diabetic related infection and management

DIABETIC RELATED INFECTION AND MANAGEMENT

Complications of Diabetes Mellitus

Acute Chronic

1. Diabetic Ketoacidosis

2. Hyperosmolar Nonketotic Coma

3. Hypoglycemia

1. Microangiopathy-Stroke-IHD-Peripheral Vascular Disease

2. Macroangiopathy-Diabetic retinopathy-Diabetic nephropathy-Diabetic neuropathy

3. Diabetic foot

Pathogenesis of Chronic Complication

1. Formation of Advanced Glycation End products(AGEs)

2. Activation of Protein Kinase C (PKC)

3. Intracellular hyperglycemia with disturbance of polyol pathway

Formation of Advanced Glycation End Products (AGEs)

Intracellular glucose-derived dicarbonyl precursors

+ (Non enzymatic reaction)

Amino group (intracellular & extracellular protein)

AGEs

Effects of glycosylation

Extracellular matrix protein

Circulating plasma protein

Cross-links between polypeptide(Eg.

Collagen)

Trap non-glycosylated plasma and interstitial protein

Trapping LDL at vessel wall accelerates

atherogenesis

Binds to AGE receptors on endothelial cells, mesangial cells &

macrophages

•Release cytokines & GF

•Increase vascular permeability

•Induce procoagulant activity

•Enhance ECM synthesis

Trapping albumin at BM thickens BM in diabetic

glomerulopathy

Activation of Protein Kinase CIntracellular hyperglycaemia

Stimulates de novo synthesis for diacylglycerol (DAG)

Activates PKC

Downstream effects:•Production of vascular endothelial growth factor •Increased vasoconstriction•increased deposition of extracellular matrix and basement membrane material•Production of plasminogen activator inhibitor •Production of proinflammatory cytokines

Polyol pathway

Glucose Sorbitol Fructose

NADPH + HNADPH + H++ NADP+

NAD+ NADH + H+

Aldosereductase

Polyoldehydrogenase

Disturbance in polyol pathwayHyperglycemia

increase IC glucose

(eg: nerves, lens, kidney, blood vessels)

metabolize by aldose reductase

sorbitol (polyol)

Fructose

Accumulated sorbitol & fructoseAccumulated sorbitol & fructose

Increase IC osmolarityIncrease IC osmolarity

Influx of waterInflux of water

Osmotic cell injury Osmotic cell injury

NADPH used up during polyol pathway

Decreased GSH (Reduced glutathione)

Cells susceptible to oxidative stress

Oxidative cell injury

Risk factor

• Diabetic foot ulcer is a combination of peripheral vascular disease (PVD), peripheral neuropathy (PNP), immunocompromised and infection.

• Other factors have been identified such as repetitive stress and pressure on insensitive feet, poor glycaemic control and others

Peripheral neuropathy 1. Chronic sensorimotor neuropathy• Sensory component - onset is insidious and

cause reduce or loss of sensation to vibration, painful and thermal stimuli.

• Severe case, proprioception may be affected and patient develop sensory ataxia.

• Motor component – atrophy of small intrinsic muscle of foot and cause unopposed pulling of extensor and flexor tendon resulting in clawing of toe and prominence of metatarsal head

• This lead to abnormal pressure point, which in an insensitive foot ultimately predispose to diabetic foot ulcer

Peripheral neuropathy

2. Autonomic neuropathy• Decrease sweat production dry foot

crack and fissure formation serve as nidus for infection and ulceration

• Increase arteriovenous shunting and raised venous pressure

• Impaired cutenous hyperaemic respond to injury

• Impaired vasoregulatory respond to changes in temperature.

Peripheral vascular disease

• DM increase risk of atheroslerosis• Reduce lower limb transcutenous oxygen tension and

reduce large vessel perfusion • This will cause delayed wound healing and development

of gangrene.• Diabetic patient also have an increase risk of

coagulability and thrombosis role in impairment of tissue perfusion and difficulty in delivering antibiotic

• Lazy lymphocyte syndrome – leukocyte function is impaired in uncontrolled diabetic

• Abnormality in migration, phagocytosis, intracelullar killing and chemotaxis and this is likely to interfere with healing process of diabetic foot.

Biomechanical factor

• Non-enzymatic glycosylation of collagen results in stiffening of connective tissue surrounding the joints leading to limited joint mobility.

