Big Group Discussion Group C3B Malig-Marayag Facial Cellulitis in a Diabetic Patient: M.E. (55 y/o male) Chief complaint: Painful erythematous swelling on the face HISTORY OF PRESENT ILLNESS 3 days PTA appearance of a papule about the size of munggo seed over the border of the left lower lip; no fever, no accompanying pain, erythema, swelling no other symptoms No medications taken. No consult was done. 2 days PTA Increase in size of the papule with central suppuration, sorrounding erythematous plaque, swelling of the left half of the lower lip and mild pain fever (Tmax- 38.5C) and generalized body malaise Self medicated with Amoxycillin 500mg tab BID and Paracetamol 500mg/tab 1tab OD which provided minimal relief HISTORY OF PRESENT ILLNESS 1 day PTA Progression of swelling involving the entire lower lip, left cheek, left periorbital region and submandibular area Consultation at a nearby community center and was advised to go a hospital. Few hours PTA Further swelling on the left side of the face accompanied by severe pain admission PAST MEDICAL HISTORY Diabetic for 27 years Maintained on Gliclazide(Diamicron) for the first 10 years with unrecalled dose taken OD Insulin maintenance (Humulin N 20 u in the morning and 15 u in the evening) for the past 16 years Cholecystitis- underwent cholecystectomy in 1996 Underwent 3 operations for the right eye: cataract surgery glaucoma- trabeculectomy corneal transplant; patient developed Graft Versus Host Disease which led to blindness FAMILY HISTORY (+) DM mother (+) HPN - father (+) HPN brother (-) Cancer, allergy, stroke PERSONAL AND SOCIAL HISTORY Married (with 2 children) Used to work as a master cutter at a tailoring shop but is currently unemployed Occasionally smokes and drinks alcohol Mixed diet MEDICATIONS Insulin (Humulin N 20 U in the morning and 15 U in the evening) Vitamin B complex REVIEW OF SYSTEMS No headache, vertigo, syncope No epistaxis, nasal discharge No neck stiffness, masses, lymphadenopathy No tinnitus, ear discharge, loss of hearing No dyspnea, cough No chest pain, easy fatigability, nocturnal dyspnea, orthopnea, palpitations REVIEW OF SYSTEMS No nausea, vomiting, hematemesis, dysphagia, abdominal pain, diarrhea, constipation, melena, hematochezia No urinary urgency, dysuria, flank pain, urethral discharge No joint stiffness, pain, swelling, muscle pain, cramps, weakness, wasting (+) hyperpigmented scaly plaque on the dorsum of the right foot No heat-cold intolerance No pallor, abnormal bleeding, bruising PHYSICAL EXAMINATION Conscious, coherent and oriented to time, place and person Vital Signs: BP: 120/80mmHg PR - 90bpm, RR-24cpm, Temp: 37.3C Weight= 66 kg Height= 170cm BMI=23 HEENT: (+) periorbital swelling, nonhyperemic conjunctivae, anicteric sclerae, cornea opaque No nasoaural discharge, (+) swelling with violaceous discoloration of the lower lip and sorrounding skin topped with multiple erosions, crusts and pus, buccal mucosa cannot be assessed NECK: supple neck, no masses, (-) palpable cervical LN,right, LN on the left cannot be assessed due to swelling over the submandibular area, (-) neck vein distension PHYSICAL EXAMINATION THORAX & LUNGS: Symmetric chest expansion, (-) retractions (-) lagging, equal vocal tactile fremiti, resonant on all lung fileds, clear breath sounds CARDIAC: Adynamic precordium, (-) heaves, thrills and lifts, S1>S2 at the apex, S2>S1 at the base, (-) murmurs Pulses full and equal on all extremities ABDOMEN: soft, globular abdomen, non-tender, normoactive bowel sounds; Liver-smooth, non-tender, vertical span- 6 cm at the MCL; spleen & kidneys not palpable EXTREMITIES: Motor strength grade 5/5 on all extremities, no sensory deficits (+)pruritic, hyperpigmented plaque with scaly surface on the dorsum of the right foot CLINICAL IMPRESSION Facial cellulitis in a patient with type 2 diabetes mellitus DIFFERENTIAL DIAGNOSIS Cellulitis Erysipelas Cellulitis vs Erysipelas CellulitisErysipelas EtiologyStaphylococcus spp. Streptococcus spp. Various other bacteria Streptococcus pyogenes Characteristics of lesionLocalized pain, erythema, swelling, heat, lesion is not raised, line between the involved and uninvolved tissue is indistinct Local redness, heat, swelling with a characteristic raised, indurated border Accompanying signs and symptoms Malaise, chills, feverMalaise, chills, high fever, headache, vomiting, joint pains Harrisons Principles of Internal Medicine 17 th ed. CELLULITIS Cellulitis Acute suppurative inflammation involving the subcutaneous tissue Characterized by: Localized pain, erythema, swelling, heat Differentiated from erysipelas: Lesion is not raised Line between the involved and uninvolved tissue is indistinct Harrisons Principles of Internal Medicine, 