Although many antimicrobial agents display good in vitro activity against the pathogens frequently implicated in diabetic foot infections, effective treatment can be complicated by reduced tissue penetration in this population secondary to peripheral arterial disease and emerging antimicrobial resistance, which can result in clinical failure. Improved characterization of antibiotic tissue pharmacokinetics and penetration ratios in diabetic foot infections is needed. Microdialysis offers advantages over the skin blister and tissue homogenate studies historically used to define antibiotic penetration in skin and soft-tissue infections by defining antibiotic penetration into the interstitial fluid over the entire concentration versus time profile. However, only a select number of agents currently recommended for treating diabetic foot infections have been evaluated using these methods, which are described herein. Better characterization of the tissue penetration of antibiotic agents is needed for the development of methods for maximizing the pharmacodynamic profile of these agents to ultimately improve treatment outcomes for patients with 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. (J Am Podiatr Med Assoc 100(5): 395–400, 2010)
Foot complications are common in diabetic patients; foot ulcers are among the more serious consequences. These ulcers frequently become infected, and if not treated promptly and appropriately, diabetic foot infections can lead to septic gangrene and amputation. Foot infections may be classified as mild, moderate, or severe; this largely determines the approach to therapy. Staphylococcus aureus is the most common pathogen in these infections, and the increasing incidence of methicillin-resistant S aureus during the past two decades has further complicated antibiotic treatment. Chronic infections are often polymicrobial. Physiologic changes, and local and systemic inflammation, can affect the plasma and tissue pharmacokinetics of antimicrobial agents in diabetic patients, leading to impaired target-site penetration. Knowledge of the serum and tissue concentrations of antibiotics in diabetic patients is, therefore, important for choosing the optimal drug and dose. This article reviews the commonly used therapeutic options for treatment, including many newer antibiotics developed to target multidrug-resistant gram-positive bacteria, and includes available data relating specifically to the tissue penetration of these agents. (J Am Podiatr Med Assoc 100(1): 52–63, 2010)
Diabetic foot disease frequently leads to substantial long-term complications, imposing a huge socioeconomic burden on available resources and health-care systems. Peripheral neuropathy, repetitive trauma, and peripheral vascular disease are common underlying pathways that lead to skin breakdown, often setting the stage for limb-threatening infection. Individuals with diabetes presenting with foot infection warrant optimal surgical management to affect limb salvage and prevent amputation; aggressive short-term and meticulous long-term care plans are required. In addition, the initial surgical intervention or series of interventions must be coupled with appropriate systemic metabolic management as part of an integrated, multidisciplinary team. Such teams typically include multiple medical, surgical, and nursing specialties across a variety of public and private health-care systems. This article presents a stepwise approach to the diagnosis and treatment of diabetic foot infections with emphasis on the appropriate use of surgical interventions and includes the following key elements: incision, wound investigation, debridement, wound irrigation and lavage, and definitive wound closure. (J Am Podiatr Med Assoc 100(5): 401–405, 2010)
Diabetic foot infection (DFI) is a serious, difficult-to-treat infection, especially when caused by methicillin-resistant Staphylococcus aureus (MRSA). Vancomycin has been the standard treatment for MRSA infection, but lower response rates in MRSA skin infections have been reported. This analysis assessed the outcome and safety of daptomycin therapy in patients with a DFI caused by MRSA.
Using the Cubicin Outcomes Registry and Experience and the European Cubicin Outcomes Registry and Experience (2006–2009), 79 patients with MRSA DFI were identified and included in this analysis.
In the 74 evaluable patients, daptomycin was administered at a median dose of 4.8 mg/kg primarily every 24 hours (85.1%) and for a median of 15.0 days. Overall, 77.0% of the patients (57 of 74) received initial therapy with activity against MRSA; however, of patients receiving daptomycin as second-line therapy (n = 31), only 45.2% were treated with an antibiotic agent active against MRSA. The overall clinical success and treatment failure rates were 89.2% and 10.8%, respectively. Success with daptomycin therapy was higher in patients who had surgery and in those whose initial therapy was daptomycin. Eleven patients had 14 adverse events, two of which were possibly related to daptomycin use and led to discontinuation.
In a large real-world cohort of patients with MRSA DFI, daptomycin therapy was shown to be generally well tolerated and effective. The use of an anti-MRSA antibiotic agent should be considered when implementing first-line antibiotic drug therapy for DFI in countries where MRSA is common to avoid inappropriate empirical treatment and potential negative effects on outcomes.