• This causes increased plantar pressure during normal gait.

• Callus is known to contribute to high plantar foot pressure acting as an extrinsic source of stress and is highly predictive of subsequent ulceration.

Infection

• DM impaired tissue perfusion and lazy leukocyte syndrome cause delayed wound healing.

• Gram positive cocci – Stap. aureus, Strep. spp, Corynebacterium spp.

• Gram negative rod – E. coli, proteus species

Somatic neuropathy

•Reduce pain

•Diminished proprioception

•Clawing of toes

Autonomic neuropathy

•Absent sweating

•Dry skin fissure

•Altered blood flow regulation

•Distended foot veins

•Charcot neuroarthropathy

Peripheral vascular disease

•Claudication: rest pain

•Cold extremities

•Reduced foot pulses

Increase foot pressure

Callus formation Foot ischaemia

Foot ulceration

Gangrene

Infection

Amputation

Connective tissue change

•Limited joint mobility

•Orthopaedic disorder

SOFT TISSUE INFECTION

Factor that affect host respond

Systemic factor• Malnutrition• Renal and hepatic failure• Diabetes mellitus• Cancer • Immunosuppressive

therapy• Chronic hypoxia• Immune deficiency• Extremes of age• Alcohol abuse• Active cigarette abuse

Local factor• Major vessel compromise• Chronic lymphoedema• Arteritis• Extensive scarring• Radiation fibrosis• Small vessel disease• Venous stasis• Insensate region

Folliculitis• Infection of hair follicles

• Risk factor

- exfoliation of skin

- damage hair follicle (shaving, use of loofan sponge)

• Stap aureus or Stap epidermidis

Furuncle

• Skin disease caused by inflammation of hair follicle, thus resulting in the localized accumulation of pus and dead tissue.

• Common bacteria infection:

* stap aureus

* stap epidermidis

Carbuncle

• Collection of multiple furuncle characterize by red, hot, painful nodule that often drains pus through multiple openings of the skin.

• Usually extends into the deeper layers of the skin -- the subcutaneous fat.

• tend to occur in areas with thicker skin like the nape of the neck, the back, or the thighs.

Cellulitis • Acute spreading inflammation involving the

epidermis, dermis and subcutenous fat• Often occurs where the skin has previously been

broken: cracks in the skin, cuts, blisters, burns, insect bites, surgical wounds, or sites of IV cathether insertion

• Can be caused by normal skin flora or by exogenous bacteria

• Crepitant anaerobic cellulitis appears as a necrotic soft tissue infection with abundant connective tissue gas. Characterize by gradual onset, absence of muscle involvement, lack of marked systemic toxicity.

Causative Agents

Commonly caused by group A streptococci especially Streptococcus pyogenes

Occasionally streptococci from other Lancefield groups such as B, C and G can also cause cellulitis

Majority of celulitis (facial cellulitis) in childhood are caused by Staphylocuccus aureus, less commonly by Haemophilus influenzae type b, but they rarely cause cellulitis in adult.

Necrotizing Fasciitis• Is an infection of subcutaneous tissue and fascia

characterized by progressive necrosis.• Rare infection with high mortality (30 – 40 %)• Clinical menifestation include necrosis of the superficial and

often deep fascia.• Types of necrotizing fasciitis

# type 1-polymicrobial form (Mixed infection of anaerobic and aerobic bacteria)# type 2-monomicrobial form

• Aerobic organism especially Strep. pyogenes, Stap. aureus and members of E. coli, Enterobacteriaceae

• Anaerobes organism is Peptostreptococcus, Bacteroides, Fusobacterium

Clinical features• Initially begins as cellulitis which advances slowly -

redness, oedema, pain, very tender and warm • Over the next 2- 4 days, skin changing from red to purple

to pathognomonic gray- blue with ill- defined patches• Haamorrhagic bullae may develop• Necrosis of superficial fascia and ‘dishwater pus’

discharge• Meanwhile, systemic toxicity develops- high grade fever

with chill and malaise, tarchycardia,generalised toxicity septic shock

• *As infection spreading along the fascia, intensity of pain is in excess given external skin lesion.

