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Revista de la Facultad de Medicina Humana
versión impresa ISSN 1814-5469versión On-line ISSN 2308-0531
Rev. Fac. Med. Hum. vol.24 no.2 Lima abr./jun. 2024 Epub 29-Abr-2024
http://dx.doi.org/10.25176/rfmh.v24i2.6518
Review Article
Global approach to the patient with diabetic foot: A review
1Universidad Autónoma de Barcelona. Barcelona, Spain.
2Instituto de Investigación en Ciencias Biomédicas, Universidad Ricardo Palma. Lima, Peru.
3Hospital Universitario Mútua de Terrassa. Barcelona, Spain.
4Parc Hospitalari Martí Julià. Girona, Spain.
5Hospital Universitario Son Espases. Palma de Mallorca, Spain.
6Hospital General de Medellín. Medellín, Colombia.
7Hospital General de Granollers. Barcelona, Spain.
8Hospital Universitario Germans Trias i Pujol. Badalona, Spain.
The review article highlights the importance of the sole of the foot in ambulation and its adaptation to human needs. It focuses on diabetic foot (DF), defined by signs, symptoms, or ulcers on the foot due to chronic complications of diabetes. DF affects approximately 25 % of patients with diabetes mellitus (DM), with ulcers that can lead to severe infections and risk of amputation. Managing DF is complex and requires a multidisciplinary approach. This article proposes a "Diabetic Foot Evaluation and Treatment System," applicable in various clinical settings, which classifies ulcers according to their depth and infection and provides clear treatment guidelines. The epidemiology of diabetic neuropathy (DN) is also discussed, highlighting its high prevalence and morbidity, and the need for adequate diagnosis and treatment. The article provides a detailed analysis of Charcot neuropathy, a severe complication of DF, including its causes and diagnostic methods. Furthermore, the importance of a multidisciplinary approach in the treatment of DF ulcers is emphasized to reduce amputations and improve patients' quality of life. DF infections and antibiotic therapy are also addressed, recommending the use of appropriate antibiotics according to the severity of the infection and the performance of precise microbiological cultures. Finally, a comprehensive view of DF management is presented, highlighting the importance of a multidisciplinary approach and proposing an effective evaluation and treatment system that can be implemented in various clinical contexts.
Keywords: Diabetic Foot; Diabetes Mellitus; Infections (Source: MeSH NLM).
INTRODUCTION
The foot, specifically the sole, is the body region that contacts the ground in both standing and walking due to our bipedal posture. A significant aspect of ambulation is largely the cultural evolution of our species. This important function allows us different modes of movement such as walking, running, and practicing sports, among others. For this, we have a series of proprioceptive and nociceptive receptors. These receptors allow us to interact with the ground and maintain balance in various modes of ambulation through what is known as Hilton's Law1.
There are evident homologies in the embryonic development2of the autopod observed around the sixth post-fertilization week of the hand and foot (hand and foot plates) and in the general anatomical organization of both structures (similarities between skeletal elements, intrinsic and extrinsic muscles, vessels, and nerves). However, the different functions determine the morphological adaptations observed in each.
DIABETIC FOOT
Diabetic Foot (DF) is understood as the “presence of signs, symptoms, or ulcers on the foot as a consequence of chronic diabetes complications”3. DF is one of the most prevalent complications in patients with diabetes mellitus (DM)4. In patients with DM, the risk of developing a foot ulcer can reach up to 25%5.
When a patient with DM develops an ulcer, several factors converge, such as changes in pressure points, deformities, or the use of inappropriate footwear, in addition to the total or partial loss of protective capacity (sensitivity), combined with underlying vegetative and vascular disorders. Consequently, the epidermal layer breaks down, and a lesion appears that can progress to deeper parts and reach the bone3,5, endangering the limb and even the patient’s life.
Managing foot lesions is usually complex and requires coordinated participation from different professionals. Studies have shown that a multidisciplinary approach is the most effective way to treat these patients and reduce the number of amputations6-8. Therefore, we propose our “Diabetic Foot Evaluation and Treatment System” to facilitate this approach9.
This review aims to provide a comprehensive overview of DF management, highlighting the importance of a multidisciplinary approach and presenting an easy-to-use evaluation and treatment system applicable in any work setting, from primary care to hospitals or emergency services. Additionally, limitations and possible biases in the reviewed studies are discussed to provide a more balanced and critical view of the literature.
EPIDEMIOLOGY OF DIABETIC NEUROPATHY
The prevalence of diabetic neuropathy (DN) varies according to the series consulted, depending on the diagnostic methodology, criteria used, and disease duration in the studied population, making it difficult to compare prevalence rates across different regions. In this context, Pirart J. evaluated 4,400 patients with diabetes mellitus (DM) over 25 years of follow-up10-13. In this study, neuropathy was defined as a decrease in foot sensitivity and a decrease or absence of the Achilles reflex. The onset of neuropathy positively correlated with the duration of DM, and at 25 years, 50% of patients had developed neuropathy.
