Diabetic Foot Infections - Management

MANAGEMENT

Antibiotic Therapy

                Diabetic foot infection may be limb- or even life-threatening and may progress rapidly. Too narrow an empiric antibiotic regimen may therefore lead to a poor clinical outcome. Furthermore, diabetic foot infections are commonly polymicrobial. Thus, clinicians should generally opt for broad-spectrum empiric therapy while awaiting culture and sensitivity results. This is not, however, always necessary. Unnecessarily broad-spectrum therapy also has potential adverse consequences, such as increasing antibiotic resistance (a potential problem for both the individual patient and society as a whole), increased financial cost, and potentially increased risk of drug toxicity. Properly obtained specimens for microbial evaluation are crucial to optimally direct antibiotic therapy and to potentially allow the empiric antibiotic regimen to be narrowed or targeted.

                Deciding upon an empiric antibiotic regimen for diabetic foot infection is challenging, but understanding some basic principles can guide clinicians. An important place to start is to realize that about half of diabetic foot wounds have no clinical evidence of infection. Some believe that the presence of a high density of organisms, usually defined as >105 per gram of tissue, represents “critical colonization” that may require antibiotic therapy, but the few published trials of antibiotic therapy for uninfected lesions do not support this practice. Thus, clinically uninfected wounds generally require neither a culture nor antibiotic therapy.

               For clinically infected lesions, mild, and most moderate, infections (Table 3) can be treated with relatively narrow spectrum agents predominantly directed at staphylococci and streptococci. An exception to this would be a patient who has recently been treated with an antibiotic. This may predispose to infection with more unusual and antibiotic resistant organisms. More severe infections generally mandate a broader-spectrum regimen. All empiric regimens should cover aerobic gram-positive cocci, especially Staphylococcus aureus, since they are the most frequently isolated organism from a diabetic foot infection (acute and chronic; mild, moderate and severe).

Table 3. Clinical Classification of Diabetic Foot Infections

Infection* severity	Clinical manifestations of infection
Uninfected	Wound lacking purulence or any manifestations of inflammation
Mild	Infection localized to the skin and subcutaneous  tissue (cellulitis/erythema extends ≤2 cm around an ulcer) without evidence of systemic illness
Moderate	More extensive local infection (i.e., local spread ≥2cm beyond an ulcer, lymphangitic streaking, abscess, gangrene, or involvement of deep soft tissue, muscle, fascia, tendon, joint or bone) without evidence systemic illness or severe metabolic derangements
Severe	Infection with systemic toxicity or severe metabolic derangements

* Infection defined as the presence of purulent secretions (pus) or ≥2 signs or symptoms of inflammation

(erythema, warmth, tenderness, induration, pain)

                The decision as to whether or not to provide empiric coverage for MRSA is based on the presence of known risk factors. For healthcare associated MRSA, this would include recent hospitalization or institutionalization, recent antibiotic therapy, frequent contact with or residence in a healthcare facility, and requirement for renal dialysis. Factors increasing the likelihood for community-acquired MRSA include a high local prevalence rate, suggestive clinical features of the infection such as cellulitis with central necrosis (often mistaken for a “spider bite” by patients), or involvement in team sports associated with skin abrasions or physical contact.

               Aerobic gram-negative bacilli are also commonly isolated as part of a polymicrobial infection (I), especially in a chronic wound in a patient who has received antibiotic therapy. Because Pseudomonas aeruginosa is a hydrophilic organism, hydrotherapy (e.g., soaking the affected foot in water or debridement with water lavage) is the main risk factor. Even when isolated in diabetic foot infection, Pseudomonas is usually part of a mixed infection and rarely the predominant pathogen. Selecting a regimen aimed at this frequently antibiotic resistant organism should thus be reserved for patients with one of the noted risk factors or who have green-blue colored wound drainage (Table 2) and a more severe infection(II). Notably, recent reports from developing countries with a tropical or arid climate have shown more frequent isolation of aerobic gram-negative bacilli than gram-positive cocci. The cause of this finding uncertain, but it may be a consequence of excessive sweating into shoes or wearing open or no footwear with exposure to the soil. Clinicians in such regions may consider broader spectrum (i.e., covering both aerobic gram-negative bacilli and gram-positive cocci) empirical therapy.

