1. ID Case Conference Yvonne L. Ballard, MD 30 January 2008

2. CC: Fatigue, Shortness of Breath 49yo CM had a URI 2-3 weeks PTA. Sx included rhinorrhea, cough, malaise. Sx lasted one week, and resolved. 4 days PTA, recurrent sx developed. 2 days PTA, pt presented to PCP, who performed a rapid flu test, which was positive. Pt treated with Tamiflu, which he started to take immediately. Sx progressed, and pt called EMS for severe fatigue and difficulty breathing

3. PMH: None PSurgHx: Appendectomy, age 23 All: NKDA Meds: Nicorette gum SocHx: Lives with wife in CH 4 healthy children Ages 7, 9, 14, 17 Installs closets Chewed tobacco Occ. Beer No illicits FamHx: Mom, dec, Pancreatic CA Dad, alive, healthy Brother, alive, healthy Brother, alive, Colon CA

4. Physical Exam T 36.0, P 130s, BP 157/73, RR 33 WD, WN ill man; intubated, sedated NCAT, Pupils dilated, minimally reactive Tachycardic, Reg rhythm, no m/g/r BS coarse bilaterally, diffuse Abd soft, NT, ND, NABS Skin: diffuse maculopapular rash on head, trunk, and extremities Ext: no c/c/e. Cool extremities

5. Labs D-dimer 3397 Fibrinogen 857 AT III activity 49% BNP 33,187 CK 551, MB 24, Trop (–) PT 35, PTT 53, INR 2.6 Lactate 7.3 ABG 6.93/66/44/58% Etoh Screen Negative 117 4.4 91 13 60 6.8 57 4.375 192 5.4 34.1 240 11.9 1.3 4.5 8.1

7. Micro Data Urine Culture - Negative HIV ELISA - Negative RPR - NR RMSF Serologies - Negative CMV PCR - Negative Skin Lesion HSV 1 and 2 PCR - Negative EBV Serologies – Indicate previous exposure

8. Discussion…

9. Streptococcus pyogenes

10. Hospital Course Intubated in the ED Started on Vanc, Zosyn, Levaquin Levophed, Vasopressin, Phenylephrine Bicarb gtt, IVF boluses Three central lines placed Multiple modes of ventilation failed Worsening CXR Propofol gtt PEA Arrest…Successful code Family consented for ECMO

11. Hospital Course, cont. Pt desats to 40s while en route to SICU Prep for ECMO begins Pt goes into Asystole Resuscitation unsuccessful Pronounced dead at 2:01 am, after 20 minute code

12. Micro Data Blood Culture, 4/4 bottles positive: Streptococcus pyogenes (Group A Strep) Induced sputum – Group A Strep Right Lung Biopsy – Group A Strep Right Lung Biopsy – Viral Cx Negative Right Lung Biopsy – CMV PCR Negative

13. Micro Data Group A Strep Sensitivity Testing Penicillin G (MIC 0.032) Vancomycin (MIC 1) Levofloxacin (MIC 0.5) Erythromycin (sens) Clindamycin (sens)

14. Group A Streptococcus Aerobic gram + coccus pairs and chains Catalase negative Beta-hemolytic on blood agar Growth inhibited by bacitracin

15. GAS Disease Manifestations

16. Virulence Factors M protein Filamentous protein on cell membrane; has antiphagocytic properties Types 1, 3, 12, and 28 most common in shock Pts with decreased serum antibodies to M prot more susceptible to invasive infections Exotoxins Pyrogenic exotoxins A, B, and C; SSA, MF Cause cytotoxicity, pyrogenicity, and enhances lethal effects of endotoxins

17. Streptococcus pyogenes Clinical presentations: Pharyngitis, Sinusitis, Otitis Media Skin and soft tissue infections Impetigo, Erysipelas, Localized cellulitis Invasive Disease Bacteremia Necrotizing Fasciitis, Gangrenous Myositis Pneumonia Toxic Shock Syndrome

20. Diagnosis of STSS Isolation of GAS from normally sterile site AND Hypotension PLUS evidence of organ failure (at least 2) Renal failure Coagulopathy Liver involvement ARDS Soft tissue necrosis Erythematous macular rash

21. The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000-2004 Data collection from CDC and ABCs Population of 29.7 million persons over 10 US cities San Francisco, Denver, Atlanta, Baltimore, Portland, Albany, Rochester, urban Tennessee, Minnesota, New Mexico, Conneticut January 1, 2000 – December 31, 2004 Invasive GAS = isolation of GAS from a normally sterile site or from a wound specimen obtained from a patient with nec fasc or STSS CID 2007; 45: 853-62

22. 5400 cases of invasive GAS Avg annual incidence = 3.5 cases per 100,000 persons CID 2007; 45: 853-62

23. Clinical Presentation Cutaneous or soft tissue infection (36%) Primary Bacteremia (29%) Pneumonia (15%) GAS isolated from Blood specimens (77%) Joint Fluid (8%) Surgical Specimens (6%) Peritoneal fluid (2%) Pleural fluid (2%) CID 2007; 45: 853-62

26. Case Fatality Rates Overall, CFR was 13.7% Projections of US population estimate that 8950 – 11,500 invasive GAS infections occur annually, with 1050 – 1850 deaths Predictors of Death Increasing Age Residence in Nursing Home Presence of a Specific Disease Syndrome Emm type (1, 3, 12) Underlying condition CID 2007; 45: 853-62

27. Morbidity and Mortality of Patients with Invasive Group A Streptococcal Infections Admitted to the ICU Chart review of all cases of invasive GAS admitted to ICUs in all Ontario, Toronto b/w Jan 1992 and June 2002 62 total patients 64% with skin/soft tissue infections 20% with pneumonia 68% had positive blood cultures 50% with chronic disease Overall mortality 40% Directly correlated with APACHE II scores and with the number of organ failures 55% had STSS: Mortality rate = 68% Chest 2006; 130; 1679-1686

28. Treatment Hemodynamic Support Surgical Therapy Empiric Antibiotics Clindamycin PLUS: A carbapenem OR a PCN plus beta- lactamase inhibitor IVIG (1 gm/kg day one, then 0.5gm/kg days two and three)

29. Limitations in treatment PCN/Beta-lactamase Studies suggest PCN failure with large organsim burden PBPs decrease in the stationary phase of bacterial growth in vitro IVIG Used as an adjunct to antibiotics Able to neutralize superantigens and facilitates opsonization of streptococci Inadequate evidence to support its use

31. Post-Influenza Pneumonia Most common complication of influenza Most frequent in patients with underlying chronic conditions CV or Pulmonary Disease DM, Renal dz, Hemoglobinopathy Immunosuppressed Residents of chronic care facilities Primary Influenza Pneumonia vs. Secondary Bacterial Pneumonia

32. Secondary Bacterial Pneumonia Accounts for ~25% of influenza-associated deaths Influenza causes decrease in size of cells and loss of cilia in epithelium lining the trachea and bronchus S. pneumo most common organism (~48%) S. aureus second most common (19%) H. flu also implicated Typically, a relapse of symptoms after some degree of improvement ? Role of Oseltamivir Curr Med Res Opin. 2007 Dec;23(12):2961-70

33. Have A Great Day!