In Spain, Mundet et al. evaluated the prevalence and incidence of macro and microvascular complications over ten years of follow-up in a prospective population-based study that included 317 patients with type 2 DM, finding a DN prevalence of 26.8% [19.3-30.2] at the end of the study14. In Latin America and the Caribbean, a systematic review and meta-analysis of 29 studies from eight countries in the region reported an estimated DN prevalence of 46.5% (95% CI: 38.0-55.0) with significant heterogeneity (I² = 98.2%; p < 0.01), finding an increasing trend in cumulative DN prevalence over time. In this same study, four investigations in Peru with a sample size of 874 patients reported a DN prevalence of 52%15.
However, it is important to note that up to 50% of patients with DN may be asymptomatic, increasing the gap of underdiagnosis of this complication. According to Longa J. in his study "Attitudes of Physicians Towards the Management of Diabetic Neuropathy in Public and Private Health Facilities, 2023", of 143 physicians surveyed, 80.5% reported relying only on symptoms and signs referred by the patient to diagnose DN16.
The high rate of DN produces substantial morbidity, including disability generated by painful neuropathic symptoms and the underlying neurological deficit, which have a significant impact on these patients' quality of life and result in manifestations such as ataxia, weakness, falls, fractures, lacerations, cranial trauma, recurrent lower limb infections, ulcerations, and subsequent amputations. Patients diagnosed with diabetic foot (DF) occupy more hospital beds than those with other diabetic complications17. The cumulative risk of lower limb amputation in one study was 11% 25 years after the DM diagnosis18.
Risk factors for DN studied vary according to the strength of association. Those with a very strong association include diabetes duration, hyperglycemia, and age. Those with a strong association include prediabetes, height, hypertension, obesity, metabolic syndrome, oxidative stress, vitamin D deficiency, genetic factors, subclinical inflammation, and low physical activity. Those with a moderate association include glycemic variability, dyslipidemia, smoking, insulin resistance, alcohol consumption, hypoinsulinemia, platelet activation, and growth factor depletion19.
DIAGNOSIS OF DIABETIC NEUROPATHY
Screening for diabetic neuropathy (DN) should be performed in patients with type 2 diabetes mellitus (DM2) at the time of diagnosis. In patients with type 1 diabetes mellitus (DM1), screening should be performed five years after diagnosis. Additionally, prediabetic patients should be included in this screening if they present neuropathic symptoms. If the initial examination is negative, it should be repeated annually20.
The diagnosis of DN is based on three fundamental pillars: evaluation of symptoms, signs, and, in some cases, the performance of neurophysiological and/or morphometric tests. Symptoms can be classified as positive or negative, depending on whether there is a gain or loss of function, resulting from the maladaptive response to somatosensory nervous system damage or pathology. The first group of symptoms (positive) includes paresthesias, spontaneous pain (burning, searing, stabbing, etc.), or evoked pain (hyperalgesia or allodynia). The second group (negative) can include sensory deficits such as hypoesthesia, anesthesia, hypoalgesia, or analgesia. These clinical manifestations can coexist or alternate throughout the natural history of DN.
Systematic evaluation of symptoms can be conducted through validated questionnaires, such as the Michigan Neuropathy Screening Instrument (MNSI), the Utah Early Neuropathy Scale (UENS), the United Kingdom Screening Test, and the Total Symptom Score (TSS). From a pathophysiological perspective, the involvement of thin nerve fibers (C or Aδ), characterized by being unmyelinated or finely myelinated, clinically manifests as burning pain, electric shocks, or stabbing pain. Autonomic symptoms can also occur since these fibers are responsible for thermoalgesic sensitivity and autonomic function.
As for the thick fibers (Aα or Aα/β), their involvement can cause numbness-type pain, a feeling of walking on cotton, difficulty performing fine tasks like turning book pages or buttoning a shirt, and balance or musculoskeletal trophism alterations, occasionally leading to an inability to stand on the tip of the toes or heels. These myelinated fibers control muscle function and tactile, vibratory, and proprioceptive sensitivity.
In physical examination, signs such as dry skin, fissures, plantar hyperkeratosis, ulcers, overlapping or rigid toes, hammer or claw toes, deformities, bony prominences, Charcot neuroarthropathy, and atrophy of the interosseous muscles may be found. Clinical evaluation of the different types of nerve fibers depends on the availability of instrumental resources, and for this purpose, the Semmes-Weinstein 10 g monofilament, the 128 Hz tuning fork, and the reflex hammer can be used to assess thick fibers, while the thermal bar and pinprick are used to assess thin fibers.
