1. Case Study Pathogenic Bacteriology 2009 Case #64 Hien Dang Note: Embedded in your PowerPoint, you must address all questions in the case!

2. Case Summary  30-year-old male exposed to chicken pox  Fluid filled lesions on upper trunk –Chicken pox caused skin lesions that opened up the following week, crusted over, and healed  allowed pathogen to enter  Septic Shock  Unresponsive to antibiotics, treated with vancomysin, Cardiopulmonary arrest.  Death.

3. Key Information Pointing to Diagnosis  3 weeks prior to admission: –Exposure to daughter infected with chicken pox  Treated with acyclovir  8 days prior to admission: –Developed abdominal pain –Fluid filled lesions that opened up, crusted over, healed –Large, red Vesicle appeared on buttock  Treated with hydrocortisone cream  1 day prior to admission: –Shortness of breath, pain and swelling in leg, vomiting  Admission to local hospital: –Treated with antibiotics –Low Respiratory rate, decreased systolic blood pressure –Unresponsive and Intubated

4. The Diagnosis for Case #  Admission to a new hospital –Treated with Acyclovir and Vancomysin  Lab Results: –Liver failure, kidney failure, muscle breakdown  Operating Room: –Gross purulence in calf towards tracking up to thigh –Ischemic dead muscle with viable muscle tissue in thigh  Post Surgery: –Cardiopulmonary arrest –Could not be resuscitated

5. Classification Gram Stain Results, and Microscopic Appearance  Family: Streptococcaceae  Genus: Streptococcus  Species: pyogenes –Gram (+) –Cocci arranged in chains –Carbohydrate Capsule –Facultative anaerobe  Pathogen identified as Streptococcus pyogenes

6. Streptococcus pyogenes Diseases and Pathogenesis  Pharyngitis  Wound Infections  Erysipelas  Scarlet Fever

7. Streptococcus pyogenes Diseases and Pathogenesis  Acute glomerulonephritis  Rheumatic Fever  Necrotizing fasciitis

8. Streptococcus pyogenes Pathogenesis  Virulence factors: –Capsule  Hyaluronidase –M protein  Major virulence factor, protects S. pyogenes from opsonization and phagocytosis  Adherence  Superantigen, causes shock in the affected patient –Patient experienced liver and kidney failure, fever, and Sepsis

9. Streptococcus pyogenes Pathogenesis  Virulence Factors –Erythrogenic Toxins  Produces a toxic shock like syndrome similar to that caused by Staphylococcus aureus  Superantigen: –Superantigen causes non-specific stimulation of T cells, rendering the immune response useless. –Scarlet Fever is associated with superantigen production. –DNAse –Streptolysin S –Streptolysin O

10. Diagnosis/Isolation/Identification/ of Pathogen X  Media –Sheep Blood Agar at 37°C  With Bacitracin antibiotic disk  Biochemical Testing –β-Hemolysis –Catalase (-) –Oxidase (-) –SXT Resistant –Taxo A Sensitive (susceptible to Bacitracin)

11. Therapy, Prevention and Prognosis  Antimicrobial Therapy: –Penicillin –Erythromycin (if allergic to Penicillin) –Hydrocortisone cream is NOT effective  Applied at red vesicle, alleviated symptoms, but did not directly treat the bacteria, allowed it to remain  Vaccine: –Difficult to develop, poorly immunogenic –Antibodies are protective against a specific type of M protein

12. Primary Research Article Contributing to the Understanding of the Disease caused by Streptococcus pyogenes  O’Loughlin, RE, Roberson, A, et al. 2007. The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000-2004, Clinical Infectious Diseases 2007;45:853–862.  Purpose: –To estimate the potential impact of a multivalent GAS vaccine.  Methods: –Collected data from Jan 2000 to Dec 2004 via CDC at 10 US sites. –Invasive GAS disease determined from patient with necrotizing fasciitis or streptococcal toxic shock syndrome. –All isolates were emm typed. –Used US census data to calculate rates and to make age and race-adjusted national projections.

13. Primary Research Article Contributing to the Understanding of the Disease caused by Streptococcus pyogenes  Results: –Development of GAS vaccine is challenging because of the vast number of emm types (>100) –Also difficult due to potential cross-reactivity between epitopes in the organism’s M protein and human tissue  Conclusion: –Introducing a vaccine could significantly reduce morbidity significantly reduce morbidity and mortality and mortality  This supports my case that a vaccine is difficult to develop. a vaccine is difficult to develop.

14. Take Home Message  Sepsis  Septic Shock  Typical symptoms –Pus formation –Liver failure –Kidney failure  Pathogen –Streptococcus pyogenes  Diagnostics –Antimicrobial testing involving Bacitracin –Hemolysis test (Beta-hemolytic)  Therapy –based on Penicillin treatment for ten days immediately following infection.  Prevention –Maintain proper hygiene to avoid mild superficial skin infections –Ensure that open wounds heal properly without contact with unsanitary or infectious persons

15. References  O’Loughlin, RE, Roberson, A, et al. 2007. The Epidemiology of Invasive Group A Streptococcal Infection and Potential Vaccine Implications: United States, 2000-2004, Clinical Infectious Diseases 2007;45:853–862.  McQueen, Nancy. 2009. Streptococcus Lecture. California State University Los Angeles.  Smoot, LM, McCormick JK, et al. 2002. Characterization of Two novel pyrogenic toxin superantigens made by an acute rheumatic fever clone of Streptococcus pyogenes associated with multiple disease outbreaks. Infection and Immunity, 70:7095-7104.  Norrby-Teglund, A, Thulin, P, et al. 2001. Evidence for superantigen involvement in severe group A streptococcal tissue infections. Jour Infec. Disease 184:853-60.