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A Case of Toxic Shock?

A Case of Toxic Shock?. Edward L. Goodman, MD September 18, 2002. Outline. Case Presentation Relevant Epidemiology Differential Diagnosis Pathophysiology Management. Case Presentation. July 18, 2002 CC: SOB, Hypotension, Dizzy

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A Case of Toxic Shock?

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  1. A Case of Toxic Shock? Edward L. Goodman, MD September 18, 2002

  2. Outline • Case Presentation • Relevant Epidemiology • Differential Diagnosis • Pathophysiology • Management

  3. Case Presentation • July 18, 2002 • CC: SOB, Hypotension, Dizzy • HPI: 74 WM two day hx of chills, fever, SOB and weakness. Tender in right thigh • GERD surgery 5/6/02 complicated by necrotizing pancreatitis and open wound after laparotomy • Wound Care Department managing open wound as outpatient

  4. History 2 • PMH • IDDM • HBP • PUD • Hyperlipidemia, • Diverticulosis • Prostate Ca S/P XRT and Lupron

  5. Exam • Alert but confused • BP 80’s, tachycardia • Healing open abdominal wound • Faint, generalized erythema • Tender demarcated erythema swollen right thigh • Tinea pedis

  6. Imaging

  7. Lab Results

  8. Epidemiology • 2001 Outbreak Group A Streptococcal infections of complex wounds • 28 cases/10 isolates were available and typed • Epidemic strain identified • Identical emm (M protein) type • Levofloxacin/clindamycin resistant • Virtually all patients had been on these drugs • 52 control patients selected to compare with 10 cases

  9. RR 297 (95% CI 14 - 6000)p<0.001

  10. Epidemiology - continued • Multivariate analysis • No relationship to sex, type of wound or underlying condition • Age >60 related • Thus, strong link to exposure to a specific group of HCW • Subsequent extensive HCW cultures negative • Implicated group • Many others • Epidemic ceased July 2001

  11. Epidemiology - continued • July 12, 2002 first case of GAS infection of a complex wound in 12 months • Four suspected HCW cultured again • One grew GAS from two sites - asymptomatic • One environmental isolate positive • All four isolates were identical but different M type from 2001 strain • Our patient was exposed to the implicated HCW!

  12. Initial Therapy • Received Cefotaxime by ER staff • Admitting Team started IV Pen G and Clindamycin • IVIG daily x 5 days • Vigorous support • Surgery consulted early and often • No surgery required!

  13. Imaging

  14. Hoadley DJ, Case Records of the MGH, NEJM 2002;347:831-839

  15. Discussion • Was there reason to infer a GAS etiology? • Clinical appearance • Relevant epidemiology • (No cultures were positive for GAS) • Strongly positive anti DNAse B suggests recent or current infection • Did he have invasive GAS infection? • Did he have features of GAS TSS? • See Case Definition

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

  17. 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

  18. 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

  19. 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

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

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

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

  23. 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.

  24. 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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