• * woody hard feel of the subcutaneous tissue while in erysipelas or cellulits is yielding (give way to pressure)

Diagnose NF

• Failure to respond to initial antibiotic therapy

• Little improvement even on therapy

• Woody- hard feel of subcutaneous tissue extending beyond the skin involvement

• Systemic toxicity often with altered mental status

NF at presentation rapid progression seen after 24hours

Gas gangrene• Terrifying condition is produce by Clostridial infection

primarily of muscle tissue.• Clostridial species:

*clostridium perfringens 90%*clostridium novyi 4%*clostridium septicum 2%*clostridium histolyticum

• Gram positive bacilli, anaerobic organism that can survive and multiply only in tissue with low oxygen tension eg. dirty wound with dead muscle, area of major trauma or surgery or as complication of thermal burns

• Immunocompromised, diabetic, or malignant disease are at greater risk

• Toxins produce by the organism destroy the cell wall and rapidly lead to tissue necrosis.

Gas gangrene

• Clinical features appear with in 24hours of the injury

• Pain and swelling around the wound• Crepitus ( gas in tissue)• Brownish discharge, exudate describe as having

a “sweet mousy odour”• Little or no pyrexia• Pulse rate increase• Patient becomes toxaemic

Diagnose GG• Diagnosed mainly on a clinical basis• Step 1 - Expect the onset of gas gangrene to be sudden and

dramatic. There will be a pale to brownish red inflammation at the site of the infection with very painful swelling. Gas may be felt under the skin when the swollen area is pressed and the infection can expand quickly enough to be seen. Blisters may form with brown-red fluid and have a bad-smelling discharge.

• Step 2 - Use the extreme pain of the infection to distinguish gas gangrene from cellitus. This is due to the muscles not getting enough oxygen.

• Step 3 - Observe systemic symptoms of gas gangrene such as moderate to high fever and sweating. The skin may be initially pale with cold extremities, but then become yellow as blood cells break down. The patient can develop hypotension, rapid heart rate, kidney failure, coma and death if left untreated.

• Step 4 - Perform routine laboratory tests to indicate gas gangrene. Conduct a gram stain of infected fluid to see gram-positive bacteria. A CT scan, MRI or X-ray may show gas in the tissue.

• Step 5 - Confirm the diagnosis by growing a culture of cloistridium from infected fluid or tissue.

• Plain X-ray often shows gas in the subcutaneous tissue and fascial plains

MANAGEMENT

PREVENTION IS BATTER THAN CURE

Management of diabetic foot ulcer

1. Regular inspection and examination

2. Investigation

3. Treatment

Examination-inspection

• ischemic or neuropathy ulcer

• infected ulcer or not

• Discharge

• Sign of osteomylitis

• Sign of charcot joint

Wagner Ulcer Classification System

• Grade 0 - No open lesions; at risk• Grade 1 - Superficial diabetic ulcer (partial or full

thickness) • Grade 2 - Ulcer extension to ligament, tendon, joint

capsule, or deep fascia without abscess or osteomyelitis• Grade 3 - Deep ulcer with abscess, osteomyelitis, or joint

sepsis• Grade 4 - Gangrene localized to portion of forefoot or

heel • Grade 5 - Extensive gangrenous involvement of the

entire foot

Ischaemia VS Neuropathy

Ischaemia Neuropathy

Symptoms Claudication

Rest pain

Usually painless

Or painful neuropathy

Inspection Dependent rubor

Trophic changes

High arch + clawing of toes

Present or No trophic changes

Palpation Cold

Pulseless

Warm

Bounding pulses

Ulceration Painful

Heels and toes

Painless

Plantar

Ischemic foot ulcer

Dorsum of 2nd toe shows ischaemic lesion.Whitish color on the tipd/t ischaemia

Neuropathic foot ulcer

Ulcer on the 1st metatarsal head.Health granulation tissue on its bed.Callus formation on its surrounding ulcer lesion.