It is important to note that none of these tests alone achieve the sensitivity and specificity needed for DN diagnosis, so combining two or more of them is necessary to confirm the diagnosis. Additionally, there is no standardization of the evaluation methodology, which can hinder early neuropathy detection21.
Neurophysiological and/or morphometric tests are important tools but are limited in use due to their complexity and limited availability in routine medical practice. For thick fiber evaluation, nerve conduction velocity (NCV) studies for Aβ fibers and the DPNCheck, which evaluates Aβ fibers of the sural nerve with good sensitivity (92-95%) compared to NCV, are used. For thin fiber evaluation, skin biopsy can be used to assess C fibers by quantifying intraepidermal nerve fiber density (IENFD), considered the gold standard for this evaluation and capable of detecting early changes. Corneal confocal microscopy (CCM) also allows for evaluating Aδ and C fibers, being a non-invasive, reproducible, fast, and objective method.
Autonomic tests like the Neuropad, Sudoscan, and QSART are useful for assessing C fibers responsible for autonomic functions, including sudomotor functions. While these tools have different sensitivities and specificities, they are useful for this purpose. Quantitative sensory testing (QST) methods allow for the evaluation of both thin (Aδ and C) and thick (Aβ) fibers with good reproducibility21.
CHARCOT NEUROPATHY
Charcot neuroarthropathy has a multifactorial etiology, with two main theories proposed to explain its development: the neurotraumatic and neurovascular theories. The neurotraumatic theory suggests that poor pain perception in diabetic patients causes repetitive traumas to go undetected, resulting in multiple fractures and collapse of the foot’s bone structure. On the other hand, the neurovascular theory postulates that bone destruction is due to a hypervascular state caused by sympathetic nerve alteration, leading to loss of vasomotor control. This condition causes bone mineral leaching, resulting in osteopenia or osteoporosis, making the tissue more susceptible to low-magnitude fractures.
The inflammatory process is localized and persistent, without systemic repercussions, characterized by increased vascular flow and elevated levels of pro-inflammatory cytokines. This disrupts the RANKL (receptor activator of nuclear factor kappa B ligand) system, increasing the number and activity of osteoclasts, thus enhancing bone resorption. Molecules like calcitonin gene-related peptide, which normally stabilize the capsuloligamentous extracellular matrix, are released less in the context of diabetic foot, promoting an environment of biomechanical instability and generating pressure zones22. Additionally, healing is compromised due to reduced macrophage activity and angiogenesis, increasing infection risk due to a diminished immune response23.
The diagnosis of Charcot neuroarthropathy is primarily clinical. Semiological signs include inflammation (phlogosis) and edema. It is crucial to investigate neuropathic changes in the anamnesis and objectively assess temperature differences greater than 2°C compared to the contralateral limb. In advanced stages, inflammatory signs become less noticeable, with bone prominences and foot deformities predominating, especially in the hindfoot, which may include claw toes and dry skin (xerotic) due to loss of moisture24,25.
Laboratory tests such as bone-specific alkaline phosphatase and type 1 collagen carboxy-terminal telopeptide levels are useful for quantifying bone resorption in acute phases and decrease as chronicity sets in. Acute phase reactants, such as erythrocyte sedimentation rates below 70 mm/h, indicate a more neuroarthropathic than infectious process. Load-bearing radiographs (posteroanterior and lateral) with oblique views allow for observing deformities and classifying the disease according to the Eichenholtz classification26. It is important to evaluate deformities in the sagittal plane, considering inclinations at the Chopart level and the pitch of the calcaneal and fifth metatarsal angles.
Table 1. Eichenholtz Classification.
Stage | Description |
Stage 1 | Acute phase: inflammation. Subtle dislocations, changes in calcaneal inclination with concomitant alteration of the talus-first metatarsal angle. Bone fragmentation and significant soft tissue edema are observed. |
Stage 2 | Coalescence phase (subacute): Reduction in inflammation, especially in temperature. Remodeling and reparative processes can be observed. |
Stage 3 | Consolidation phase (chronic): Complete resolution of inflammation, consolidation of fractures, and ossification, in many cases heterotopic. |
Taken from Hastings et al.(26)
In the acute phase, magnetic resonance imaging (MRI) can reveal subchondral bone marrow edema and microfractures, facilitating the monitoring of the clinical process. Positron emission tomography/computed tomography (PET/CT) shows increased metabolism in the affected regions, allowing for a more sensitive evaluation. Differentiating Charcot arthropathy from an infectious or inflammatory process can be challenging, as they may coexist. Therefore, we propose an algorithm that is part of the diagnosis, evaluation, and treatment system (Figure 1).
