1. Streptococci & Enterococci David A. Wininger, MD Internal Medicine Residency Program Director Associate Professor, Clinical Internal Medicine Division of Infectious Diseases The Ohio State University Wexner Medical Center 614-293-3989 David.wininger@osumc.edu

2. Learning Objectives  Recognize the structure and microbial physiology of Streptococci and Enterococci and integrate this information with the human pathophysiologic correlates  Define the structure and composition of Streptcocci and Enterococci  Recognize the underlying genetic mechanisms of antibacterial resistance in Streptococci and Enterococci  Describe the nature and mechanisms of action of Streptococcal and Enterococcal virulence factors  Identify the normal human immune response to Streptococcal and Enterococcal infections

3. Learning Objectives  Recognize the epidemiology and ecology of Streptococcal and Enterococcal infections  Describe and differentiate the principles of laboratory diagnosis for Streptococcal and Enterococcal infections  Define the principles of infection prevention for Streptococcal and Enterococcal infections  Recognize treatment options and accurately evaluate their role in the therapy of infections due to Streptococci and Enterococci

4. Streptococci  Catalase negative Gram Stain

5. Classification of Streptococci  Hemolytic pattern  Alpha  Beta  Gamma (On sheep blood agar)  Lancefield Groups: Cell wall carbohydrates by serologic tests  Groups A-H, K-M, O-V  Biochemical properties – see discussion by species Downloaded from: Principles and Practice of Infectious Diseases (on 17 January 2005 06:10 PM)

6. © 2004 Elsevier Group A Streptococci (S. pyogenes) Sheep Blood Agar Plate Beta hemolysis Bacitracin inhibits growth PYR positive

7. Group A Streptococci – Structure & Virulence Factors M-protein Lipoteichoic acid F-protein Capsule

8. Group A Streptococci – Virulence Factors  Toxins  Pyrogenic exotoxins (SpeA, SpeB, SpeC, SpeF) Super-antigens Streptococcal Toxic Shock Syndrome, Scarlet Fever  Enzymes  Streptolysin S  Lyses red blood cells  Streptolysin O  Basis of ASO test  Streptokinases  Lyses clots  DNases  Thins out pus  C5a peptidase  Block chemotaxis

9. Group A Streptococci – Clinical Syndromes Acute Streptococcal Pharyngitis (“Strep Throat”)

10. Group A Streptococci – Clinical Syndromes Strawberry TongueDesquamation (recovery phase) Scarlet Fever (Group A Strep strains producing SPE)

11. Group A Streptococci – Clinical Syndromes ImpetigoErysipelas Cellulitis CDC/Dr. Thomas F. Sellers/Emory University

12. Group A Streptococci – Clinical Syndromes Valvulitis (Mitral valve) Erythema marginatum Rheumatic Fever & Rheumatic Carditis (Non-suppurative, post-streptococcal)

13. Group A Streptococci – Clinical Syndromes Acute Post-Streptococcal Glomerulonephritis (APSGN)

14. Post-Streptococcal Non-Suppurative Complications  Rheumatic Fever  Mostly strep throat M-types  Acute Post-Streptococcal Glomerulonephritis (APSGN)  Some after dermal infection  Rationale for finishing full antibiotic course  Penicillin G works in preventing Rheumatic Fever, BUT NOT APSGN

15. Group B Streptococci (S. agalactiae)  Laboratory Diagnosis: Culture shows a Beta-hemolytic Streptococci expressing “Group B” cell wall carbohydrate. Requires enriched media for optimal growth.  Main Virulence factor: Capsule that prevents phagocytosis  Epidemiology and Ecology: GI & GU tract colonization  Vulnerable populations: Neonates, colonized women post-partum, older patients with cancer or diabetes  Treatment: Easily treated with penicillins (i.e. Penicillin G, Ampicillin)  Cephalosporins or Vancomycin for penicillin-allergic patients

16. Group B Streptococci – Clinical Syndromes  Clinical Disease in Peri-partum Period  Neonatal sepsis (early and late)  Neonatal meningitis  Post-partum sepsis  Prevention of Peri-partum Infections  Pre-partum vaginal screening cultures  Carriers receive antibiotics in labor  Prophylaxis has reduced neonatal sepsis rates  No vaccine is available

17. Group B Streptococci – Clinical Syndromes  Non-pregnant Adults  Urinary tract infections  Bacteremia and sepsis  Soft tissue infections  Musculoskeletal infections  Mainly in patients compromised by: Age Diabetes mellitus Cancer

18. Downloaded from: Principles and Practice of Infectious Diseases (on 17 January 2005 06:09 PM)© 2004 Elsevier Streptococcus pneumoniae Gram Stain  Laboratory Diagnosis  Gram (+) diplococci  “Lancet shaped”  Alpha-hemolytic  Fastidious nutritional req.  Susceptible to optochin  Bile soluble

19. Downloaded from: Principles and Practice of Infectious Diseases (on 17 January 2005 06:11 PM) © 2004 Elsevier S. pneumoniae – Structure & Virulence Factors  Capsule  Key virulence factor  Anti-phagocytic  For sero-typing  Basis for vaccination  Rough strains (avirulent)  Other Virulence Factors  Surface adhesins  Pneumolysin (cytotoxin)  sIgA Protease  Teichoic Acid  H 2 O 2

