Diabetic Foot Infection
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Diabetic foot infection is any infection of the foot in a diabetic person. The most frequent cause of hospitalization for diabetic patients is due to foot infections. Symptoms may include
pus Pus is an exudate, typically white-yellow, yellow, or yellow-brown, formed at the site of inflammation during bacterial or fungal infection. An accumulation of pus in an enclosed tissue space is known as an abscess, whereas a visible collection ...
from a wound, redness, swelling, pain, warmth,
tachycardia Tachycardia, also called tachyarrhythmia, is a heart rate that exceeds the normal resting rate. In general, a resting heart rate over 100 beats per minute is accepted as tachycardia in adults. Heart rates above the resting rate may be normal ( ...
, or tachypnea. Complications can include infection of the bone,
tissue death Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dige ...
,
amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on ind ...
, or
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is foll ...
. They are common and occur equally frequently in males and females. Older people are more commonly affected. They most often form following a
diabetic foot ulcer Diabetic foot ulcer is a major complication of diabetes mellitus, and probably the major component of the diabetic foot. Wound healing is an innate mechanism of action that works reliably most of the time. A key feature of wound healing is stepw ...
, though not all foot ulcers become infected. Diabetic foot ulcers can be caused by
vascular disease Vascular disease is a class of diseases of the blood vessels – the arteries and veins of the circulatory system of the body. Vascular disease is a subgroup of cardiovascular disease. Disorders in this vast network of blood vessels can cause a ...
or
neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
and its prevalence occurs in approximately 25% of diabetics throughout their lifetime. Some risk factors for developing diabetic foot infections include history of repeated foot ulcers, foot ulcers lasting for longer than 30 days, poor control over
blood glucose Glycaemia, also known as blood sugar level, blood sugar concentration, or blood glucose level is the measure of glucose concentrated in the blood of humans or other animals. Approximately 4 grams of glucose, a simple sugar, is present in the bl ...
levels, peripheral neuropathy, renal impairment,
peripheral artery disease Peripheral artery disease (PAD) is an abnormal narrowing of arteries other than those that supply the heart or brain. When narrowing occurs in the heart, it is called coronary artery disease, and in the brain, it is called cerebrovascular diseas ...
, injury or trauma to foot, walking barefoot frequently, and history of amputation in lower limbs. Most diabetic foot infections are polymicrobial (contain multiple infective organisms), and bacteria that are commonly involved include
staphylococcus ''Staphylococcus'' is a genus of Gram-positive bacteria in the family Staphylococcaceae from the order Bacillales. Under the microscope, they appear spherical ( cocci), and form in grape-like clusters. ''Staphylococcus'' species are facultat ...
, including
methicillin resistant staphylococcus aureus Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
(MRSA),
streptococci ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci ...
,
pseudomonas ''Pseudomonas'' is a genus of Gram-negative, Gammaproteobacteria, belonging to the family Pseudomonadaceae and containing 191 described species. The members of the genus demonstrate a great deal of metabolic diversity and consequently are able ...
, and
gram-negative bacteria Gram-negative bacteria are bacteria that do not retain the crystal violet stain used in the Gram staining method of bacterial differentiation. They are characterized by their cell envelopes, which are composed of a thin peptidoglycan cell wa ...
. Previously, MRSA infections were usually acquired from hospital settings, however, recently MRSA infections acquired from the community are becoming more prevalent and are linked to poor treatment outcomes for diabetic patients. Some risk factors for developing MRSA infections include use of antibiotics that cover a broad spectrum of pathogens for a long duration of time, prolonged hospital stay, or certain surgical procedures. The underlying mechanism of diabetic foot infections often involves poor blood flow and
peripheral neuropathy Peripheral neuropathy, often shortened to neuropathy, is a general term describing disease affecting the peripheral nerves, meaning nerves beyond the brain and spinal cord. Damage to peripheral nerves may impair sensation, movement, gland, or or ...
. Diagnosis is based on symptoms and may be supported by deep
tissue culture Tissue culture is the growth of tissues or cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, su ...
. Treatment involves proper
wound care The history of wound care spans from prehistory to modern medicine. Wounds naturally heal by themselves, but hunter-gatherers would have noticed several factors and certain herbal remedies would speed up or assist the process, especially if it wa ...
and
antibiotics An antibiotic is a type of antimicrobial substance active against bacteria. It is the most important type of antibacterial agent for fighting bacterial infections, and antibiotic medications are widely used in the treatment and prevention ...
. ''Pseudomonas aeruginosa'' empiric therapy is not warranted unless the patient had a previous infection with a culture identifying the organism, or if the patient has risk factors for it such as frequent use of wet dressings or living in hot climates. MRSA empiric therapy is also not warranted unless the patient has a critical infection such as
sepsis Sepsis, formerly known as septicemia (septicaemia in British English) or blood poisoning, is a life-threatening condition that arises when the body's response to infection causes injury to its own tissues and organs. This initial stage is foll ...
, if the rate of MRSA infections are particularly high in a local area, or if the patient had a previous MRSA infection. The duration of antibiotics depends on the severity of infection, ranging anywhere from 1–12 weeks. Treatment of mild-moderate infections should last 1–2 weeks and typically requires oral antibiotics that cover staphylococci and
streptococci ''Streptococcus'' is a genus of gram-positive ' (plural ) or spherical bacteria that belongs to the family Streptococcaceae, within the order Lactobacillales (lactic acid bacteria), in the phylum Bacillota. Cell division in streptococci ...
. Severe infections typically require IV antibiotics that cover more pathogens, such as gram positive organisms, gram negative organisms, and obligate anaerobes to allow for better treatment outcomes. Total antibiotic treatment of severe infections should be approximately 2–3 weeks or more, depending on how extensive the infection is. Prevention includes wearing appropriate shoes, regular foot examinations, and control of risk factors.