I. Polymicrobial diabetic foot infection	II. Debridement of an infected foot ulcer

 

Table 2. Pathogens Associated with Diabetic Foot Infection Syndromes

MRSA = Methicillin-resistant Staphylococcus aureus

ESBL = Extended spectrum beta-lactamase

                Obligate anaerobic bacteria are isolated from a substantial minority of cases, but almost always as part of a polymicrobial infection and usually associated with a chronic wound. Anaerobes are more often isolated from necrotic or gangrenous wounds with limb ischemia. A foul, feculent odor (the so called “fetid foot”) is also a clue to infection with anaerobes. Since oxygen is a potent anti-anaerobic agent, adequate treatment may require only debridement of necrotic tissue and exposing the remaining organisms to air. An empiric antibiotic regimen directed at anaerobic organisms may be appropriate when clinical suspicion is high and the infection is moderate to severe. The anaerobes in diabetic foot infection are mainly gram-positives (peptococci or peptostreptococci) rather than Bacteroides spp. Especially with anaerobic infections, antibiotic therapy is no substitute for adequate debridement and drainage.

               One final consideration is fungal infection. While tinea infections of the web spaces between the toes and onychomycosis are frequent in diabetic patients, pathogenic fungal infections are not. Occasionally, however, a patient who has received multiple antibiotics, who has severe hyperglycemia, or who is receiving corticosteroid therapy will develop an invasive soft tissue fungal infection.

                Surprisingly few studies have been performed to assess the efficacy of various antibiotics to treat diabetic foot infection. Furthermore, the available studies are not well standardized, making comparisons difficult. In virtually all comparative studies the regimens produced equivalent results. Thus, while several agents have been used successfully to treat diabetic foot infection, no specific antibiotic regimens have emerged as being preferred for a particular type of infection. Based on a review of available studies, the IDSA formulated suggested antibiotic regimens for the treatment of soft-tissue diabetic foot infection, as shown in Table 6. The general approach is to select as narrow spectrum, safe, and convenient a regimen as possible (Figure 4, IDSA guidelines). In about two-thirds of patients this will need to be empiric. When culture (or Gram-stained smear) results are available, the clinician should of course use this information. After 2-3 days, the clinician should reassess the patient and the infection and consider altering the definitive regimen based on the culture and sensitivity results and the patient’s clinical response to the selected regimen.

Table 6. Suggested Antibiotic Regimens for the Treatment of Soft-Tissue Diabetic Foot Infections

*Based on published evidence of efficacy for complicated skin infection or diabetic foot infections. Choice should be based on any available culture results, clinical factors (allergies, co-morbidities, etc.), local antibiotic susceptibility data, availability and cost.

               Mild infections may be treated with relatively narrow spectrum oral therapy directed at these aerobic gram-positive cocci, such as penicillinase-resistant penicillins (e.g., dicloxacillin), first-generation cephalosporins (e.g., cephalexin), or clindamycin. Some mildly infected wounds can be treated with topical antimicrobial therapy, either antiseptics (e.g., silver or iodine based) or antibiotic (e.g., mupirocin or bacitracin) but there are currently few published studies to support this approach. New topical products are now undergoing testing and may emerge as useful treatments for selected cases.

                Moderate (III) to severe infections (IV) often necessitate empirical regimens with activity against commonly isolated gram-negative bacilli, MRSA (if there are risk factors as previously discussed) and perhaps Enterococcus species. Enterococci are relatively frequent isolates, especially in patients previously treated with cephalosporins, but they are often colonizers and rarely primary pathogens. Broadening empirical antibiotic coverage based on previously mentioned clinical findings (Table 1) is often appropriate. As a general rule, we err on the side of overly broad initial coverage, put our effort into obtaining high quality specimens for culture, ensuring proper wound care and thinking more about the definitive antibiotic regimen to complete the course when culture results are available. We think most errors in treatment consist of failing to alter (and curtail) antibiotic therapy rather than in making a poor initial antibiotic choice.

III.

Moderate soft tissue infection of hammer toes	Septic great toe after surgery		Diabetic foot infection with gangrene	Necrotic toe and dorsal abscess from tight shoes

IV.