It is recommended to use conservative treatment whenever possible. Offloading is essential and can be achieved through initial total contact casting for six to eight weeks, with changes every two weeks, until the inflammatory state is reduced, allowing for the use of adapted orthopedic footwear. This process generally takes a minimum of six months. Except for the management of metabolic and comorbid conditions in DM patients, there is no evidence of the effectiveness of specific medications for the treatment of Charcot arthropathy27.
The goal of treatment is to achieve a plantigrade foot with an even distribution of plantar pressures. Maintaining this position can heal up to 50% of neuropathic ulcers without the need for surgical interventions, allowing the patient to return to a functional level similar to the previous one, prevent ulcerations, and reduce long-term medical costs.
Chronic deformities are a significant challenge to correct due to the morphological alteration and the generation of prominent ulcers. A holistic evaluation of the patient is essential, including infection history, previous cultures, treatments, and imaging studies to determine the involved joints. The appropriate fixation material should be planned, and proper cultures taken to use antimicrobials based on the results3,27. Interventions may include external fixators, screw and plate fixations, exostectomies, myotendinous transfers, and lengthenings, which can be transitional until achieving a definitive construct28.
PERIPHERAL ARTERIOPATHY
Macrovascular disease in patients with diabetes mellitus (DM) is characterized by being a diffuse atheromatous process, affecting not only the arteries of the lower extremities but also the coronary and carotid arteries. The involvement of the arterial territory in peripheral arterial disease (PAD) varies according to the presence of DM. In patients without DM, it preferably affects the aortoiliac and femoropopliteal territory. In contrast, PAD in patients with DM is characterized by more frequent involvement of the tibial and inframalleolar arteries, specifically affecting the infragenicular territory and the area below the ankle.
DM is the most common cause of non-traumatic lower limb amputation. Seventy-five percent of lower limb amputations in our setting are performed on patients with DM 29. In fact, amputation is 15 to 40 times more frequent in patients with DM than in those without this condition 30. Approximately 85% of amputations in patients with DM are preceded by a foot ulcer. Between 7% and 20% of patients with DM who develop a foot ulcer will eventually require a more or less extensive limb amputation 31. Additionally, patients with DM have twice the risk of a second amputation if they have a history of a previous amputation compared to patients without DM.
Major amputations are associated with increased mortality in patients with DM. Short-term mortality is approximately 10%, increasing to 30% at one year, 50% at three years, and 70% at five years 32. Regarding the prevalence of PAD in patients with diabetic foot (DF), current data shows it is present in approximately half of the patients.
The presence of PAD in a patient with DF increases the risk of ulcer infection and complicates its healing 33. This phenomenon is partly due to the difficulty in the delivery of nutrients and oxygen to the tissue, as well as poor penetration of the antibiotic into the infected tissue. Regarding the costs associated with the care of these patients, it should be noted that the presence of an infected ulcer in a patient with PAD multiplies the costs fourfold compared to patients with a foot ulcer without PAD or infection. This increase is mainly due to hospitalization expenses, the use of antibiotics, amputations, and other surgical procedures 34.
Finally, it is important to mention that the treatment of DF ischemia is still suboptimal, according to the data described in the Eurodiale study. This study, which involved fourteen hospital centers, aimed to analyze the characteristics of 1,229 patients with DM who had a foot ulcer. Only 40% of patients with severe ischemia underwent angiography, and only 43% with critical ischemia underwent a revascularization procedure 34.
COMPREHENSIVE MANAGEMENT OF DIABETIC PATIENTS WITH FOOT ULCERS
The management of ulcers in diabetic patients is complex due to the need for intervention from multiple professionals. This complexity lies in the coordinated execution of the proposed treatment. To facilitate this multidisciplinary approach, we propose using the "Diabetic Foot Evaluation and Treatment System," published in November 2023 in the journal Foot and Ankle Research.
This system (Table 2) consists of a main table that evaluates two fixed variables: the presence of infection and the depth of the ulcer, classifying them into five grades (from 0 to 4). Grade 0 excludes Charcot foot or underlying infections without the presence of an ulcer; grade 1 encompasses superficial ulcers (epidermis/dermis) without signs of infection; grade 2 includes ulcers that reach the subcutaneous tissue with signs of superficial infection; grade 3 comprises deep ulcers that reach the subcutaneous tissue or bone, with signs of deep but localized infection; and grade 4 considers deep ulcers as in grade 3, but also presents critical ischemia, areas of necrosis, and/or systemic involvement. When an ulcer is ischemic in nature, it is considered and treated as an additional grade due to the significantly worsened prognosis.