Mechanism

Neuropathy, peripheral artery disease, and trauma contribute individually and in combination to the pathophysiology of diabetic foot infections.


Neuropathy

Diabetes causes a symmetric
polyneuropathy Polyneuropathy (poly- + neuro- + -pathy) is damage or disease affecting peripheral nerves (peripheral neuropathy) in roughly the same areas on both sides of the body, featuring weakness, numbness, and burning pain. It usually begins in the hands ...
that may affect motor and sensory neurons. Intrinsic atrophy of foot and ankle muscles leads to anatomic changes of the foot arch, most commonly depressing the
metatarsal The metatarsal bones, or metatarsus, are a group of five long bones in the foot, located between the tarsal bones of the hind- and mid-foot and the phalanges of the toes. Lacking individual names, the metatarsal bones are numbered from the med ...
heads and creating high pressure zones. Neuropathy is present in approximately 60% of patients who develop foot ulcers and are also diabetic. Neuropathy can lead to a loss of sensation for diabetics in their feet, therefore when there is any trauma/injury or foot ulcer present in these patients it can take awhile for patients to notice; this can lead to an infection developing and worsening while the patient is unaware due to the loss of sensation and lack of pain. In combination with decreased sensation in the lower extremities, repetitive trauma from walking can lead to ulceration. Poor foot care, including lack of moisturizing and frequent self-examination of the feet can exacerbate this.


