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Sepsis In A Young Physician

Sepsis In A Young Physician. March 31, 2004 Edward L. Goodman, MD. Outline. Case Presentation Differential Diagnosis Hospital Course Epidemiology Adjunctive Therapy. History. CC: Fever and myalgias HPI: 40 year old neurologist Six days of progressive large muscle myalgias

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Sepsis In A Young Physician

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  1. Sepsis In A Young Physician March 31, 2004 Edward L. Goodman, MD

  2. Outline • Case Presentation • Differential Diagnosis • Hospital Course • Epidemiology • Adjunctive Therapy

  3. History • CC: Fever and myalgias • HPI: 40 year old neurologist • Six days of progressive large muscle myalgias • Three days of mild cough mildly productive • Mild dyspnea, no pleurisy • Self administered amantadine for presumed influenza

  4. History 2 • ROS: no recent sore throat, no CNS symptoms, no GI or GU sx • PMH: unremarkable except for frequent flu like illnesses for which he takes amantadine and NSAIDs • Epidemiology: twins age 15 month, not in daycare, recent travel to California where exposed to two other young children

  5. Exam • Very ill and toxic appearing • Temp very elevated, HR 120, BP 115/73 • Injected conjunctivae without petechiae • Supple neck • Diffuse erythema on trunk • Few petechiae on legs • Few rales LLL, gallop rhythm • Tender muscles

  6. Initial Chest X Ray

  7. Initial Lab • pH 7.4, pCO2 33.8, pO2 58 on RA • Mixed acid base disorder • WBC 8500, 53% bands • Platelets 158,000 • INR 1.7, PTT 48.7, d dimer 537 • Creat 1.0, Alk ptase 173, AST/ALT 48/121, Bili 3.7 (direct 2.6), CRP 23.1

  8. Differential Diagnosis • Focal infiltrates - Community Acquired Pneumonia, post influenza pneumonia • Severe Myalgias • Influenza: proper season • Dengue: no travel to tropics • Leptospirosis: no exposure to rats, cattle, dogs • Petechiae, septic, infiltrate: • meningococci

  9. Hospital Course • Started on Ceftriaxone and Moxifloxacin for possible CAP, meningococcemia • Transfer to ICU for deteriorating BP, pulmonary status • Blood cultures positive at 12 hours for GPC in pairs and chains = likely Strept pneumo?

  10. Next Day: 2/23/04 • 0600 blood cultures are beta hemolytic • Not Strept pneumo! • One dose Vancomycin • Added Clindamycin • Started Xigris • On vent 100% FiO2 • Multiple pressors • Survival seems unlikely

  11. Third Day: 2/24/04 • Group A Strept confirmed • Added IVIG • Multiple pressors and 100% FiO2 still • Cardiac arrest – resuscitated • Hung crepe with family

  12. Subsequent CXR2/26/04

  13. Subsequent Course • Blisters on leg develop and evolve • Vascular surgeon recommends against debridement • Gradually rallies • Pressors tapered • Vent tapered • MOF reversed • Discharged to Rehab 3/15/04 • Home 3/22/04!

  14. Initial Lab • pH 7.4, pCO2 33.8, pO2 58 on RA • Mixed acid base disorder • WBC 8500, 53% bands • Platelets 158,000 • INR 1.7, PTT 48.7, d dimer 537 • Creat 1.0, Alk ptase 173, AST/ALT 48/121, Bili 3.7 (direct 2.6), CRP 23.1

  15. Peak Lab Abnormalities

  16. Skin Lesions First Day

  17. Evolving Lesions

  18. Desquamation Day 16

  19. Recent Film: 3/8/04

  20. Epidemiology of Invasive GSS

  21. Epidemiology

  22. Discussion • Antibiotics • Penicillin • Clindamycin • Role of IVIG

  23. Penicillin’s ineffectiveness • High mortality in invasive GAS when Penicillin used • 81% mortality in myositis • Animal data on inoculum effect • High concentrations of GAS in deep sites • Stationary phase reached quickly • PBPs not expressed in stationary phase

  24. Clindamycin • No inoculum effect • Suppresses toxin synthesis • Facilitates phagocytosis by inhibiting M protein synthesis • Suppresses proteins involved in cell wall synthesis • Longer post antibiotic effect (PAE) • Suppress LPS induced monocyte synthesis of TNF-alpha

  25. TSS and IVIG • Shock from gram positive toxins • Superantigens • Enterotoxins • TSST-1 • SPEA • Superantigens bind to • MHC II • ß chain of T cell receptor • Resulting in • T cell proliferation • Cytokine production

  26. IVIG • Blocks in vitro T cell activation • Contains superantigen neutralizing antibodies

  27. Effects of IVIGKaul et al, CID 1999;28:800

  28. Conclusion • Severe pain and fever – think of GAS • Know the epidemiology of your institution • Consult a surgeon promptly if skin or muscle involvement • Add Clindamycin to beta lactam therapy for necrotizing or serious GAS infections • Consider IVIG for TSS • Consider Xigris

  29. References • Bisno AL, Stevens DL. Streptococcal Infections of Skin and Soft Tissues. New Eng J Med 1996; 334:240-245. • Case Records of the MGH. New Eng J Med 1995; 333: 113-119. • Case Records of the MGH. New Eng J Med 2002; 347:831-837. • Disease Prevention News. TDH. March 27, 2000;60: No.7. • Kaul R, McGeer A et al. Intravenous Immunoglobulin Therapy for Streptococcal Toxic Shock Syndrome – A Comparative Observational Study. Clin Infect Dis 1999; 28:800-807.

  30. References - continued • Kazatchkine MD, Kaveri, SV. Immunomodulation of Autoimmune and Inflammatory Diseases with Intravenous Immune Globulin. New Eng J Med 2001; 345: 747-755. • Stevens DL. The Flesh-Eating Bacterium: What’s Next. J Infect Dis 1999;179(Suppl 2): S366-374

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