone absorption.

●There are no concerning side effects, allergies, contraindications, or drug-drug interactions.

●Compliance with oral therapy can be assured or carefully monitored.

●Minimal or no lower extremity ischemia (including microvascular disease) or edema significant enough to hinder antibiotic delivery to the site of infection. This criterion may be especially important if the only oral options have poor bioavailability (ie, the agent cannot achieve high blood concentrations via the oral route).

Oral therapy may also be preferred if intravenous therapy is unfeasible based on nonclinical reasons (eg, inability to manage home outpatient therapy, cost).

For empiric oral therapy in stable outpatients who don’t require hospitalization, we prefer the following regimens (algorithm 1):

●Amoxicillin-clavulanate [7,30,34,43]

●Levofloxacin, with or without metronidazole [34,43,44]

●Moxifloxacin

●Trimethoprim-sulfamethoxazole (TMP-SMX) with or without metronidazole

●Ciprofloxacin plus clindamycin (alternate)

In cases where the patient has received one or more short courses of antibiotics prior to osteomyelitis treatment and there are no deep cultures available, some would consider double coverage of gram-negative organisms with regimens such as doxycycline or TMP-SMX plus amoxicillin-clavulanate.

If bone cultures reveal a specific organism, the regimen should be tailored accordingly. In general, we avoid beta-lactam antibiotics other than amoxicillin-clavulanate because clinical studies are lacking and bioavailability may be more limited. We generally continue anaerobic coverage even if cultures do not grow an anaerobic organism. However, there is not sufficient data to make definitive recommendations regarding this issue or the most appropriate duration of anaerobic coverage. (See "Osteomyelitis in the absence of hardware: Approach to treatment in adults", section on 'Oral regimens used in studies' and "Diabetic foot infection, including osteomyelitis: Clinical manifestations and diagnosis", section on 'Anaerobic organisms'.)

Randomized trials directly comparing oral therapy with intravenous specifically for diabetic foot osteomyelitis are scarce, although trials comparing oral regimens with each other suggest efficacy [7,30,34,43,44]. Additionally, a randomized trial of 1054 patients with osteomyelitis of any type found no difference in failure rate with oral therapy (13 percent) versus intravenous (15 percent); the proportion of infections that were diabetic foot osteomyelitis is unclear [45].

Observational studies of patients with diabetic foot osteomyelitis lend further support for oral therapy [27,46-49].

Further discussion of oral versus intravenous therapy for osteomyelitis is found separately. (See "Osteomyelitis in the absence of hardware: Approach to treatment in adults", section on 'Evidence comparing oral to intravenous therapy'.)

Duration of therapy — The duration of antibiotic therapy of osteomyelitis depends on the extent of residual affected tissue and the clinical response. The route of administration (ie, oral versus intravenous) does not necessarily affect duration.

Ultimately, clinical judgement is necessary to determine when to stop antibiotics.

●Residual infected bone – We typically treat these patients for six weeks from the date of the last debridement. If local debridement was performed without complete resection or amputation, we treat as if residual infected bone is present.

If we are uncertain whether residual infected bone remains after surgical intervention, we use a combination of the following factors to determine duration of therapy: intraoperative findings as described by the surgeon, preoperative radiographic findings compared to level of surgery, "bone margin" pathology obtained intraoperatively, and "bone margin" cultures obtained intraoperatively. The clinical significance of a positive or negative bone margin alone following surgery is uncertain [50-54] and we review these results in the context of other findings such as whether the surgeon believes there is residual infection.

Data suggest that treatment beyond six weeks is usually unnecessary, even in the presence of residual infection [29,44]. Occasionally, we will treat with longer durations of therapy if an infection is slowly improving but hasn’t completely resolved. Emerging data suggest that durations shorter than six weeks may be sufficient [43], but we continue to follow a conservative approach until more data become available.

●No residual infected bone – These are patients who underwent amputation or complete resection of infected bone. (See 'Extent of surgery' above.)

In the absence of residual soft tissue infection, we agree with expert guidelines that antibiotics may not be necessary at all, and no more than five days of antibiotics should be administered.

If soft tissue infection is present, the duration should be dependent on resolution of the soft tissue infection, as described above. (See 'Duration of antibiotics and follow-up' above.)