Mixed etiology (Neuro-ischemic) ulcer

Gangrene

Death of tissue usually in considerable massGenerally d/t loss of vascular supply& followed by bacterial infection

Investigation

1. Random blood sugar

2. FBC

3. Deep swab from ulcer base for culture and sensitivity

4. Plain radiograph of foot and ankle

6. Neurological investigation Two-point discrimination monofilament test vibration perception are used toassess

peripheral sensory neuropathy

Investigation

6. Vascular investigation:- Ankle- brachial systolic index

- >1.0 normal- <0.9 some degree of arterial obstruction- <0.3 suggests imminent necrosis

Toe systolic pressure- <40mmHg

Transcutenous PO2 level- <30mmHg

Doppler ultrasound

Treatment• Primary goal obtain wound closure

prevent limb loss

prevent ulceration and recurrence

maintain quality of life and

prevent further complication• Management of DFU is largely determined by

severity, vascularity and present of infection• Proper treatment of diabetic foot ulcers can lower

the incidence of lower limb amputations

Treatment for DFU

• Principle of treatment-Debridement of necrotic tissue-Wound care-Reduction of plantar pressure (off-loading) (eg. total non-weight bearing,total contact cast, foot cast or boots)-Treatment of infection-Vascular management of ischaemia (vascular reconstruction surgery )-Medical management of co morbidities-Surgical management to reduce or remove bony prominences and improve soft tissue cover-Reduce risk of recurrence

Debridement

• removal of all non-viable tissues and slough from the ulcer.

• Diabetic foot ulcers should be frequently and thoroughly debrided of necrotic tissues to enhance healing process

Wound care

• Moist wound environment bandaged to protect it from trauma and local contamination

• To facilitate the healing process

• Type of dressing depend on size, depth, location and wound surface

• Normal saline are use for standard wound care

Surgical Management of DFU

• Chronic foot ulcers are usually associated with areas of increased peak pressure where off loading and wound care techniques are not effective

• Then it treated surgically to reduce high-pressure areas or to redistribute pressure evenly so as to affect ulcer healing.

• All infected bones and tissues are to be removed and amputation done for gangrenous parts until viable bones and tissues are attained to allow optimum function of the remaining foot.

• The wounds are packed with antiseptic dressing and periodically assessed during wound care.

• use of local flaps, split skin grafts or full thickness grafts may be required (act as secondary wound healing)

Surgical treatment • Surgery on infected site includes debridement of wounds,

incision & drainage of abscesses,necrotising fascitis and amputations of gangrenous tissues

• Repeated procedures may be necessary to control infection • Indications for amputation: ( 3D – dead, dangerous,

damned nuisance)Minor amputations:* As part of open debridement* Chronic neuropathic ulcer – if too much tissue loss to save digit* Ischaemia – after infection is controlled and limb is revascularisedMajor amputations:* Extensive tissue loss* Unreconstructable ischaemia* Failed revascularisation* Charcot’s of ankle with instability

Treatment for DFU + infection

Principle of treatment • Surgical treatment• Wound care• Antibiotic treatment• Hyperglycemia control• Correct electrolytes• Optimize comorbidities• Frequent reassessment of response to treatment• If infection subsides but ulcer persists, follow

principles of diabetic ulcer treatment• Prevention

Antibiotic 1) Empirical antibiotics

I. Benzylpenicillin or ampicillin – Streptococcus sp.II. Oxacillin, nafcillin or 1st generation cephalosporin (eg. cefazolin) –

Staphylococcus sp.III. Quinolone + aminoglycoside (gentamycin) – Pseudomonas sp.IV. Methicillin-resistant Staphylococcus aureus – vancomycin or cotri-

moxazole

2) Clostridial species are sensitive to a combination of penicillin G and clindamycin

3) Duration of antibiotic treatment * 1-2 weeks course for mild to moderate infections * more than 2 weeks for more serious infections * 6 - 8weeks for osteomyelitis * If all infected bone is removed,a shorter course (1-2 weeks) of antibiotics, as for soft tissue infection, maybe adequate

Depth Classification

Definition Treatment

0At-risk foot, no ulceration

Patient education, accommodative footwear, regular clinical examination

1Superficial ulceration, not infected

Offloading with total contact cast (TCC), walking brace, or special footwear

2Deep ulceration exposing tendons or joints

Surgical debridement, wound care, offloading, culture-specific antibiotics

3Extensive ulceration or abscess

Debridement or partial amputation, offloading, culture-specific antibiotics

Ischemia Classification

A Not ischemic

BIschemia without gangrene

Noninvasive vascular testing, vascular consultation if symptomatic

CPartial (forefoot) gangrene

Vascular consultation

D Complete foot gangreneMajor extremity amputation, vascular consultation

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