A Case of Toxic Shock?

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A Case of Toxic Shock?

• Edward L. Goodman, MD
• September 18, 2002

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Outline

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

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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

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History 2

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

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Exam

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

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Imaging
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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 gt1000
Creat 2.2 3.0
Anti DNAse B 1960
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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

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RR 297 (95 CI 14 - 6000)plt0.001
Exposed to the suspect group of HCWs Unexposed to suspect group
Infected with epidemic strain 10 0
Uninfected 3 49
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Epidemiology - continued

• Multivariate analysis
• No relationship to sex, type of wound or
  underlying condition
• Age gt60 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

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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!

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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!

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Imaging
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Hoadley DJ, Case Records of the MGH, NEJM
2002347831-839
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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

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Discussion

• Antibiotics
• Penicillin
• Clindamycin
• Role of IVIG

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Penicillins 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

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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

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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

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IVIG

• Blocks in vitro T cell activation
• Contains superantigen neutralizing antibodies

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Effects of IVIGKaul et al, CID 199928800
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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

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References

• Bisno AL, Stevens DL. Streptococcal Infections of
  Skin and Soft Tissues. New Eng J Med 1996
  334240-245.
• Case Records of the MGH. New Eng J Med 1995 333
  113-119.
• Case Records of the MGH. New Eng J Med 2002
  347831-837.
• Disease Prevention News. TDH. March 27, 200060
  No.7.
• Kaul R, McGeer A et al. Intravenous
  Immunoglobulin Therapy for Streptococcal Toxic
  Shock Syndrome A Comparative Observational
  Study. Clin Infect Dis 1999 28800-807.

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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 Whats
  Next. J Infect Dis 1999179(Suppl 2) S366-374