Duration of treatment for osteomyelitis in general is discussed in detail elsewhere. (See "Osteomyelitis in the absence of hardware: Approach to treatment in adults", section on 'Duration of therapy'.)

Follow-up — Patients with diabetic foot osteomyelitis require prolonged follow-up because relapse or recurrence can occur months after apparent resolution of infection. Most providers would not consider a patient’s osteomyelitis “cured” until 6 to 12 months after completion of therapy [5].

Patients who worsen while on therapy should be evaluated for possible causes, especially residual nidus of infection (eg, necrotic bone, abscess) that requires further debridement. Other common causes of clinical failure include lack of appropriate wound care, peripheral artery disease, edema, resistant pathogens, and noncompliance with offloading bone sampling may help to guide further antibiotic treatment if other causes of failure cannot be identified.

Follow-up inflammatory markers (eg, erythrocyte sedimentation rate [ESR], C-reactive protein [CRP]) are not necessarily helpful for determining response to or duration of therapy. Although studies suggest that inflammatory markers improve on therapy, whether they provide actionable information beyond clinical observation is unclear [55]. Follow-up imaging is not recommended unless there is concern for progression of disease or soft tissue infection.

WOUND MANAGEMENT — 

Local wound and skin care for diabetic foot infections is of paramount importance to promote healing and prevent future infections. Important components include off-loading (relieving pressure on the wound), intermittent debridement if necessary, dressings, and other interventions as described in detail separately. (See "Management of diabetic foot ulcers".)

ADJUNCTIVE THERAPIES — 

Adjunctive therapies for treatment of diabetic foot infections include vacuum-assisted wound closure, hyperbaric oxygen, topical agents (antibiotics, antiseptics, honey, silver preparations, bacteriophage therapy, oxygen, bioactive glass), and granulocyte colony-stimulating factor (G-CSF) [5] .

Of these, vacuum-assisted wound closure is used most frequently, and is discussed elsewhere. We agree with expert guidelines that the other listed adjunctive therapies be avoided [5].

PREVENTION — 

The mainstays of preventing diabetic foot infections focus on preventing foot wounds:

●Regular foot examinations by the patient and clinicians

●Proper shoe fittings and off-loading

●Attentive wound management if an ulcer develops

●Vascular evaluation and intervention for significant peripheral artery disease

●Optimal glycemic control

There is no role for antibiotics for uninfected or colonized ulcers, as discussed above. (See 'No role for treatment of colonized ulcers' above.)

OUTCOMES — 

Outcomes data vary in studies, partially due to the wide variation of illness in patients with diabetic foot infections. Amputations are not uncommon. In an observations study of 299 patients with infected diabetic foot ulcers the United Kingdom, amputation was required in 52 (17 percent), and 45 (15 percent) died within one year of treatment [56].

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".)

SUMMARY AND RECOMMENDATIONS

●General approach – Management of diabetic foot infection requires a multifaceted approach involving clinicians from different specialties. (See 'General approach' above.)

●Determining site of care – Severity of illness determines the need for hospitalization. Many patients with mild or moderate infections can be managed as outpatients with close follow-up. (See 'Determining site of care' above.)

●Skin and soft tissue infection – Components of management of skin and soft tissue diabetic foot infections are surgical consultation, antibiotic therapy, and wound management. (See 'Skin and soft tissue infection without osteomyelitis' above.)

•Role of surgery – Early surgical consultation can prevent amputation. (See 'Role of surgery' above.)

-Indications for surgery – Urgent surgical debridement is necessary for deep abscess, extensive bone or joint involvement, crepitus, necrosis, gangrene, necrotizing fasciitis, and compartment syndrome. Severe lower extremity ischemia should be corrected via angioplasty or bypass. (See 'Indications for surgery' above.)

-Obtaining soft tissue cultures – Deep tissue cultures obtained during surgery can guide antibiotic selection. Other methods of obtaining deep culture include bedside curettage or percutaneous abscess sampling. Superficial swabs of wounds are not predictive of causative pathogens. (See 'Obtaining soft tissue cultures' above.)