Peripheral artery disease

Metabolic changes in diabetes, including
hyperglycemia Hyperglycemia is a condition in which an excessive amount of glucose circulates in the blood plasma. This is generally a blood sugar level higher than 11.1  mmol/L (200  mg/dL), but symptoms may not start to become noticeable until even ...
, lead to increased likelihood of -
hyperlipidemia Hyperlipidemia is abnormally elevated levels of any or all lipids (fats, cholesterol, or triglycerides) or lipoproteins in the blood. citing: and The term ''hyperlipidemia'' refers to the laboratory finding itself and is also used as an umbr ...
and developing
atherosclerosis Atherosclerosis is a pattern of the disease arteriosclerosis in which the wall of the artery develops abnormalities, called lesions. These lesions may lead to narrowing due to the buildup of atheromatous plaque. At onset there are usually ...
. In diabetes, this atherosclerosis is preferentially distributed to the posterior and anterior tibial arteries, decreasing
perfusion Perfusion is the passage of fluid through the circulatory system or lymphatic system to an organ or a tissue, usually referring to the delivery of blood to a capillary bed in tissue. Perfusion is measured as the rate at which blood is deliv ...
to the lower extremities. This may lead to loss of skin integrity, ischemic ulcers, and
gangrene Gangrene is a type of tissue death caused by a lack of blood supply. Symptoms may include a change in skin color to red or black, numbness, swelling, pain, skin breakdown, and coolness. The feet and hands are most commonly affected. If the gan ...
. Infection may vary in the depth of tissue to which it extends. Foot infections range from the most superficial,
cellulitis Cellulitis is usually a bacterial infection involving the inner layers of the skin. It specifically affects the dermis and subcutaneous fat. Signs and symptoms include an area of redness which increases in size over a few days. The borders of ...
, to deeper soft tissue
necrotizing fasciitis Necrotizing fasciitis (NF), also known as flesh-eating disease, is a bacterial infection that results in the death of parts of the body's soft tissue. It is a severe disease of sudden onset that spreads rapidly. Symptoms usually include red or p ...
, which may necessitate limb amputations or become life-threatening. Infections may also extend to bone, termed
osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
. Infections are commonly polymicrobial and involve antibiotic-resistant strains of organisms e.g.
MRSA Methicillin-resistant ''Staphylococcus aureus'' (MRSA) is a group of Gram-positive bacteria that are genetically distinct from other strains of ''Staphylococcus aureus''. MRSA is responsible for several difficult-to-treat infections in humans. ...
.


Diagnosis

Initial diagnosis of diabetic foot infections is made primarily via thorough history and physical to include visual inspection of the feet, evaluation of any wounds, distal pulses, and neurologic function.


History and physical

History should be taken for known recent foot trauma, and the lower extremities should be inspected for signs of recent trauma, including redness,
induration A skin condition, also known as cutaneous condition, is any medical condition that affects the integumentary system—the organ system that encloses the body and includes skin, nails, and related muscle and glands. The major function of thi ...
,
edema Edema, also spelled oedema, and also known as fluid retention, dropsy, hydropsy and swelling, is the build-up of fluid in the body's tissue. Most commonly, the legs or arms are affected. Symptoms may include skin which feels tight, the area ma ...
, visible ulceration with exudate or pus, or bony deformity. Ulcers do occur in the absence of pathological infection. Diagnosis of an infected wound is classically made with ≥2 signs of inflammation or purulence. Peripheral pulses should also be evaluated (posterior tibial and dorsal pedis), and if not palpable, should be further evaluated using ultrasound. In patients with non-palpable pulses, evaluation of PAD with an ankle-brachial index should also be performed. Ulceration or deeper wounds should be probed to identify the depth of penetration and determine involvement of bone, which would indicate osteomyelitis. Neurologic testing includes testing peripheral sensation to vibratory stimuli, temperature, pain, along with deep tendon reflexes.


Imaging

Imaging may also be used for further evaluation. Plain x-ray, the most common initial imaging study, may show fractures,
osteomyelitis Osteomyelitis (OM) is an infection of bone. Symptoms may include pain in a specific bone with overlying redness, fever, and weakness. The long bones of the arms and legs are most commonly involved in children e.g. the femur and humerus, while the ...
, gas collection from gas-producing infective organisms, calcification of blood vessels, or foreign bodies. Magnetic resonance imaging (MRI) is useful to determine the depth of soft tissue infection and evaluate for presence of osteomyelitis, especially in patients which do not respond to initial antibiotic therapy. Finally, patency of the lower extremity
vasculature The blood circulatory system is a system of organs that includes the heart, blood vessels, and blood which is circulated throughout the entire body of a human or other vertebrate. It includes the cardiovascular system, or vascular system, tha ...
may be evaluated by magnetic resonance
angiography Angiography or arteriography is a medical imaging technique used to visualize the inside, or lumen, of blood vessels and organs of the body, with particular interest in the arteries, veins, and the heart chambers. Modern angiography is perfo ...
or ultrasonography If a patient is experiencing a diabetic foot infection for the first time, a plain radiograph should be conducted to look for any bone abnormalities. MRI is more sensitive and specific than a radiograph, and is typically done if osteomyelitis is suspected and the diagnosis is unclear from the radiograph, or if an abscess is suspected in soft tissue.


