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 CXR 2/26/04
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 Abnormalities
Test Result Date
WBC Platelets PTT Creat Bili AST ALT Alk phos
32,600 62,000 120.9 3.6 6.4 309 502 523
3/01/04 2/27/04 2/24/04 2/28/04 2/27/04 3/11/04 3/12/04 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 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 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