Table 2 Proposed evaluation and treatment system.
Evaluation and Treatment System for Diabetic Foot | |||||
Ulcer Grade | 0 | 1 | 2 | 3 | 4 |
CHARACTERISTICS Depth Infection? | NO ULCER Hot foot, edema, erythema. DISMISS | EPIDERMIS/DERMIS SIGNS OF ISCHEMIA** No | GI+ SUBCUTANEOUS TISSUE SIGNS OF ISCHEMIA** Superficial | GII+ FASCIA/MUSCLE/BONE SIGNS OF ISCHEMIA** Deep/localized | GIII ISCHEMIA? YES/NO NECROTIC AREAS Systemic involvement |
Evaluation | Screening/ Thermometry Neuroarthropathy? Nuclear Medicine? | Neuroischemic screening | Neuroischemic screening Microbiological culture Discard osteomyelitis | Neuroischemic screening Microbiological culture Discard osteomyelitis | Neuroischemic screening Microbiological culture Discard osteomyelitis |
Treatment | If suspected of Charcot neuroarthropathy: immobilize: boot or synthetic cast Surgery? | Offloading Topical treatment | Offloading Topical treatment Oral antibiotics | Debridement, surgery Oral/IV antibiotics Topical treatment Offloading Relative rest | Debridement and/or revascularization IV antibiotics Topical treatment Absolute rest |
Care level Patient education | Primary care/ UPD/ Hospital Review | Primary care Review | Primary care/ UPD Review | UPD/ Hospital Review | Hospital/UPD |
**SIGNS OF ISCHEMIA**: Consider as an additional grade |
Additionally, the system includes nine supplementary tables or algorithms that address different aspects of DF management: diagnosis of Charcot neuroarthropathy (Figure 1), neuroischemic screening (Figure 2), diagnosis of osteomyelitis (Figure 3), obtaining samples for microbiological culture (Figure 4), microorganisms to consider (Figure 5), oral antibiotics (Figure 6), topical treatment (Figure 7), offloading systems (Figure 8), and surgical techniques (Figure 9). Each of these algorithms provides guidelines for the required examination, differential diagnosis, and the most appropriate treatment for each situation. The implementation of this system allows for a more structured and effective management of ulcers in diabetic patients, optimizing collaboration among the various specialists involved.
INFECTIONS AND ANTIBIOTIC THERAPY IN DIABETIC FOOT
Infection in diabetic patients can be a serious complication. Although most infections are superficial, up to 25% can extend to deeper tissues, even affecting the bone. It is important to remember that an infected foot ulcer precedes 60% of amputations35. Antibiotic treatment of infections in the diabetic foot requires a deep understanding of the lesion's pathogenesis, with explicit mention of the biofilm and the microorganisms involved. This is essential for selecting the appropriate antibiotic based on the microorganism's sensitivity and various pharmacokinetic characteristics.
Bone infection, or osteomyelitis, is a common complication of diabetic foot ulcers. To rule out contiguous infection, the bone contact test is performed. Any exposed bone at the base of an ulcer, whether visible or that can be contacted by inserting a sterile blunt-tipped probe, has a high probability of being infected, with a specificity of 83% and a sensitivity of 87%36. The following algorithm (Figure 3) assists in the correct interpretation of the bone contact test and the precise diagnosis of osteomyelitis.
BIOFILM AND MICROBIOLOGICAL CULTURE
The presence of biofilm in diabetic foot ulcers complicates antibiotic therapy. The biofilm, a biofilm generated by the interaction of cells covering the ulcer and physicochemical and bacterial factors, hinders the penetration and activity of antibiotics, as well as the isolation of the microorganisms responsible for the infection. This latter issue, with poorly collected samples, makes it difficult to differentiate between contamination and infection37. To etiologically identify the responsible microorganism, it is mandatory to clean and debride the wound before obtaining the sample. This can be obtained by scraping the ulcer with a scalpel, curettage, or surface biopsy. Aspiration of purulent secretions with a sterile needle and syringe can also be useful. All samples should be promptly placed in a sterile container or appropriate medium and sent to the laboratory for Gram staining and aerobic and anaerobic culture38.
On the contrary, non-infected ulcers should not be cultured, nor should samples be obtained without prior cleaning or debridement, or by swabbing the wound or purulent secretions. Table 3 presents the microorganisms responsible for diabetic foot infection according to various series35,39-41.