Management

Acute management of diabetic foot infections generally includess antibiotic therapy, pressure offloading, re-vascularization, if appropriate, and
debridement Debridement is the medical removal of dead, damaged, or infected tissue to improve the healing potential of the remaining healthy tissue. Removal may be surgical, mechanical, chemical, autolytic (self-digestion), and by maggot therapy. ...
of infected tissues (or amputation if necessary). Hospitalization is more likely needed when lower extremity pulses are absent or when infection penetrates to the level of the fascia or more deeply. Infections with skin gangrene may reflect deep space infection, abscess, and tissue
necrosis Necrosis () is a form of cell injury which results in the premature death of cells in living tissue by autolysis. Necrosis is caused by factors external to the cell or tissue, such as infection, or trauma which result in the unregulated dig ...
. When debridement is necessary, wounds are left open so that serial debridements may be performed over the course of the wound’s healing. Antibiotic choice should be guided by deep
tissue culture Tissue culture is the growth of tissues or cells in an artificial medium separate from the parent organism. This technique is also called micropropagation. This is typically facilitated via use of a liquid, semi-solid, or solid growth medium, su ...
, severity of the infection, presence or absence of osteomyelitis, prior antibiotic treatment, and previous or current MRSA infection. Wounds without confirmed infection should not be treated with antibiotics, nor should be sent for culture. Cultures are not necessarily warranted if a patient has a mild infection and they have not been on any antibiotics recently. Before starting empiric therapy, cultures should be obtained and once results come back from the lab, an appropriate antibiotic with a narrower spectrum should be chosen. Length of treatment depends primarily on severity of infection; skin and superficial soft tissue infections may require treatment for 1–2 weeks while deeper infections (including osteomyelitis) may require 6–12 weeks, including those who undergo surgery.{{Cite journal , last1=Barwell , first1=Nicholas D. , last2=Devers , first2=Marion C. , last3=Kennon , first3=Brian , last4=Hopkinson , first4=Helen E. , last5=McDougall , first5=Claire , last6=Young , first6=Matthew J. , last7=Robertson , first7=Hannah M. A. , last8=Stang , first8=Duncan , last9=Dancer , first9=Stephanie J. , last10=Seaton , first10=Andrew , last11=Leese , first11=Graham P. , date=2017 , title=Diabetic foot infection: Antibiotic therapy and good practice recommendations , url=https://onlinelibrary.wiley.com/doi/abs/10.1111/ijcp.13006 , journal=International Journal of Clinical Practice , language=en , volume=71 , issue=10 , pages=e13006 , doi=10.1111/ijcp.13006 , pmid=28892282 , s2cid=40277094 , issn=1742-1241


Prevention

One crucial aspect for prevention of diabetic foot infections is educating patients of what to monitor for and when to follow up with a healthcare professional. Patients should be regularly checking their feet daily, if they are not able to view the bottom of their feet they can use a mirror to aid them. Prevention of diabetic foot infections include regular foot examinations by a healthcare professional as well as maintenance of cardiovascular
co-morbidities In medicine, comorbidity - from Latin morbus ("sickness"), co ("together"), -ity (as if - several sicknesses together) - is the presence of one or more additional conditions often co-occurring (that is, concomitant or concurrent) with a primar ...
and risk factors. This maintenance includes proper footwear, regulating blood glucose and hypertension, and limiting cardiovascular risk factors, such as smoking. Patients should avoid exposing their feet to hot water or harsh chemicals, as well should avoid walking barefoot to prevent development of diabetic foot infections. Patients should also be educated about the importance of regularly trimming their toenails and ensuring they are kept short to avoid an infection from developing. All patients with diabetes should be examined at least yearly if no additional risk factors, but more frequently if present. In those with a prior ulcer or
amputation Amputation is the removal of a limb by trauma, medical illness, or surgery. As a surgical measure, it is used to control pain or a disease process in the affected limb, such as malignancy or gangrene. In some cases, it is carried out on ind ...
, examinations are needed every 1–2 months.


References

Diseases and disorders Diabetes