•Empiric antibiotic selection for soft tissue infection – Severity of illness and suspected pathogens dictate antibiotic selection. (See 'Classifying the severity of illness' above and 'Indications for MRSA coverage' above and 'Indications for coverage of Pseudmonas' above.).

-Mild infection – Mild infections are usually treated with outpatient oral antibiotics. We suggest regimens that include coverage against beta-hemolytic streptococci and Staphylococcus aureus (Grade 2C). For patients with risk factors for methicillin-resistant S. aureus (MRSA), we choose a regimen with MRSA coverage. For patients with previous antibiotic exposure within the prior four to six weeks, we choose a regimen with activity against Enterobacterales (algorithm 1). (See 'Mild infection' above.)

An example regimen for patients without recent antibiotic exposure is cephalexin (500 mg orally every six hours). If MRSA is suspected, an example regimen is trimethoprim-sulfamethoxazole (one to two double-strength tablets orally twice daily).

-Moderate infection – Oral therapy is appropriate for many moderate infections. We suggest an antibiotic regimen with activity against streptococci, S. aureus, aerobic gram-negative bacilli, and anaerobes; our preferred regimen is amoxicillin-clavulanate (875 mg orally every 12 hours) (Grade 2B). We add an additional antibiotic if MRSA (eg, trimethoprim-sulfamathoxazole [TMP-SMX]) or Pseudomonas (eg, ciprofloxacin 750 mg orally every 12 hours) risk factors are present (algorithm 1). (See 'Moderate infection' above.)

Intravenous options for moderate infection are outlined in the table (table 4).

-Severe infection – We suggest treating limb-threatening or severe diabetic foot infections with intravenous antibiotics with activity against streptococci, MRSA, aerobic gram-negative bacilli (including Pseudomonas spp), and anaerobes (table 4) (Grade 2C). An example regimen is vancomycin (table 5) plus piperacillin-tazobactam (4.5 g intravenously every six hours). (See 'Severe infection' above.)

●Osteomyelitis – Surgical intervention, antibiotic therapy, and wound management are primary components of treating osteomyelitis. (See 'Osteomyelitis' above.)

•Role of surgery – Surgery removes infected nonviable tissue (bone and soft tissue) and allows bone biopsy to be obtained for culture. For patients with a soft tissue infection that requires surgical debridement, the underlying osteomyelitis should also be debrided during surgery. The decision to operate in patients without a clear indication for soft tissue debridement is more nuanced. (See 'Role of surgery' above.)

•Empiric antibiotic selection for osteomyelitis – Intravenous therapy should be administered as initial therapy to patients with severe or limb-threatening soft tissue infection.

Once soft tissue infection has been stabilized and purulent and necrotic bone tissue has been debrided, the decision to transition to oral therapy or continue intravenous therapy for the full duration of treatment is based on clinical features, microbiology, and patient-preference (table 4). (See 'Oral versus intravenous route' above.)

Empiric regimens should include activity against streptococci, S. aureus (MRSA if risk factors are present), aerobic gram-negative bacilli (including Pseudomonas spp if at risk), and anaerobes.

Example empiric regimens include:

-Intravenous regimen – Ceftriaxone (2 g intravenously once daily) plus metronidazole (500 mg orally or intravenously every 8 to 12 hours). If Pseudomonas spp is suspected, ceftriaxone can be replaced with cefepime (2 g intravenously every eight hours). If MRSA is suspected, vancomycin can be added (table 4). (See 'Intravenous therapy' above.)

-Oral regimen – Amoxicillin-clavulanate (875 mg orally every 12 hours) is our preferred regimen (Grade 2B). Regimens for patients in whom MRSA or Pseudomonas is suspected are outlined in the algorithm (algorithm 1). (See 'Oral therapy' above.)

●Duration of antibiotic therapy – Skin and soft tissue infections without osteomyelitis typically require one to two weeks of antibiotic therapy. (See 'Duration of antibiotics and follow-up' above.)

For patients with osteomyelitis who do not undergo amputation, we typically treat for six weeks from the data of the last debridement. (See 'Duration of therapy' above.)

Antibiotics should be adjusted based on culture and susceptibility results.

●Wound management – Local wound and skin care for diabetic foot infections are of paramount importance to promote healing and prevent future infections. (See 'Wound management' above.)