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INFECTIONS AND DIABETES DR.AWADH AL-ANAZI Asst.Professor Consultant, infeciouse diseases Department of medicine King Khaled Hospital College of medicine DIABETES & INFECTIONS • Diabetics subject to same infections as non-diabetics • Diabetic patients more susceptible to infection • Infections in Diabetics more severe & difficult to treat • Certain infections in Diabetics require more Hospitalisation days than other Diabetic complications • In U.S.A. > 60% Major Amputations as complication of D.M. • Thus importance of Diabetic Foot to ALL H.C.W. • Few Infectious conditions exceptionally much more prevalent in Diabetics: * Malignant otitis exterma * Mucormycosis • Other infections appear more common in Diabetics: * Pyelonephritis * Emphysematous cholangitis • Infections indirectly due to Diabetic complications * cystitis & upper U.T.I. In patients with neurogenic bladder * various forms of gangrene of cellulitis in patients with L.L. vascular disease and Diab neuropathy. PATHOPHYSIOLOGY 1. Systemic Factors • Diabetic more susceptible to infection --- not definite • But once infected, more severe & difficult to treat * Diabetic immune defenses have functional defects • Decreased lymphocytes response • Decreased lymphocytes glucose metabolism • Defective PMN : Phagocytosis intracellular killing • Chemotaxis & adherence • All diabetic patients with acidosis have defective phagocytes & cell killing functions. • Poor glycemic control assoc. with increased infections incidence in diabetics. • Other Factors contributing to infection in Diab. * Blood hypercoagulability * RBC & Plts. Changes * connective tissue changes due to glycosylation of glycogen. 2. ISCHEMIA • Most Diab. Patients elderly, obese, with long Hx DM-2. •Smoking more in diabetics with diabetic foot. •Vascular Dis: HTN, Hyperlipidemia, CAD, CVA, more severe in patients with D.F. 3. PERIPHERAL NEUROPATHY • Loss of protective pain sensations • Repeated injuries to insensitive limb • 80% D.F. patients have peripheral neuropathy • Charcot’s joints & diabetic osteopathy • Neuropathic ulcerations • Other sources: superficial fungal infections, improper nail trimming MICROBIOLOGY 1. Mild non-limb-threatening infection * 50% monomicrobial * S.aureus more than 50% * aerobic streptoccoi * GNB * anaerobes 2. Severe-Limb-Threatening infections * usually polymicrobial * some studies quoted 5 species per pts. * Asoc. With advanced vascular disease * Deep tissue culture, avoiding surface contamination, usu, Yield mixed aerobe and anaerobe cultures Limb-threatening Infection: Aerobes: a) S.Aureus & CNS: • Most common aerobic isolates. • Found in two third of patients with single organism isolated. b)Streptococci and enterococci : 20 % • CNS, enterococci, corynebacterium: • These may be contaminant unless * isolated in pure cultures * OR pts. Not responding to Abx Not directed to them c) Enterobacteriaceae : 24 – 27% * proteus, Enterobacter * E.Coli, pseudomonas * klebsiella, Acinetobacter GNB * Morganella morganii •Anaerobes: • 40 – 80% pts. With severe or advanced disease • USU Yielding 4 organism or more on culture •Growth density higher than aerobes CLINICAL MANIFESTATIONS: 1) Non-Limb-threatening Infections: * Superficial infection * Lack systemic toxicity * Minimal cellulitis (< 2 cm. Extension from portal of entry) * Ulcer-if present-doesnot penetrate fully thru skin * No bone or joint involvement * No underlying ischemia 2) Limb-threatening infections: * Extensive cellulitis (> 2 cm.) * Lymphangitis * Full-thickness ulcers * Frequent bone & joint infections * Ischemia + gangrene * Fever + * Deep plantar abscesses * Bacteremia + hematogenous spreading infections 3) Local Signs a) Infection • Prognosis affected by anatomic location + proximal infection • Along metatarsals Lower limb salvage • At heel higher mortality. • Above knee • Most Lower Limb infections begin as perforating ulcer Infection signaled by: * wormth * redness * swelling & purulent exudate * Tenderness minimal (?) Gas in soft tissues: * by crepitus or X rays * USU mixed infections – GNB & anaerobes * foul odour (tissue necrosis & anaerobic infect) * gangrene + (Infection or Ischemia) •Look for osteomyelitis & deep tissue destruction •Unroof all encrusted areas, so that :- * wound can be inspected carefully * you can assess extent of : - Deep tissue involvement - Bone & joint involvement •Importance of obtaining Deep tissue culture / bone •22% osteomyelitis diagnosed clinically •68% silent osteomyelitis by bone Bx & culture (JAMA : 266: 1246, 1991) b) Vascular disease * Intermittent claudication * pulse – bruit * shiny skin, reduced hair, nail growth * collapsed veins * use of doppler study c) Neuropathy * loss of protective pain sensation * L.L. & forefoot more affected * Assess pain, Temp., touch, propioception & DTR * Nylon monofilament test 4) Systemic S/Sx •USU late & indicate severe infection •Uncontrolled hyperglycemia – only reliable Sx. •Fever in case of pus containment •36% of patients with limb-threatening sepsis have temp. more than 37.8.c on Adm. Day. (infec. Dis. Clin.North Am. 9 : 143.1995) DIAGNOSIS: 1) Leukocytosis • Minimal / absent even with severe infection • 53% of patients with limb threatening infection have WBC more than 10,000 / mm3 (Inf. Dis. N. Am (: 143,1995) 