Tabla 3 . Microorganismos responsables de la infección
GRAM POSITIVE | ||
S. aureus | 72 (30) | |
S. coagulasa negativos | 4 (1.7) | |
Enterococcus spp | 8 (3.3) | |
Streptococcus pyogenes | 4 (1.7) | |
GRAM NEGATIVE | ||
E. coli | 24 (10) | |
Klebsiella pneumoniae | 22 (9.2) | |
Enterobacter spp | 22 (9.2) | |
Proteus spp | ||
Pseudomonas aeruginosa | 28 (11.7) | |
Acinetobacter spp | 12 (5.2) | |
S. maltophilia | 2 (0.8) | |
ANAEROBES | 21 (2) | |
OTHERS | (>5.2) |
Adapted from the references(35,39-41).
However, depending on the characteristics of the wound, certain microorganisms must be particularly taken into account (Table 4).
Table 4 Wound characteristics and responsible microorganisms
Type of wound | Microorganisms responsible for infection |
---|---|
Cellulitis or open skin wound | S. aureus / β-hemolytic Streptococcus |
Infected ulcer (NO previous antibiotics) | S. aureus / β-hemolytic Streptococcus |
Chronically infected ulcer (previous antibiotics) | S. aureus / β-hemolytic Streptococcus / Enterobacteriaceae |
Macerated ulcer | Pseudomonas aeruginosa |
Long-standing ulcers with previous antibiotics | Aerobic Gram-positive cocci, Enterobacteriaceae, Pseudomonas spp, and other non-fermenting Gram-negative bacilli |
Foul-smelling, extensive necrosis, or gangrene | Polymicrobial flora: Gram-positive cocci, Enterobacteriaceae, non-fermenting Gram-negative bacilli, anaerobes |
Adapted from the references(35,39-41).
Depending on the severity of the ulcer, according to the criteria of our classification system, the microorganisms indicated in Figure 5 should be considered.
As shown in Figure 5, Gram-positive cocci are usually present in all stages of severity, so it will always be necessary to cover them with appropriate antibiotics. Anaerobes, on the other hand, are observed in severe ulcers and always associated with other microorganisms. In these cases, broad-spectrum antibiotic treatment is required, also considering the possibility of multi-resistant enterobacteria producing extended-spectrum beta-lactamases.
ANTIBIOTIC THERAPY
Before administering antibiotics, it is crucial to consider several characteristics inherent to the microorganism and the pharmacokinetics of the antibiotic. This includes the sensitivity of the microorganism to the tested antibiotics according to the antibiogram, the bioavailability of the antibiotic when administered orally, and its volume of distribution42.
Oral bioavailability is a fundamental characteristic for selecting effective antibiotics via this route. Some antibiotics, such as fluoroquinolones, have a bioavailability close to 100%, while amoxicillin does not reach 70%. Both are useful in diabetic foot, but doses must be adjusted appropriately43. The volume of distribution is also important, as some antibiotics are preferentially distributed in the vascular compartment, reaching the interstitium and the cellular compartment in low concentrations. In diabetic foot, antibiotics with a high volume of distribution are preferred to ensure they adequately reach the site of infection44.
Table 6 presents a scheme detailing the use and considerations of oral antibiotics in the treatment of infections in diabetic foot. The Figure is divided into several sections addressing critical aspects of antibiotic therapy, such as antibiotic selection, oral bioavailability, and volume of distribution.
Table 6 Oral antibiotic therapy for diabetic foot infections.
Antibiotic | Microorganisms | Dose (mg) | Dose interval (hours) | Bioavailability (%) | Distribution (L/kg) | Renal elimination | Side effects |
---|---|---|---|---|---|---|---|
Amoxicillin | GP/GN | 500-1000 | 8 | 60 | 0.2 | No | Gastrointestinal |
Amox-Clavulanic | GP/GN/AN | 875 | 8 | 60 | 0.2 | No | Gastrointestinal |
Levofloxacin | GP/GN | 750 | 24 | >90 | 1.5 | Yes | Tendinopathy, Qt, CNS |
Moxifloxacin | GP/GN | 400 | 24 | >90 | 2.0 | No | Qt, CNS |
Clindamycin | GP/AN | 300-450 | 8 | >90 | 1.1 | No | Gastrointestinal, CD |
Cotrimoxazole | GP/GN | 160-800 | 12 | >90 | 1.8 | Yes | Nephrotoxicity, AL |
Linezolid | GP | 600 | 12 | 100 | 0.7 | No | Hematological |
Doxycycline | GP | 100 | 12 | >90 | 0.7 | Yes | Gastrointestinal |
Metronidazole | AN | 500 | 8 | >90 | 0.8 | No | Gastrointestinal, CNS |
Rifampicin | GP | 600 | 24 | >90 | 1.6 | No | Hepatotoxicity |
GP: Gram positive. GN: Gram negative. AN: Anaerobes. Qt: QT Interval prolongation. CNS: Central Nervous System. CD: Clostridioides difficile-associated diarrhea. AL: Allergic reactions. H: Hepatotoxicity. HE: Hematological effects.
