Diabetes Mellitus is one of the leading causes of foot infections because of complications associated with poor blood circulation and loss of feeling from nerve damage. These factors contribute to an increased likelihood of infections, of which cellulitis is but a mild manifestation to chronic osteomyelitis. The immune access as well as the antibiotics are limited in their effectiveness by microvascular and macrovascular complications. Diabetic patients can also get severe infections such as fetid foot which comprises the soft tissue and bone, and gangrene derived from peripheral vascular disease. The organisms responsible for these infections are generally like those found in non-diabetic individuals although gas gangrene is less frequently encountered. Overall, foot infections in diabetics are more severe and require a longer period to heal. Staging is most appropriate where chronic osteomyelitis is likely to require operation.

Diabetic foot infections rank among the most common types of skeletal and soft-tissue infections affecting the global populace. These infections occur concurrently with the prevalence of the disease in the different ethnic groups targeting the elderly most. The rate of infected individuals does not differ widely between males and females.

Although the death from diabetic foot infections is comparatively low, it is not impossible under some conditions. The incidences of the highest risk infection rates are recorded in patients with chronic osteomyelitis and those with acute necrotizing soft-tissue infection.

A prospective cohort study by Lynar et al also noted that patients who are old and those on hemodialysis are more vulnerable to high mortality risks. The one-year cumulative mortality risk in patients on hemodialysis was identified as being 24.5%.

In chronic osteomyelitis, there is usually the presence of a sequestrum and involucrum, which are infected areas of the bone that are not supplied with blood. Bacteremia can be associated with cellulitis, skin and soft tissue infections and acute osteomyelitis. If chronic osteomyelitis is left untreated for an extended period, the disease may result in new complications like amyloidosis or squamous cell carcinoma within the areas where there is drainage through ulcers. However, bacteremia and septic shock are not the usual complications of chronic osteomyelitis. Previous studies have identified that in Staphylococcus aureus, the prophage ROSA-like can slow the motion or even prevent the bacterium of infecting diabetic foot ulcers and hindering replication within osteoblasts decreasing resulting cellular damage in these lesions.

Diabetes involves the microvasculature of the extremities, causing a higher susceptibility to skin, soft tissue, and bone infections. Trauma or ill-fitting shoes worsen the risk by diminishing blood flow even more in the limbs. Diabetes likewise aggravates macrovascular conditions such as atherosclerosis; however, it is microvascular injury that is at the root of diabetic foot infections. Diabetic neuropathy could not feel injury hence the high risk for infections. Historically, S. aureus is a typical agent, but others such as P. multocida or, rather seldom, group B streptococci also can be the causes of infection. More severe infections can be caused by other gas producing bacteria and can lead to such fatal diseases as necrotizing fasciitis. In acute osteomyelitis, the most common pathogens isolated are Staphylococcus aureus, which often results from trauma; the chronic osteomyelitis is associated with a wide range of infecting organisms, including MRSA and Pseudomonas.

The outcome of cellulitis, skin and soft tissue infections, and acute osteomyelitis in a good measure is influenced by the management which includes antibiotic therapy as well as surgical intervention such as debridement. In chronic osteomyelitis, prognosis depends on the state of circulation in the affected limb, effectiveness of surgical treatment.

Investigating 248 diabetic patients with foot ulcer, a German team observed significant peripheral artery disease and renal insufficiency as independent predictors of major lower limb amputation at long term. In their study, Chammas et al. identified that ischemic heart disease is responsible for the largest percentage of premature mortality, with 62.5% of the deaths incurred by the patients with diabetic foot ulcers.

Age group

It has been notified that diabetic foot Infections are common in middle aged and elderly patients who are above fifty years of age. Higher incidence is observed in patients with longer-standing diabetes (usually for more than 10 years).

Cellulitis: Red tender skin lesions located in the lower limbs; can have swollen lymphatics (group A streptococcal infection). Pustules may point towards Staphylococcus aureus. No deep ulcers or exudate.

Deep-Skin and Soft-Tissue Infections: Inflammation with pain in the legs or feet; sometimes accompanied by a bad odor if caused by the integration of anaerobic bacteria. Worsening pain and crunching sound may suggest a diagnosis of gas gangrene, or compartment syndrome. Acute Osteomyelitis: Localized bone pain only, if there is no neuropathy involved); symptoms persist for 10-14 days. Fever and adenopathy are normally not seen in this condition.

Peripheral neuropathy

Peripheral vascular disease

Chronic kidney disease

Ischemic heart disease

Obesity

Early stages: Localized cellulitis; erythema, oedema and rubor are manifestations without pain because of neuropathy.

Intermediate: Symptoms become localized to deeper structures, where tissues and bones can become infected and ulcerative tissue begins to slough as well as foul smelling discharge and necrosis.