2) ESR 3) Blood culture • Positive 10-15% but should be done in All patients • Higher yields in febrile patients 4) Wound or tissue cultures • Obtain deep tissue cultures • Avoid contact with surface ulcer and draining lession • Thus growing contaminant organisms avoided ** Ulcer swab 62% as correlated with ** Needle aspirate 69% result of deep tissue ** Ulcer base curretage 75% obtained at amputation (Rev. Infect Dis 6 *Suupl 1) S171, 1984) 5) Obtain both aerobic & anaerobi culture before ABX a) Debridement : Cult deep tissue including bone : Asp & Bx unexposed bone not advised b) Direct ulcer culture • Clean ulcer carefully with betadine • Allow to dry • Remove with alcohol • Remove overlying eschar • Insert swab through ulcer opening to obtain deep culture • Place in anaerobic transport needia,send quickly to lab. c) Indirect culture of ulcer base • Clean skin adjacent to ulcer with betadine • Insert needle thru intact skin, aiming at ulcer base • Aspirate material from ulcer base • You may inject sterile saline then aspirate and culture d) Aspirate bullae or fluctuant collections 6) Gram stain • Usu. Not helpful (revealing mixed flora) • However finding GP rods despite lacking inflam. response may indicate clostridial infection • This may rapidly progressive 7) Radiographs – osteomyelitis vs Diab. osteopathy • Sinugram • Indium labelled leulocytes – most sensitive for ocult osteomyelitis • CT Scan and MRI • Probing base of ulcer to detect bone MANAGEMENT Integrated multidisciplinary approach, involving internists/ diabetologist surgeons / orthopedics / constructive Podiatrician, ID Physicians Early surgical and infectious disease consultation Essential MEDICAL TREATMENT Antibiotics: Mainstay, recommended in presence of: • Surrounding cellulitis When Abx choice • Foul smelling lesion based on adequate • Fever culture, no single ABx • Deep tissue infection regimen being superior. EMPERIC ABX • Necessary pending culture results • Give full doses because poor penetration at infection site • Avoid nephrotoxic ABX whenever possible • Pts w/ advanced vascular disease need special attention to assure adequate dose at infection site a) Non limb threatening infections • Direct ABX at commonly offending microorganism (staph. & strep) • Outpation: clindamycin or cephalexin for 2 wks. • Pts w/ superficial ulcer w/ cellulitis requiring Hosp Administration and parenteral ABX -- cefazolin Modify according -- cefoxitin or Amp salbactam to culture results -- ticarcillin + BLI, tazocin or others b) Severe limb threatening infections • Offending organism usu. polymicrobial • Thus broad spectrum ABX use • In the past: “Triple ABX” Amp + genta + metronidasole / clinda • Authorities prefer avoiding AMG except when treating resistant pathogens • ABX options include: Tazocin (piperacillin – tazobactam) ceftriaxone + clinda / Metronidazote. • Enterococci: when isolated from deep culture, it maybe the offending agent esp. if no response to initial emperic therapy. Thus: choose ABX active against these microbes. c) Life threatening infections • Use broad spectrum ABX, better those active against enterococci till culture result obtained • Use imipenem or combination regim • AMG active against GNB, can be used with broad spectrum ABX pending culture results nephrotoxicity minimal w/ short course • In nosocomial infection remember MRSA, thus vancomycin use till culture reported ABX adjustment according to deep culture results a) Pt responding clinically while ABX used not active against specific isolate from deep culture. What to do? • Continue same eperic ABX started with • Isolated pathogen may just be coloniser • This isolate needs no directed ABX b) Bacteria isolated resistant to current ABX and pt not responding clinically • Extend ABX regime to cover isolated pathogens • In seriously infected pts. Use of broad spectrum ABX that appear unnecessary maybe unavoidable Duration of Antibiotic Therapy • Optimal duration not well established • Osteomyelitis: 6-12 wks, esp if infected bone not removed • Infection limited to soft tissue: 10-14 days IV if pt responding well, use p.o. therapy to complete 2 wks • Non limb threatening - 2 wks po therapy aimed at acute cellulitis - continued ulcer care depends on local wound care and further ABX unnecessary - foot infec. w/ secondary bacteremia usu. Staph or bacteroides spp. (prolonged ABX required. - prolonged ABX course + I & D may spare amputation, but early surgical intervention usu. Needed to = control sepsis Emperic ABX for Diabetic Foot Infection • Non-limb threatening infection - Oral Regimen * cephalexin * Clindamycin * Dicloxacillin * Amoxicillin – Clavulanate (Augmention) - Parenteral Regimen * Cefazolin * Oxacillin or nafcillin * Clindamycin * Life Threatening Infection • Parenteral Regimen * Imipenem – Cilastin * Vancomycin + metronidazole + aztreonam * Amp salbactam + AMB * Tazocin + AMG PREVENTION An ounce of prevention is worth a pound of care Diabetic foot infection better prevented than treated * regular feet exam neuropathy, vasculopathy * Pt education *** smoking, daily self exam of feet, extreme temp, early medical advice, no barefoot, proper footwear, wt. Control, foot skin lubrication * Early intervention, eg. Surgical, revascularization, etc * Treat superficial infections early (eg. nail infections and paronychia)