Taken from references(42-44)
DURATION OF ANTIBIOTIC TREATMENT
The duration of antibiotic treatment varies according to the severity of the infection. Most ulcers will be sterilized with one to two weeks of oral treatment. In more complicated cases, treatment can start with intravenous antibiotics followed by oral antibiotics to complete two weeks. Suspected osteomyelitis requires treatments of three to four weeks, and after debridement, if viable bone remains, the treatment should continue for approximately three months. In any case, the clinical evolution will determine the exact duration of the antibiotic treatment31,42.
TOPICAL TREATMENT
In recent years, new technologies and products have been developed to accelerate the healing of foot ulcers in patients with diabetes. Currently, there is a wide range of products and devices for topical treatment. The choice of the appropriate product depends on several factors, including the depth and extent of the ulcer, the presence of infection and/or necrotic tissue, and the degree of exudation45. It is important to consider that the disease itself can slow down the healing process due to the presence of vasculopathy, neuropathy, humoral immunodeficiency factors, smoking, among others3.
In ulcers located on the plantar surface of the foot, where the stratum corneum is thicker, the use of adhesive dressings is not recommended to avoid maceration. If the degree of exudation is significant or a graft is required, negative pressure therapy may be an effective therapeutic option46. Figure 7 provides guidance on topical treatment based on the grade of the ulcer.
OFFLOADING SYSTEMS
Offloading is essential for the prevention or treatment of pressure areas or active ulcers. Various materials and systems are available for this purpose, requiring knowledge in biomechanics and skills for proper fabrication and application. The general objective of offloading, whether provisional (adhesive felt, plastic cast, functional orthosis) or definitive (plantar support, silicone orthosis, special footwear), is to evenly distribute the forces and pressures acting on the foot, protecting healthy areas and isolating ulcerated or susceptible areas3.
Structural alterations of the foot, along with high plantar pressure, are major factors influencing the formation of plantar ulcers in diabetic patients47. For the fabrication of provisional offloading systems, adhesive felt and polyurethane bandages are preferably used. The functional orthosis (Walker) can be used in combination with adhesive felt for offloading or to control edema and prevent deformities in patients with Charcot neuroarthropathy in phase 0-1 or suspected48.
The use of plantar supports is indicated when the ulcer is healed or as a prevention for areas of high pressure that, if not corrected, could become ulcers, as well as to prevent recurrences3,49. Figure 8 presents a detailed scheme of the different offloading systems used in the management of diabetic foot ulcers. These systems are crucial for reducing pressure on the affected areas and promoting healing.
SURGICAL TREATMENT
Surgery is often necessary in diabetic patients to address a variety of issues such as ulcers, infections, and severe deformities. Various surgical techniques are used to correct deformities, eliminate areas of high pressure, improve foot support, heal or prevent ulcers, revascularize the limb, or perform some type of amputation50(Figure 9).
The fundamental principle of surgical interventions in diabetic foot is osteotomies. These interventions allow for the correction of bone deformities that can contribute to ulcer formation. Surgery in these cases involves cutting and repositioning bones to relieve pressure and improve load distribution on the foot51. Osteotomies are especially indicated in neuropathic ulcers without underlying osteomyelitis that do not respond to conventional treatment.
Among the most common osteotomies are: the base osteotomy of the first metatarsal52, indicated in cases of hyperpressure on the head of the first metatarsal caused by cavus feet, adducted feet, posterior leg compartment muscle shortening, or biomechanical alterations; the base osteotomy of the proximal phalanx of the first toe3, indicated for treating ulcers located on the plantar area of the first toe's interphalangeal joint; and the distal oblique osteotomy of the lesser metatarsals (second to fifth)53, indicated for ulcers located in the plantar metatarsal area without the presence of osteomyelitis. The decision on the number and type of osteotomies is based on clinical and radiological criteria, considering the morphology of the metatarsal formula and the ulcer location, with the Leventen formula recommended to guide these interventions3.
SURGICAL TECHNIQUES
When an infected foot is found, the most common surgical techniques initially include surgical debridement, which consists of removing dead or infected tissue around an ulcer. This procedure not only cleans the wound and promotes healing but also allows for sample collection for study and microbiological culture. Debridement may need to be repeated as necessary3,50,54.
Once debridement is performed, various surgical techniques can be carried out depending on the specific problem. Partial or complete exostectomies allow for skin closure and prevent ulcer recurrence3,55. In cases of joint instability or major deformities, arthrodesis, which involves the fusion of a joint, is performed. By fusing a joint, its natural mobility is eliminated, thereby reducing the risk of new ulcer formation. Arthrodesis can be performed using internal fixation with plates and screws or external fixation56, known as osteotaxis.