Advanced/acute: It becomes chronic or severe complicated infections with osteomyelitis or necrotizing fasciitis. In severe cases, this leads to gangrene, progress to general symptoms of the infection (fever, chills) and sepsis.

Chronic infections: Patients who present with long standing ulcers, commonly accompanied by chronic osteomyelitis and hence need a longer duration of treatment.

Antibiotic Therapy: Empirical antibiotics are commenced according to the severity and the most likely pathogens including Staphylococcus aureus and streptococci. Severe cases are treated using IV antibiotics, the therapy being modified depending on culture findings.

Surgical Debridement: It is important to debride the body areas that have developed necrotizing and infected tissues. In the worst extreme, surgery may be necessary to remove the affected limb to avoid further spreading of the infection.

Wound Care: Appropriate and frequent dressing changes, relieving the pressure of the foot and the possible adjunct use of hyperbaric oxygen therapy for the chronic wound.

Comorbidity Management: In patients with diabetes, glycemic control is an important aspect, as well as the management of peripheral vascular diseases that may require revascularization, and neuropathy to avoid injury.

Advanced Therapies: Application of growth factors, bioengineered skin substitutes and use of negative pressure wound therapy in the management of complex wounds.

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Wound Care Environment: Proper cleansing of the wound and application of proper dressings that will enhance the rate of healing and reduce the chances of the wound getting infected. Special type of dressings can be employed such as hydrocolloids or anti-microbial dressings.

Foot Hygiene and Skin Care: Proper foot protection from infection by washing and moisturizing them besides need to check the feet over at least once a day to check for signs injuries or signs of infections.

Temperature Control: Measuring the temperature of feet to identify tenderness and possible inflammation or infection since issues such as swelling, redness, and heat could be signs of complications.

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Ampicillin/Sulbactam: This product combines the beta-lactamase with ampicillin; it is effective against bacterial cell wall synthesis while the bacteria is actively growing. It provides skin infection, enteric bacteria, and anaerobe coverage and used in place of oral amoxicillin where this is not an option. But it is less effective against hospital infection – causing microorganisms.

Amoxicillin/Clavulanate: Amoxicillin is effective because it interferes with the synthesis of bacterial cell wall, whereas clavulanate blocks enzymes that could degrade certain antibiotics. This combination is safe in patients with macrolide allergy and gives adequate coverage for most infections but does not cover Mycoplasma and Legionella species.

Piperacillin/Tazobactam: It has an antipseudomonal penicillin derivative combined with a beta-lactamase inhibitor. It works by acting on any bacteria cell which is actively synthesizing its wall and for this reason, it is very effective against a wide spectrum of bacterial infections specially those done by Pseudomonas species.

Ticarcillin/Clavulanate: This drug combines and antipseudomonal penicillin with a beta-lactamase inhibitor, making the drug effective in killing the bacterial cell wall during its active growth and formation. It offers great coverage, including many gram-positive and gram-negative organisms and anaerobes pathogens.

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Cephalexin: This antibiotic belongs to first generation cephalosporin that acts bactericidally by inhibiting the synthesis of bacterial cell wall for those bacteria that have rapid rate of multiplication. It can be made resistant through modification of the protein that penicillin binds to. It is particularly useful in treating infections that are caused by alpha-hemolytic streptococci, and staphylococci including the penicillinase-producing variety.

Ceftriaxone: It is a third-generation cephalosporin with activity being wider primarily in the pathogenic gram-negative bacteria. Although it is not very potent against gram-positive bacterias, it demonstrates high activity against resistant ones. Attributed to its bactericidal action includes binding to penicillin binding proteins stabilizing and inhibiting their autolytic enzymes that cause cleavage of peptidoglycan – a critical component of the bacterial cell wall.

Cefoxitin: A second-generation cephalosporin active against certain gram-positive cocci, gram negative rods and anaerobic bacteria. It prevents the formation of bacteria cell wall by formation of complex with penicillin binding proteins and prevents the last step required for the formation of the rigid peptidoglycan layer that would otherwise lead to cell wall synthesis. It can also work against infections that are made by gram-negative bacteria that is resistant to cephalosporin or penicillin.

Cefuroxime: It is another second-generation cephalosporin that retains the gram-positive activity of the first-generation agents and in addition has enterococcal activity and efficacy against organisms such as Proteus mirabilis, Haemophilus influenzae, Escherichia coli, Klebsiella pneumoniae and Moraxella catarrhalis. This is realized by having affinity to those enzymes that are involved in the synthesis of bacteria cell wall referred to as penicillin-binding proteins thus inhibiting the last step of formation of the bacterial cell wall which is broken.

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Meropenem: It is a third-generation crystalline carbapenem antibiotic of the broad-spectrum category which has bactericidal action via impacting, the synthesis of bacterial cell wall. If classified, it is most effective against a broad spectrum of both gram-positive and negative representatives with greater potency against gram negatives while having slightly lower effectiveness against staphylococci and streptococci than imipenem.