20. Downloaded from: Principles and Practice of Infectious Diseases (on 17 January 2005 06:09 PM)© 2004 Elsevier S. pneumoniae – Clinical Syndromes Pneumococcal Pneumonia

21. S. pneumoniae – Clinical Syndromes Lung Tissue Acute Left Maxillary Sinusitis No Pneumonia Acute Pneumococcal Pneumonia

22. S. pneumoniae – Clinical Syndromes  Other associated infections  Acute Otitis Media  Acute Bacterial Meningitis  Bacteremia (with pneumonia or meningitis)  Pneumococcal sepsis CDC

23. S. pneumoniae – Treatment & Antibacterial Resistance  Historically highly susceptible to penicillins  Increasing rates of penicillin resistance due to altered penicillin binding proteins (PBPs).  Serious disease  Need susceptibilities to rule out penicillin resistance  Primary empiric treatment usually consists of a 3 rd Generation Cephalosporin (i.e. Ceftriaxone, Cefotaxime)  Alternative treatments include:  Vancomycin  “Respiratory” (anti-pneumococcal) Fluroquinolones (i.e. Moxifloxacin, Levofloxacin)

24. S. Pneumoniae – Normal Human Immune Response & Prevention  Humoral immunity is key  Anticapsular antibodies are protective  Basis for vaccination  Asplenics are at increased risk for serious sepsis!!!  Vaccinate patients prior to elective splenectomy  23-valent vs. 13-valent conjugate vaccine  Acute inflammatory response during disease  Neutrophils

25. Viridans Streptococci  A heterogeneous group (not a single species)  Often alpha hemolytic (“Viridis” – Green)  S. mitior, S. mutans, and numerous others  S. bovis bloodstream infections  occult colon cancer!!  Laboratory Diagnosis  Culture  “Viridans”- grouping is often enough  Speciation  Biochemicals and Mass Spectroscopy  Epidemiology/Ecology  Normal flora or colonizers of oral, GI and GU tracts

26. Viridans streptococci  Clinical Syndromes  Endocarditis, bacteremia, dental abscess and intra-abdominal abscess. (No noteworthy virulence factors)  Normal Human Immune Response/Prevention  Ubiquitous organisms that take advantage of breaks in normal mucosal surfaces, triumphing due to sheer numbers and structural defects of the host (bad teeth, abnormal heart valves, prosthetic materials) but can be cleared with acute inflammation (neutrophils)  Treatment  Often penicillin susceptible, but resistance happens; can add aminoglycoside (for synergy) or use vancomycin while awaiting MIC’s.

27. Enterococci  E. faecalis and E. faecium  Most common pathogenic species  Laboratory Diagnosis  Group D “strep”  Usually alpha hemolytic (can vary!)  Hardy: grows in wide temp range, pH range, salt concentrations, bile salts, aerobic and anaerobic conditions  PYR positive  Catalase negative Gram Stain

28. Enterococci  Ecology and Epidemiology  Fecal flora (GI tract) and can colonize GU tract  Overgrow when antibiotics eliminate other endogenous flora  Spreads patient to patient  Virulence Factors  Adherence and biofilm formation (pili, surface proteins, etc.)  Clinical Syndromes  Urinary Tract Infections  Bacterial endocarditis and other bacteremias  Abdominal wounds and intra-abdominal infections

29. Enterococci – Antibacterial Resistance & Treatment  Inherent resistance to some classes (i.e. cephalosporins)  Intrinsic decreased susceptibility to others (i.e. penicillins)  Multidrug resistance, including to Vancomycin (VRE)  Most commonly seen in E. faecium strains  Treatment depends on susceptibility  Penicillin G or Ampicillin  Vancomycin  Synergy with aminoglycosides (i.e. Gentamicin, Streptomycin)

30. VRE – Mechanism of Resistance

31. Vancomycin Resistant Enterococci (VRE)  Antimicrobial Treatment Options  Linezolid  Daptomycin  Tigecycline  Quinupristin/Dalfopristin  Infection Control Precautions  Minimize antibiotic “pressure”  Contact isolation precautions

32. Summary – Streptococci & Enterococci  Gram positive cocci in pairs or chains  Targeted sites of infection depending on the species  Pathogenesis  merger of the sites of initial contact or colonization and the virulence features of the species  Diagnosis based on Gram stain morphology, hemolysis pattern on Sheep Blood Agar and presence or absence of characteristic cell wall carbohydrates  Penicillin  optimal treatment for a subset of the strep species  Enterococci  Restricted antimicrobial treatment options

34. Thank you for completing this module If you have any questions, write to me at david.wininger@osumc.edu david.wininger@osumc.edu Phone messages can be left at 614-293-3989. David Wininger, MD

35. References  Medical Microbiology, 7 th Ed. Murray, Rosenthal & Pfaller; Chapter 19, pages 188-204; Chapter 20, pages 205-208.

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