Patients with diabetic neuropathy are subject to ulcerations that may be complicated by infection and gangrene, with subsequent risk of amputation. It is the job of the foot specialist to identify and manage these problems early to avoid the unfortunate complication of amputation regardless of the presenting condition of the patient’s limb. We shed light on the hypothesis that suggests that infection and gangrene in a diabetic patient aggravate the degree of ischemia (microvascular, macrovascular, or both) already present enough to endanger the viability of the surrounding tissues unless urgent drainage with decompression and debridement of the necrotic sloughs is performed, with consequent reduction of tissue pressure and improvement in circulation to the area. We present cases with severe infections leading to gangrene and ischemia, which were improved following surgical management with consequent improvement in tissue viability. In these cases, we demonstrate that immediate treatment of the wound despite the delayed presentation of the patients resulted in limb salvage with much less soft-tissue loss than expected before treatment. (J Am Podiatr Med Assoc 99(5): 454–458, 2009)
Background: Prediction of amputation would aid clinicians in the management of diabetic foot infections. We aimed to assess the predictive value of baseline and post-treatment levels of acute phase reactants in the outcome of patients with diabetic foot infections.
Methods: We collected data prospectively during minimum follow-up of 6 months in patients with infected diabetic foot ulcers hospitalized in Dokuz Eylul University Hospital between January 1, 2003, and January 1, 2008. After excluding patients who did not attend the hospital for follow-up visits regularly (n = 36), we analyzed data from 165 foot ulcer episodes.
Results: Limb ischemia and osteomyelitis were much more frequent in patients who underwent amputation. Wagner grade, which assesses ulcer depth and the presence of osteomyelitis or gangrene, was higher in patients who needed amputation. Ulcer size was slightly larger in the amputation group. Baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, white blood cell counts, and platelet counts were significantly elevated in patients who underwent amputation. Albumin levels were significantly suppressed in the amputation group. Univariate analysis showed that a 1-SD increase in baseline and post-treatment C-reactive protein levels, erythrocyte sedimentation rates, and white blood cell counts and a 1-SD decrease in post-treatment albumin levels were significantly associated with increased risk of amputation. Post-treatment C-reactive protein level was strongly associated with amputation risk.
Conclusions: Circulating levels of acute phase reactants were associated with amputation risk in diabetic foot infections. (J Am Podiatr Med Assoc 101(1): 1–6, 2011)
Background: We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections. It is widely believed that soft-tissue cultures are adequate in the determination of causative bacteria in patients with diabetic foot osteomyelitis. The culture results of specimens taken concurrently from soft-tissue and bone infections show that the former does not predict the latter with sufficient reliability. We sought to determine the similarity of pathogens isolated from soft tissue and bone in patients with diabetic foot infections.
Methods: Forty-five patients with diabetic foot infections were enrolled in the study. Patients had to have clinically suspected foot lesions of grade 3 or higher on the Wagner classification system. In patients with clinically suspected osteomyelitis, magnetic resonance imaging, scintigraphy, or histopathologic examination were performed. Bone and deep soft tissue specimens were obtained from all patients by open surgical procedures under aseptic conditions during debridement or amputation. The specimens were compared only with the other specimens taken from the same patients.
Results: The results of bone and soft-tissue cultures were identical in 49% (n = 22) of cases. In 11% (n = 5) of cases there were no common pathogens. In 29% (n = 13) of cases there were more pathogens in the soft-tissue specimens; these microorganisms included microbes isolated from bone cultures. In four patients (9%) with culture-positive soft-tissue specimens, bone culture specimens remained sterile. In one patient (2%) with culture-positive bone specimen, soft-tissue specimen remained sterile.
Conclusion: Culture specimens should be obtained from both the bone and the overlying deep soft tissue in patients with suspected osteomyelitis whose clinical conditions are suitable. The decision to administer antibiotic therapy should depend on these results. (J Am Podiatr Med Assoc 98(4): 290–295, 2008)
Selecting empirical therapy for a diabetic foot infection (DFI) requires knowing how likely infection with Pseudomonas aeruginosa is in a particular patient. We designed this study to define the risk factors associated with P aeruginosa in DFI.
We performed a preplanned microbiological subanalysis of data from a study assessing the effects of treatment with intralesional epidermal growth factor for diabetic foot wounds in patients in Turkey between January 1, 2012, and December 31, 2013. Patients were screened for risk factors, and the data of enrolled individuals were recorded in custom-designed patient data forms. Factors affecting P aeruginosa isolation were evaluated by univariate and multivariate logistic regression analyses, with statistical significance set at P < .05.
There were 174 patients enrolled in the main study. Statistical analysis was performed in 90 evaluable patients for whom we had microbiological assessments. Cultures were sterile in 19 patients, and 89 bacterial isolates were found in the other 71. The most frequently isolated bacteria were P aeruginosa (n = 23, 25.8%) and Staphylococcus aureus (n = 12, 13.5%). Previous lower-extremity amputation and a history of using active wound dressings were the only statistically significant independent risk factors for the isolation of P aeruginosa in these DFIs.
This retrospective study provides some information on risk factors for infection with this difficult pathogen in patients with DFI. We need prospective studies in various parts of the world to better define this issue.