17 th ed. Jawetz, Melnick & Adelburgs Medical Microbiology, 24 th ed. Cellulitis Mild local erythema and tenderness Rapidly becomes intense and spreads Area becomes infiltrated and pits on pressure Central part may become nodular and develop a vesicle that ruptures and discharges pus and necrotic material Malaise Fever and chills Andrews Diseases of the Skin: Clinical Dermatology, 10 th ed. Cellulitis Most commonly caused by indigenous flora Staphylococcus aureus usually associated with an abscess, folliculitis, or foreign body Streptococcus pyogenes spreads more rapidly; associated with fever and lymphangitis Bacteria may gain access to the epidermis through: Cracks in the skin, abrasions, cuts, burns, insect bites, surgical incisions, intravenous catheters Harrisons Principles of Internal Medicine, 17 th ed. Cellulitis Associated with predisposing conditions Streptococcus agalactiae diabetes mellitus, peripheral vascular disease Haemophilus influenzae causes periorbital cellulitis children with sinusitis, otitis media or epiglottitis Harrisons Principles of Internal Medicine, 17 th ed. Infections in Diabetics Diabetic patients have greater frequency and severity of infection due to: Diminished vascularization Hyperglycemia Impairs killing of micro-organisms by neutrophils and macrophages Interferes with T lymphocyte function Aids in colonization and growth of a variety of organisms (Candida and other fungal species Harrisons Principles of Internal Medicine, 17 th ed. Oxford Textbook of Medicine, 4 th ed. DIAGNOSTIC PLANS FOR DM CBC CBG Blood Chemistry creatinine Lipid profile HBA1c Sodium Potassium Arterial Blood Gas Laboratory Results pH 0.05 pCO227.6 mmHg40 5 pO256.5 mmHg95 5 HCO319.5 mmol/L24 2 dFiO221.84% P/F269 DIAGNOSTIC TEST FOR DIABETES MELLITUS National Diabetes Group and WHO diagnostic criteria for DM: Fasting plasma glucose level at or above 126 mg/dL (7.0 mmol/L). Plasma glucose at or above 200 mg/dL (11.1 mmol/L) two hours after a 75 g oral glucose load as in a glucose tolerance test. Symptoms of hyperglycemia and plasma glucose at or above 200 mg/dL (11.1 mmol/L). Harrisons 17 th Edition Fasting blood glucose test The most common test for diagnosis of diabetes. blood glucose levels are checked after fasting for between 12 and 14 hours. Patients with fasting glucose levels from 100 to 125 mg/dL (6.1 and 7.0 mmol/L) are considered to have impaired fasting glucose Patients with diabetes may be asked to delay their diabetes medication or insulin dose until the test is completed. Random blood glucose test blood glucose levels are checked at various times during the day, and it doesnt matter when you last ate. Blood glucose levels tend to stay constant in a person who doesnt have diabetes. Oral glucose tolerance test (OGTT) FBS is obtained before the ingestion of a 50- to 200-g glucose load (usual amount is 75 g), blood samples are drawn at , 1, 2, and 3 hours (may be 4- or 5-hour sampling). Blood samples are checked at regular intervals for two hours. Glucose tolerance tests are used when the results of the fasting blood glucose are borderline. They are also used to diagnose diabetes in pregnancy (gestational diabetes). NORMAL: the results of the glucose tolerance test will show that their blood sugar levels fall within the normal range Patients with plasma glucose at or above 140 mg/dL or 7.8 mmol/L, but not over 200, two hours after a 75 g oral glucose load are considered to have impaired glucose tolerance.impaired glucose tolerance Glycated Hemoglobin (Glycohemoglobin, HbA1c) for Diabetes Mellitus Measures glycemic control over a 60- to 120-day period by measuring the irreversible reaction of glucose to hemoglobin through freely permeable erythrocytes during their 120-day lifecycle. While not used for diagnosis, an elevated level of glucose irreversibly bound to hemoglobin of 6.0% or higher (the 2003 revised U.S. standard) is considered abnormal by most labs GOALS OF THERAPY Eliminate symptoms related to hyperglycemia Reduce or eliminate the long-term microvascular and macrovascular complications of DM Allow the patient to achieve as normal a lifestyle as possible Harrisons 17 th Edition Insulin vs. hypoglycemics Oral hypoglycemics Should not be used in severly ill patients with type 2 DM Insulin secretagogues: such as sulfonlyureas are effective in individual with relatively recent onset ( 133umol/L (1.5mg/dL) in men] Should be discontinued in patients who are severly ill, in patients who can take nothing orally and in thoe receiving radiograohic contrast material - glucosidase inhibitors (acarbose and miglitol): should not be used in patients with inflammatory bowel disease, gastroparesis or a serum creatinine >177umol/L (2.0mg/dL) Insulin