Ertapenem: This is a bactericidal antibiotic that mainly functions by preventing the bacterial cell wall synthesis through binding of the penicillin binding proteins. It is relatively insensitive to hydrolysis by penicillinases, cephalosporinases, and extended spectrum beta-lactamases, therefore is highly resistant to beta-lactamase mediated degradation.

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Levofloxacin: It is an antibiotic that is active against a variety of gram-negative bacterial infections including, multidrug resistant bacteria especially in Pseudomonas aeruginosa.

Moxifloxacin: It is a fluoroquinolone antibiotic that inhibits the A subunits of DNA gyrase that affects the bacterial DNA synthesis and transcription thus preventing bacterial development.

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Clindamycin: This is a semisynthetic antibiotic obtained from lincomycin. It works by preventing the release of peptidyl tRNA from the bacterial ribosome affecting RNA directed protein synthesis. It is mainly used in severe skin and soft tissue infections resulting from staphylococci and streptococci excluding enterococci.

Metronidazole: It is an antimicrobial drug that is active against anaerobic bacteria and protozoa and is usually given in combination with other antimicrobials.

Vancomycin: It is a bactericidal antibiotic now mainly used for gram positive organisms and especially enterococci. It is used for septicemia and skin infections however, in patients who cannot use penicillins or cephalosporins or have infections with resistant staphylococci.

Linezolid: It is indicated for bacterial infections of the foot in diabetic patients without evidence of osteomyelitis originating from gram-positive bacteria including MRSA. It prevents the formation of the 70S initiation complex that validates bacterial translation. Beneficial against enterococci and staphylococci but bactericidal in many cases of streptococci. Contraindicated in patients taking serotonergic psychiatric drugs, as this can cause serotonin syndrome.

Tigecycline: Used to treat a range of bacterial infections, it works in a manner that it interferes with protein synthesis within bacterial cells by attaching itself to the 30S ribosomal protein. It is used in complicated skin infections and is active against E. coli, Enterococcus faecalis (VSE), both MSSA and MRSA and other streptococci and anaerobic organisms.

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Daptomycin: It works on bacterial membranes and thus causes rapid depolarization of the membrane potential. This process inactivates proteins required for synthesis of new proteins, DNA and RNA and leads to dead cells. It is used to treat moderate to severe skin and skin structure infections.

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Debridement: Debridement is defined as the process of surgical cleaning in which necrotic tissue, foreign debris, as well as infected tissue are surgically removed with an aim of enhancing the healing process and decrease bacterial density.

Types:

Sharp Debridement: Carried out with scalpels or scissors, it is the best way of excision of necrotic tissue.

Mechanical Debridement: It involves application of wet to dry dressings or irrigation.

Autolytic Debridement: Applying moisture-retentive dressings so that the dead tissue digests itself.

Enzymatic Debridement: Implies the application of topical agents like collagenase to dissolve the necrotic tissue.

Surgical Intervention

Drainage of Abscesses: Any abscesses can be opened for surgical I & D to decrease pressure and obtain appropriate amount of unobstructed flow.

Amputation: Surgical removal of infected toes or parts of the foot may be required in cases of extensive tissue loss or osteomyelitis to avoid a systemic infection as well as other complications.

Revascularization Procedures

Angioplasty or Bypass Surgery: In patients where arterial disease is an important component in the development of foot ulcers and infections, then correction of the arterial supply through percutaneous angioplasty or even bypass surgery can help facilitate healing.

Osteomyelitis Management

Bone Debridement: If osteomyelitis is found, surgery may be done to remove infected bone because it may be the source of the infection.

Bone Stabilization: For major soft-tissue injuries leading to major structural instability of the foot, surgical intervention is sometimes required to temporarily support the structure while the tissue heals.

Negative Pressure Wound Therapy (NPWT): Actually, this technique employs vacuum dressing as a method helpful in wound healing because it reduces edema, enhances blood circulation and brings wound edges close.

Skin Grafting: In cases of extensive ulcers or defects that do not heal with watch waiting approach, skin grafting may be used to provide a dress for the wound with the intention of healing.

Hyperbaric Oxygen Therapy (HBOT): In some circumstances, the given therapy serves to improve oxygen supply with hypoxic tissues preventing infection and aiding healing.

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Management of diabetic foot infections is a phased approach. Initially, after the assessment and diagnosis, it is essential to eliminate infection which involves antibiotic therapy and debridement of necrotic material. Then, the management of comorbidities such as controlling blood glucose levels which is essential in promoting the wound healing. The next step would be to drain abscesses either surgically or through aspiration. Foot amputations can be carried out if the infection is severe and causes tissue damage. The subsequent stages of foot management are multidisciplinary rehabilitation which focuses mainly on the management, foot care to prevent infections of foot ulcers.