Warren S. Joseph

Diagnosis and Treatment of Diabetic Foot Infections

EXECUTIVE SUMMARY: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limbs arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III).

2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections a

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

Diagnosis and treatment of diabetic foot infections

Executive Summary: 1. Foot infections in patients with diabetes cause substantial morbidity and frequent visits to health care professionals and may lead to amputation of a lower extremity. 2. Diabetic foot infections require attention to local (foot) and systemic (metabolic) issues and coordinated management, preferably by a multidisciplinary foot-care team (A-II) (Table 1). The team managing these infections should include, or have ready access to, an infectious diseases specialist or a medical microbiologist (B-II). 3. The major predisposing factor to these infections is foot ulceration, which is usually related to peripheral neuropathy. Peripheral vascular disease and various immunological disturbances play a secondary role. 4. Aerobic Gram-positive cocci (especially Staphylococcus aureus) are the predominant pathogens in diabetic foot infections. Patients who have chronic wounds or who have recently received antibiotic therapy may also be infected with Gram-negative rods, and those with foot ischemia or gangrene may have obligate anaerobic pathogens. 5. Wound infections must be diagnosed clinically on the basis of local (and occasionally systemic) signs and symptoms of inflammation. Laboratory (including microbiological) investigations are of limited use for diagnosing infection, except in cases of osteomyelitis (B-II). 6. Send appropriately obtained specimens for culture before starting empirical antibiotic therapy in all cases of infection, except perhaps those that are mild and previously untreated (B-III). Tissue specimens obtained by biopsy, ulcer curettage, or aspiration are preferable to wound swab specimens (A-I). 7. Imaging studies may help diagnose or better define deep, soft-tissue purulent collections and are usually needed to detect pathological findings in bone. Plain radiography may be adequate in many cases, but MRI (in preference to isotope scanning) is more sensitive and specific, especially for detection of soft-tissue lesions (A-I). 8. Infections should be categorized by their severity on the basis of readily assessable clinical and laboratory features (B-II). Most important among these are the specific tissues involved, the adequacy of arterial perfusion, and the presence of systemic toxicity or metabolic instability. Categorization helps determine the degree of risk to the patient and the limb and, thus, the urgency and venue of management. 9. Available evidence does not support treating clinically uninfected ulcers with antibiotic therapy (D-III). Antibiotic therapy is necessary for virtually all infected wounds, but it is often insufficient without appropriate wound care. 10. Select an empirical antibiotic regimen on the basis of the severity of the infection and the likely etiologic agent(s) (B-II). Therapy aimed solely at aerobic Gram-positive cocci may be sufficient for mild-to-moderate infections in patients who have not recently received antibiotic therapy (A-II). Broad-spectrum empirical therapy is not routinely required but is indicated for severe infections, pending culture results and antibiotic susceptibility data (B-III). Take into consideration any recent antibiotic therapy and local antibiotic susceptibility data, especially the prevalence of methicillin-resistant S. aureus (MRSA) or other resistant organisms. Definitive therapy should be based on both the culture results and susceptibility data and the clinical response to the empirical regimen (C-III). 11. There is only limited evidence with which to make informed choices among the various topical, oral, and parenteral antibiotic agents. Virtually all severe and some moderate infections require parenteral therapy, at least initially (C-III). Highly bioavailable oral antibiotics can be used in most mild and in many moderate infections, including some cases of osteomyelitis (A-II). Topical therapy may be used for some mild superficial infections (B-I). 12. Continue antibiotic therapy until there is evidence that the infection has resolved but not necessarily until a wound has healed. Suggestions for the duration of antibiotic therapy are as follows: for mild infections, 12 weeks usually suffices, but some require an additional 12 weeks; for moderate and severe infections, usually 24 weeks is sufficient, depending on the structures involved, the adequacy of debridement, the type of soft-tissue wound cover, and wound vascularity (A-II); and for osteomyelitis, generally at least 46 weeks is required, but a shorter duration is sufficient if the entire infected bone is removed, and probably a longer duration is needed if infected bone remains (B-II). 13. If an infection in a clinically stable patient fails to respond to 1 antibiotic courses, consider discontinuing all antimicrobials and, after a few days, obtaining optimal culture specimens (C-III). 14. Seek surgical consultation and, when needed, intervention for infections accompanied by a deep abscess, extensive bone or joint involvement, crepitus, substantial necrosis or gangrene, or necrotizing fasciitis (A-II). Evaluating the limb’s arterial supply and revascularizing when indicated are particularly important. Surgeons with experience and interest in the field should be recruited by the foot-care team, if possible. 15. Providing optimal wound care, in addition to appropriate antibiotic treatment of the infection, is crucial for healing (A-I). This includes proper wound cleansing, debridement of any callus and necrotic tissue, and, especially, off-loading of pressure. There is insufficient evidence to recommend use of a specific wound dressing or any type of wound healing agents or products for infected foot wounds. 16. Patients with infected wounds require early and careful follow-up observation to ensure that the selected medical and surgical treatment regimens have been appropriate and effective (B-III). 17. Studies have not adequately defined the role of most adjunctive therapies for diabetic foot infections, but systematic reviews suggest that granulocyte colony-stimulating factors and systemic hyperbaric oxygen therapy may help prevent amputations (B-I). These treatments may be useful for severe infections or for those that have not adequately responded to therapy, despite correcting for all amenable local and systemic adverse factors. 18. Spread of infection to bone (osteitis or osteomyelitis) may be difficult to distinguish from noninfectious osteoarthropathy. Clinical examination and imaging tests may suffice, but bone biopsy is valuable for establishing the diagnosis of osteomyelitis, for defining the pathogenic organism(s), and for determining the antibiotic susceptibilities of such organisms (B-II). 19. Although this field has matured, further research is much needed. The committee especially recommends that adequately powered prospective studies be undertaken to elucidate and validate systems for classifying infection, diagnosing osteomyelitis, defining optimal antibiotic regimens in various situations, and clarifying the role of surgery in treating osteomyelitis (A-III). Table 1. Infectious Diseases Society of America–United States Public Health Service Grading System for Ranking Recommendations in Clinical Guidelines