Considered initial therapy in type 2 DM, particularly in lean individuals or those with severe weight loss, in individuals with underlying renal or hepatic disease that precludes oral glucose-lowering agents, or in individuals who are hospitalized or acutely i ll A long acting insulin (lantus) is best for the patient because if his age etc. since you dont have to take it often. Patient education about DM, nutrition and exercise Patient with DM should receive education about: Nutrition Exercise Care of diabetes during illness Medications to lower the plasma glucose Continuing process with regular visits for reinforcement Diabetes self-management education (DSME) Harrisons 17 th Edition Diabetes education Self-monitoring of blood glucose Urine ketone monitoring (type 1) Insulin administration Guidelines for diabetes management during illness Management of hypoglycemia Foot and skin care DM management before, during and after exercise Risk-factor-modifying activities Harrisons 17 th Edition Nutrition Medical Nutrition Therapy (MNT) Modest caloric reduction Reduced fat intake Increased physical activity Reduction of hyperlipidemia and hypertension Harrisons 17 th Edition Exercise CV risk reduction Reduced BP Maintenance of muscle mass Reduction in body fat and weight loss Lowering plasma glucose Increasing insulin sensitivity *ADA recommends 150 min/week (distributed over at least 3 days) Harrisons 17 th Edition Monitoring the level of glyceminc control Plasma glucose measurements by the patient and assessment of long-term control by the physician Measurement of A1C and review of the patients self- measurement of plasma glucose Harrisons 17 th Edition Self-monitoring of Blood Glucose Standard of care in diabetes management and allows the patient to monitor his/her blood glucose at any time Glucose monitors can rapidly and accurately measure glucose in small amounts of blood (3-10 L obtained from the fingertip *individuals with type 2 DM who are taking insulin should utilize SMBG more frequently than than those on oral agents Harrisons 17 th Edition Assessment of Long-term Glycemic Control Measurement of glycated hemoglobin Plasma glucose is consistently elevated = increase in nonenzymatic glycation of hemoglobin Reflects the glycemic history over the previous 2-3 months Harrisons 17 th Edition CELLULITIS DIAGNOSTIC PLANS FOR CELLULITIS CT scan with contrast of the paranasal and neck area pharyngolaryngoscopy Blood culture Aspiration CT scan *As clinically indicated; Ulcerated lesions should be cleaned and debrided before having wound base swabbed; Most useful if vesicle/bullae or fluid abscess present; Seek out bone trauma and air fluid levels; Indications neurological deficits, vision nonassessable, proptosis/deteriorating acuity or colour/bilateral edema/ophthalmoplegia, no improvement after 24 h and swinging pyrexia not resolving within 36 h (for head only); **Only if central nervous system involvement suspected Diagnosis Based on appearance of the skin and patient history Drainage from an abscess or weeping wound associated with cellulitis should be sent for culture and sensitivities. Material from needle aspiration of inflamed skin or skin biopsy can be cultured in cases of cellulitis without purulence, abscess, or a necrotic Indications for blood cultures include significant fever and chills, severe immunocompromise, periorbital cellulitis, and cellulitis superimposed on lymphedema. A polymorphonuclear leukocytosis is often present with cellulitis; a complete blood cell count and differential may help gauge the severity of infection and the hematologic response. Goals of treatment Eliminate the offending microorganism Treat/manage any underlying conditions that would increase the chance of cellulitis returning (DM) Prevent recurrence of cellulitis oral therapy for mild infections intravenous therapy for severe infections achievement of high drug levels with rapid delivery. Therapeutic approach Non-pharmacologic Rest affected area, elevate the area of the body involved (this will help decrease swelling and relieve discomfort) Clean wound site Pharmacologic Cellulitis in a DM patient Early or Mild disease Augmentin 875 mg PO bid Second Generation Cephalosporin (cefoxitin, cefacor, cefuroxime) Third Generation Cephalosporin (cefotaxime, ceftazidime,m ceftriaxone, cefixime) Severe disease Imipenem-Cilastatin (Primaxin) Ampicillin-sulbactam Meropenem Trovafloxacin IV Nafcillin 2 g IV every 4 hours Oxacillin 2 g IV every 4 hours Vancomycin g IV qd (ABG) Linezolid In a study by Kohno et al, Linezolid was compared with vancomycin; both had a comparable clinical success rate in the treatment of SSTi. In the lab tests done after the end of the treatment and during follow up, Linezolid had a better microbial eradication rate. Also, for the adverse effects (hematologic), linezolid was safer. S. Kohno1, K. Yamaguchi2, et al. Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant. Staphylococcus aureus in Japan. Journal of Antimicrobial Chemotherapy (6): ; doi: /jac/dkm369 Vancomycin is distributed widely to various tissues and body fluids, however in patient with DM, its penetration in soft tissues is greatly impaired AUSkhirtladze K; Hutschala D; Fleck T; Thalhammer F; Ehrlich M; Vukovich T; Muller M; Tschernko. Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. EM SOAntimicrob Agents Chemother Apr;50(4): a8X1QFoqoQSyT&refNum=8a8X1QFoqoQSyT&refNum=8 In a study by Stein et al, Linezolid was effective in the treatment of Staphylococcus aureus in diabetic patients G E. Stein1,* S Schooley1, et al. Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections. Journal of Antimicrobial Chemotherapy, doi: /jac/dkm271 Duration of therapy response to drug therapy follow-up is of utmost importance 10 to 14 days of antibiotic therapy Absence of response/worsening after five days of the initiation of therapy prompts a change in the antibiotic regimen or other investigations to verify the diagnosis Preventing a recurrence of cellulitis Cellulitis tends to recur in people with certain medical conditions that can lead to skin breakdown, such as edema (fluid buildup), fungal or bacterial infections, diabetes, or peripheral arterial disease. edema, support stockings and good skin hygiene may reduce or eliminate recurrence of cellulitis. fungal infections, regular use of antifungal medicines may help reduce recurrent cellulitis. high risk for recurring cellulitis, (when with open wound or cut) taking preventive antibiotics may help Linezolid versus Vancomycin in Treatment of Complicated Skin and Soft Tissue Infections John Weigelt,* Kamal Itani,Dennis Stevens, William Lau, Matthew Dryden, Charles Knirsch,* and the Linezolid CSSTI Study Group Introduction Skin and soft tissue infections (SSTIs) are a common cause of morbidity in both the community and the hospital. An SSTI is classified as complicated if: the infection has spread to the deeper soft tissues surgical intervention is necessary the patient has a comorbid condition hindering treatment response (e.g. DM or HIV) Purpose The purpose of this study was to compare linezolid to vancomycin (clincial and microbiological efficacies, safety and tolerability) in the treatment of suspected or proven methicillin-resistant gram-positive complicated SSTIs (MRSA CSSTIs) requiring hospitalization. Background of the Study This was a randomized, open-label, comparator-controlled, multicenter, multinational study that included patients with suspected or proven methicillin-resistant Staphylococcus aureus (MRSA) infections that involved substantial areas of skin or deeper soft tissues, such as cellulitis, abscesses, infected ulcers, or burns Vancomycin Microbiological Efficacy Linezolid > Vancomycin Safety and Tolerability Linezolid = Vancomycin Risk Factors Patient RelatedTreatment Related Known colonization Immunosuppression Diabetes open chronic wounds increased illness severity previous antibiotic use intravascular catheterization prolonged hospitalization Linezolid AdvantagesDisadvantages 100% oral bioavailability: Allows early switch from IV to oral antibiotics Longer treatment duration Selectively binds to 50S ribosome: Prevents cross- resistance with other antibiotics Increased risk for thrombocytopenia Cheaper Cost Linezolid Vancomycin IVZyvox 2mg/mL x 300mL P 3, Vancocin 500mg P 1, SuspensionZyvox 100 mg/5 mL x 150 mL P 14, NA TabletZyvox 600mg P 2, NA LinezolidVancomycin 600mg IV or PO every 12 hours IV: 3, x 2 = P 6, PO: 2, x 2 = P 5, g IV every 12 hours IV: 1, x 4 = P 7,716 References Vincent Ki, MD and Coleman Rotstein, MD. Bacterial skin and soft tissue infections in adults: A review of their epidemiology, pathogenesis, diagnosis, treatment and site of care. Can J Infect Dis Med Microbiol March; 19(2): G E. Stein1,* S Schooley1, et al. Linezolid tissue penetration and serum activity against strains of methicillin-resistant Staphylococcus aureus with reduced vancomycin susceptibility in diabetic patients with foot infections. Journal of Antimicrobial Chemotherapy, doi: /jac/dkm271 AUSkhirtladze K; Hutschala D et al. Impaired target site penetration of vancomycin in diabetic patients following cardiac surgery. EM SOAntimicrob Agents Chemother Apr;50(4): S. Kohno1, K. Yamaguchi2, et al. Linezolid versus vancomycin for the treatment of infections caused by methicillin-resistant. Staphylococcus aureus in Japan. Journal of Antimicrobial Chemotherapy (6): ; doi: /jac/dkm369