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

2. Outline Case Presentation Differential Diagnosis Pathophysiology
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 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

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 ) p<0.001
Exposed to the suspect group of HCWs
Unexposed to suspect group
Infected with epidemic strain 10
Uninfected 3 49

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

18. 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

21. Discussion
Antibiotics
Penicillin
Clindamycin
Role of IVIG

22. 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

23. 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

24. 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

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

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

30. 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

31. References
Bisno AL, Stevens DL. Streptococcal Infections of Skin and Soft Tissues. New Eng J Med 1996; 334:
Case Records of the MGH. New Eng J Med 1995; 333:
Case Records of the MGH. New Eng J Med 2002; 347:
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:

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