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

http://content.nejm.org/content/vol344/issue10/images/large/01f1.jpeg

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