Due to the biological complexity of diabetic patients, arthrodesis is not always effective and may result in fibrous arthroplasty. Although not the ideal scenario, fibrous arthroplasty provides relative stability compatible with ambulation and a plantigrade foot57. To avoid this scenario, current trends favor performing arthrodesis and osteosynthesis with "superconstruct" techniques, which use a greater amount of osteosynthesis material and screws to ensure more robust and durable fixation58.
Revascularization techniques and indications
In situations where the results of other interventions are unsatisfactory and the evolution is unfavorable, compromising the limb or the patient's life59, amputations are resorted to. In severe cases, where ulcers or infections are extensive and unresponsive to other treatments, amputation may be the only option to prevent infection spread and save the patient's life. Additionally, in cases where the arterial system is obstructed, revascularization of the diabetic foot may be necessary to restore blood flow. This may include techniques such as angioplasty, stent placement, or vascular bypass3.
Reconstruction techniques: Plastic surgery
Regarding plastic surgery, various techniques such as grafts, flaps, and artificial dermis are useful for ulcer coverage in patients with diabetic foot. Reconstruction of the distal lower extremity is a surgical challenge, especially in those cases with a high risk of complications such as diabetes or advanced vasculopathy. Several types of local and regional flaps have been described, such as the sural flap or the extensor digitorum flap. However, the main problem lies in the lack of reliability of their vascularization, especially in patients with underlying vasculopathy or loss of tissue quality due to chronic pathologies or the high thickness of the flap, creating contour defects60.
FINAL RECOMMENDATIONS FOR THE DIAGNOSIS OF DIABETIC FOOT
The diagnosis of diabetic foot infection should be primarily based on clinical criteria.
A visible bone with a positive bone test is highly suggestive of osteitis/osteomyelitis.
It is crucial to clean and debride before culturing.
Biopsy is the most cost-effective procedure from a microbiological standpoint.
For outpatient treatment, use antibiotics with good oral bioavailability and good compartmental distribution.
An antibiotic window is recommended in case of poor evolution or recurrence (do not treat while selecting microorganisms).
The microbiological documentation of diabetic foot infections is very helpful for antibiotic prescription, always accompanied by clinical information (especially appearance and evolution).
The Microbiology laboratory should know, inform, and detect local bacterial resistance patterns.
Gram staining as a rapid test provides valuable information. The quantification of cultures has not shown added value.
FINAL RECOMMENDATIONS FOR THE TREATMENT OF DIABETIC FOOT
The treatment of diabetic foot infections should include empirical antibiotics covering Staphylococcus aureus (SSA, MRSA, CA-MRSA) and Streptococcus spp.
It is essential to clean and debride the wound before taking samples for microbiological culture.
Use antibiotics with good oral bioavailability and adequate compartmental distribution for outpatient treatment.
In case of poor evolution or recurrence, an antibiotic window is recommended instead of continuously adjusting the treatment.
Select products for topical treatment according to the ulcer's depth, extent, presence of infection or necrotic tissue, and exudate level.
Implement offloading systems, such as adhesive felt, polyurethane bandages, and functional orthoses, to reduce pressure on the affected areas.
Use plantar supports to prevent ulcer recurrence once healed and correct areas of hyperpressure.
Perform surgical debridement to remove dead or infected tissue and promote healing, allowing sample collection for microbiological culture.
Consider performing partial or complete exostectomies to allow skin closure and prevent recurrence.
Employ arthrodesis to fuse joints in cases of instability or severe deformities, using internal or external fixation as needed.
CONCLUSIONS
Every patient diagnosed with diabetic foot should receive treatment through a multidisciplinary team7-9,61. It is essential to coordinate the different specialties with a common goal and establish a link between all specialists. The "System for the Evaluation and Treatment of Diabetic Foot" brings together in one document all the necessary variables for the proper management of these patients. This system can be used in any work setting, from primary care and diabetic foot units to hospitals and emergency services. Its implementation simplifies multidisciplinary management, facilitates collaboration among professionals, and significantly contributes to reducing the number of amputations. The results obtained over more than 20 years support its effectiveness and usefulness in clinical practice.
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8Article published by the Journal of the faculty of Human Medicine of the Ricardo Palma University. It is an open access article, distributed under the terms of the Creatvie Commons license: Creative Commons Attribution 4.0 International, CC BY 4.0 (https://creativecommons.org/licenses/by/1.0/), that allows non-commercial use, distribution and reproduction in any medium, provided that the original work is duly cited. For commercial use, please contact revista.medicina@urp.edu.pe.
Received: January 05, 2024; Accepted: April 29, 2024