sepsis in a young physician march 31, 2004 edward l. goodman, md
TRANSCRIPT
Sepsis In A Young Physician
March 31, 2004
Edward L. Goodman, MD
Outline
• Case Presentation
• Differential Diagnosis
• Hospital Course
• Epidemiology
• Adjunctive Therapy
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
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
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
Initial Chest X Ray
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
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
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?
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
Third Day: 2/24/04
• Group A Strept confirmed
• Added IVIG
• Multiple pressors and 100% FiO2 still
• Cardiac arrest – resuscitated
• Hung crepe with family
Subsequent CXR2/26/04
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!
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
Peak Lab AbnormalitiesTest 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
Skin Lesions First Day
Evolving Lesions
Desquamation Day 16
Recent Film: 3/8/04
Epidemiology of Invasive GSS
Epidemiology
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 IVIGKaul et al, CID 1999;28:800
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
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