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

Outline Case Presentation Differential Diagnosis Pathophysiology Relevant Epidemiology Differential Diagnosis Pathophysiology Management

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

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

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

Imaging

Lab Results 7/18/02 7/19/02 7/22/02 Hgb/Hct 12.0/36.1 WBC 24.7 Platelets 334,000 Protime 22.0 D Dimer >1000 Creat 2.2 3.0 Anti DNAse B 1:960

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

RR 297 (95% CI 14 - 6000) p<0.001 Exposed to the suspect group of HCWs Unexposed to suspect group Infected with epidemic strain 10 Uninfected 3 49

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

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!

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!

Imaging

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

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

Discussion Antibiotics Penicillin Clindamycin Role of IVIG

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

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

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

IVIG Blocks in vitro T cell activation Contains superantigen neutralizing antibodies

Effects of IVIG Kaul et al, CID 1999;28:800

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

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.

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