Moderate-to-severe diabetic foot infection with gangrene of the great toe	Severe diabetic foot infection

Table 1. Risk Factors for Foot Ulceration and Infection

               Additional considerations include the site of treatment and route of drug administration. Intravenous antibiotic therapy and hospitalization are not only costly but also potentially expose patients to iatrogenic complications and nosocomial infection. The severity of infection is usually the most important determinant of the need for hospitalization. Other factors may also influence the decision, such as the clinician’s desire to closely monitor the wound and response to treatment, a need for expedited diagnostic testing or consultant evaluation, and adverse social circumstances (e.g., inability of the patient to adequately care for the wound, off-load the foot, or uncertainty regarding compliance with antibiotics or follow-up care). Most patients with mild to moderate infections can be successfully treated as outpatients with oral antibiotic therapy. Many oral antibiotics have high bioavailability allowing therapeutic serum levels. An antibiotic’s pharmacokinetic and pharmacodynamic properties determine its serum, and therefore tissue, levels. When parenteral therapy is needed, it can often be offered by outpatient intravenous therapy with a once daily agent when this service is available. The arterial supply to the foot must also be adequate to ensure delivery of therapeutic antibiotic levels to the infected tissue.

                After wound culture and antibiotic susceptibility results become available, the clinician should consider narrowing the antibiotic coverage to the isolated pathogen(s). Clinical assessment of the patient and wound, including the response to the empirical regimen, are paramount in tailoring the antibiotic regimen. If the wound is clinically responding, it is reasonable to continue an empirical regimen, even if it does not have activity against all the isolated organisms. Conversely, if a wound is not improving, broaden antibiotic coverage to cover all isolated organisms, even those whose pathogenicity is uncertain. The optimal duration of antibiotic therapy has not been studied, but we recommend one to two weeks for mild to moderate soft tissue infections and at least two weeks (occasionally longer) for deeper or more complex soft tissue infections (Table 7). It is not usually necessary to continue antibiotic therapy for soft tissue infections beyond the point when all clinical signs if infection have resolved .

Debridement of an infected foot ulcer	Probing of a diabetic foot ulcer after debridement

 

Table 7. Suggested Route, Setting, and Duration of Antibiotic Therapy by Clinical Syndrome

OPAT = Outpatient antibiotic therapy

* Treat until resolution of all (or most) of the original symptoms and signs of infection

** With or without concurrent soft tissue infection

Surgical Intervention

                Surgical procedures designed to control infection and preserve as much the affected limb as possible are frequently required in the treatment of diabetic foot infection. Early, thorough debridement of infected and necrotic tissue helps define the extent of infection and may reduce the likelihood of future amputation. Severe infections may be immediately limb-threatening and require urgent surgical consultation. Unexplained, persistent foot pain, particularly in a patient known to have advanced neuropathy (i.e., a previously insensate foot) or distortion of the superficial anatomy (e.g., bulging of the plantar surface (V) or dorsal induration (VI) in a patient with a plantar ulcer) may indicate deep space infection that warrants prompt evaluation by a surgeon. When amputation is necessary, the surgeon should make every effort to perform a minor (below the ankle) rather than a major amputation to preserve functionality. If severe peripheral arterial disease is present, a vascular surgeon should be consulted promptly. Non-urgent amputation should rarely be done without a vascular surgery consultation. Early revascularization (i.e., within days) is generally preferred to delaying the procedure for a prolonged course of potentially ineffective antibiotic therapy. Endovascular or bypass procedures can be limb salvaging in some patients with a diabetic foot infection.

V.  Soft tissue abscess of 1st MTP area	VI.  Bulging foot abscess on the dorsal surface

Wound Care         After the initial assessment and treatment, the patient requires ongoing wound care. Regular follow-up evaluations and repeated debridement of any residual dead tissue can help promote continued healing. Many dressings and wound-care products are marketed but none are favored based on evidence. A moist dressing that allows daily wound inspection is optimal. The roles of adjunctive treatments such as hyperbaric oxygen and granulocyte colony stimulating factors have not yet been adequately defined. Meta-analyses of these treatments suggest that an as yet undefined subset of patients may benefit from these treatments. Considering their cost they should rarely be used as initial therapy but rather reserved for patients who are not responding to what should otherwise be appropriate treatment.