Executive Summary: 2012 Infectious Diseases Society of America Clinical Practice Guideline for the Diagnosis and Treatment of Diabetic Foot Infections

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

Ciclopirox 8% Nail Lacquer in the Treatment of Onychomycosis of the Toenails in the United States

Ciclopirox 8% nail lacquer has recently become the first topical antifungal agent to be approved by the US Food and Drug Administration for the treatment of onychomycosis. This article reviews the results of the two pivotal clinical trials of this drug that have been performed in the United States as well as those that have been carried out in other countries. The two US studies were both double-blind, vehicle-controlled, parallel-group, multicenter studies designed to determine the efficacy and safety of ciclopirox nail lacquer in the treatment of mild-to-moderate onychomycosis of the toenails caused by dermatophytes. The combined results show a 34% mycologic cure rate, as compared with 10% for the placebo. Data from the ten studies conducted worldwide show a meta-analytic mean (+/- SE) mycologic cure rate of 52.6% +/- 4.2%. As expected for a topical agent, ciclopirox nail lacquer was found to be extremely safe, with mild, transient irritation at the site of application reported as the most common adverse event. Ciclopirox nail lacquer may also have potential for use in combination or adjunctive therapy. Further studies will help to better position this agent for the treatment of this widespread podiatric condition.

2012 infectious diseases society of america clinical practice guideline for the diagnosis and treatment of diabetic foot infections.

Foot infections are a common and serious problem in persons with diabetes. Diabetic foot infections (DFIs) typically begin in a wound, most often a neuropathic ulceration. While all wounds are colonized with microorganisms, the presence of infection is defined by ≥2 classic findings of inflammation or purulence. Infections are then classified into mild (superficial and limited in size and depth), moderate (deeper or more extensive), or severe (accompanied by systemic signs or metabolic perturbations). This classification system, along with a vascular assessment, helps determine which patients should be hospitalized, which may require special imaging procedures or surgical interventions, and which will require amputation. Most DFIs are polymicrobial, with aerobic gram-positive cocci (GPC), and especially staphylococci, the most common causative organisms. Aerobic gram-negative bacilli are frequently copathogens in infections that are chronic or follow antibiotic treatment, and obligate anaerobes may be copathogens in ischemic or necrotic wounds. Wounds without evidence of soft tissue or bone infection do not require antibiotic therapy. For infected wounds, obtain a post-debridement specimen (preferably of tissue) for aerobic and anaerobic culture. Empiric antibiotic therapy can be narrowly targeted at GPC in many acutely infected patients, but those at risk for infection with antibiotic-resistant organisms or with chronic, previously treated, or severe infections usually require broader spectrum regimens. Imaging is helpful in most DFIs; plain radiographs may be sufficient, but magnetic resonance imaging is far more sensitive and specific. Osteomyelitis occurs in many diabetic patients with a foot wound and can be difficult to diagnose (optimally defined by bone culture and histology) and treat (often requiring surgical debridement or resection, and/or prolonged antibiotic therapy). Most DFIs require some surgical intervention, ranging from minor (debridement) to major (resection, amputation). Wounds must also be properly dressed and off-loaded of pressure, and patients need regular follow-up. An ischemic foot may require revascularization, and some nonresponding patients may benefit from selected adjunctive measures. Employing multidisciplinary foot teams improves outcomes. Clinicians and healthcare organizations should attempt to monitor, and thereby improve, their outcomes and processes in caring for DFIs.

