Sepsis In A Young Physician

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Sepsis In A Young Physician

• March 31, 2004
• Edward L. Goodman, MD

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Outline

• Case Presentation
• Differential Diagnosis
• Hospital Course
• Epidemiology
• Adjunctive Therapy

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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

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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

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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

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Initial Chest X Ray
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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

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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

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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?

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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

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Third Day 2/24/04

• Group A Strept confirmed
• Added IVIG
• Multiple pressors and 100 FiO2 still
• Cardiac arrest resuscitated
• Hung crepe with family

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Subsequent CXR2/26/04
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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!

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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

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Peak Lab Abnormalities
Test Result Date
WBC 32,600 3/01/04
Platelets 62,000 2/27/04
PTT 120.9 2/24/04
Creat 3.6 2/28/04
Bili 6.4 2/27/04
AST 309 3/11/04
ALT 502 3/12/04
Alk phos 523 3/12/04

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Skin Lesions First Day
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Evolving Lesions
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Desquamation Day 16
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Recent Film 3/8/04
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Epidemiology of Invasive GSS
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Epidemiology
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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 if skin or muscle
  involvement
• Add Clindamycin to beta lactam therapy for
  necrotizing or serious GAS infections
• Consider IVIG for TSS
• Consider Xigris

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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