The role of diabetes mellitus in the treatment of skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: results from three randomized controlled trials

OBJECTIVE To compare outcomes of treating complicated skin and skin structure infections (cSSSI) caused by methicillin-resistant Staphylococcus aureus (MRSA) with linezolid versus vancomycin in diabetic and non-diabetic patients. METHODS We pooled data from three prospective clinical trials in which 1056 patients were randomized to receive either linezolid (intravenous (IV) or oral) or vancomycin (IV) every 12h, for 7-28 days. RESULTS Diabetic (n=349) and non-diabetic patients (n=707) had comparable demographics and co-morbidities. Clinical success rates were lower in diabetic than in non-diabetic patients (72.3% and 85.8%, respectively). Overall, non-diabetic patients had a shorter adjusted mean length of stay (LOS) compared with diabetic patients (8.2 and 10.7 days, respectively; p<0.0001). Among diabetic patients, rates were comparable with linezolid and vancomycin treatment for clinical success (74% and 71%, respectively) and microbiological success (60% and 54%, respectively). Among non-diabetic patients, clinical and microbiological success rates were higher in linezolid- than in vancomycin-treated patients (90% and 81%, respectively, and 78% and 65%, respectively). Rates of drug-related adverse events were comparable in diabetic and non-diabetic patients and with linezolid and vancomycin treatment. Adjusted mean LOS was shorter with linezolid than with vancomycin treatment in diabetic patients (9.5 and 11.7 days, respectively; p=0.03) and non-diabetic patients (7.6 and 8.9 days, respectively; p=0.02). CONCLUSIONS Clinical success rates were lower in diabetic than non-diabetic patients with cSSSI caused by MRSA. Comparing linezolid and vancomycin, clinical and microbiological success rates were comparable in diabetic patients, but were better for linezolid than for vancomycin in non-diabetic patients.

Medical therapy of diabetic foot infections

Diabetic foot infections are a common and often serious problem, accounting for a greater number of hospital bed days than any other complication of diabetes. Despite advances in both antibiotic therapy and surgical management, these infections continue to be a major risk factor for amputations of the lower extremity. Although a number of wound size and depth classification systems have been adapted for use in codifying diabetic foot ulcerations, none are specific for infection. In 2003, the International Working Group on the Diabetic Foot developed guidelines for managing diabetic foot infections, including the first severity scale specific for these infections. The following year, the Infectious Diseases Society of America (IDSA) published their Diabetic Foot Infection Guidelines. In this article, we review some of the critical points from the Executive Summary of the IDSA document and provide a commentary following each issue to update the reader on any pertinent changes that have occurred since the publication of the original document in 2004. The importance of a multidisciplinary limb salvage team, apropos this special joint issue of the American Podiatric Medical Association and the Society for Vascular Surgery, cannot be overstated.

Medical therapy of diabetic foot infections.

Diabetic foot infections are a common and often serious problem, accounting for more hospital bed days than any other complication of diabetes. Despite advances in antibiotic drug therapy and surgical management, these infections continue to be a major risk factor for amputations of the lower extremity. Although a variety of wound size and depth classification systems have been adapted for use in codifying diabetic foot ulcerations, none are specific to infection. In 2003, the International Working Group on the Diabetic Foot developed guidelines for managing diabetic foot infections, including the first severity scale specific to these infections. The following year, the Infectious Diseases Society of America published their diabetic foot infection guidelines. Herein, we review some of the critical points from the Executive Summary of the Infectious Diseases Society of America document and provide a commentary following each issue to update the reader on any pertinent changes that have occurred since publication of the original document in 2004. The importance of a multidisciplinary limb salvage team, apropos of this special issue jointly published by the American Podiatric Medical Association and the Society for Vascular Surgery, cannot be overstated.

Patient satisfaction with oral versus nonoral therapeutic approaches in onychomycosis.

The follow-up results of a 9-month observational study of 150 onychomycosis patients treated with a variety of mechanical, topical, and oral therapies by podiatric physicians and dermatologists are presented. Changes from baseline in toenail condition and patient satisfaction were assessed at 4- and 9-month follow-up. At 9 months, patients who had received oral therapy reported significantly fewer onychomycosis-related problems in social situations, including embarrassment or self-consciousness about the appearance of nails, avoidance of contact by others, being perceived as unclean or untidy, and the desire to keep their nails concealed. Patient-reported satisfaction with the treatment program was significantly higher for those receiving oral therapy than for those receiving nonoral therapy.