Gram Positive Pathogens

1. Gram Positive Pathogens • Staphylococcus • Streptococcus • Enterococcus • Listeria monocytogenes • Bacillus anthracis

2. A ‘coccus’ is a spherical bacteria Staphylococcus tend to cluster in groups While Streptococcus tend to line up in strings

4. Gram-positive bacteria: Staphylococci

5. Staphylococcus aureus Staphylococcus aureus causes a variety of suppurative (pus-forming) infections and toxinoses in humans.

6. Important to distinguish Staphylococcus from Streptococcus • Most Staphylococcus are resistant to Penicillin G • Most produce a -lactamase • Or, may be resistant due to mutation of PBP (as in MRSA) • Most Streptococcus are susceptible to Penicillin G

7. Lipoteichoic Acid also present

9. As is Polysaccharide Capsule

10. Proteins that Disable Our Immune Defenses Include: • Protein A: Binds to IgG • Coagulase: leads to fibrin formation around bacteria, preventing phagocytosis • Hemolysins • Leukocidins • Penicillinase

11. Proteins that Tunnel Through Tissue Include: • Hyaluronidase: breaks down proteoglycans in connective tissue • Staphylokinase: Lyses formed fibrin clots • Lipase: Degrades the fat protective layer on surface of skin • Proease: Destroys tissue proteins

12. Exotoxins Produced Include: • Exfoliatin: causes skin to slough off (scalded skin syndrome) • Enterotoxins: cause food poisoning (vomiting and diarrhea) • Toxic Shock Syndrome Toxin (TSST-1): Causes massive T cell response and outpouring of cytokines, resulting in toxic shock syndrome.

13. 3 Major Pathogenic Types of Staphylococcus: • Staphylococcus aureus • Many types of infections • Staphylococcus epidermidis • Most common cause of infection in indwelling prosthetic devices (prosthetic joints, heart valves, etc.) • Staphylococcus saprophyticus • Leading cause of urinary tract infections in sexually active young women

14. Staphylococcal Scalded Skin Syndrome (SSSS)

15. Staphylococcus causes superficial skin lesions such as boils, styes and furunculosis;

16. Staphylococcus also causes more serious infections such as pneumonia, mastitis (inflammation of mammary gland), phlebitis (inflammation of vein, usually in leg), meningitis (inflammation of meninges), and urinary tract infections;

17. Staphylococcus also causes deep-seated infections, such as osteomyelitis (inflammation of the bone) and endocarditis (inflammation of heart).

18. S. aureus is a major cause of hospital acquired (nosocomial) infection of surgical wounds and infections associated with indwelling medical devices.

19. S. aureus causes food poisoning by releasing enterotoxins into food, and toxic shock syndrome by release of superantigens into the blood stream.

20. Superantigens and TSS • http://highered.mcgraw-hill.com/sites/0072556781/student_view0/chapter32/animation_quiz_4.html Toxic Shock Syndrome can occur via skin, vagina, or pharynx There has been some indication that it was associated with selected materials used in some ultra-abosorbant tampons. These materials are no longer used in the US.

22. Treatment of Infections Caused by Staphylococcus aureus • Antistaphylococcal penicillins: Nafcillin, oxacillin • First Generation cephalosporins: Cefazolin • Second Generation Cephalosporins: Cefuroxime • Third-generation cephalosporins: Ceftriaxone, cefotaxime, ceftizoxime • -Lactam/ -lactamase inhibitor combinations: Ampicillin-sulbactam, piperacillin-tazobactam, ticarcillin-clavulanate • Carbapenems: Imipenem, meropenem

23. Treatment of Infections Caused by Staphylococcus aureus (NOT methicillin resistant)

24. Treatment of Methicillin-resistant Staphylococcus aureus • Vancomycin LINK

25. Treatment of Methicillin-resistant Staphylococcus aureus • Linezolid

26. Treatment of Methicillin-resistant Staphylococcus aureus • Streptogramins (Quinupristin-dalfopristin)

27. Treatment of Methicillin-resistant Staphylococcus aureus • Daptomycin (cubicin)

28. Treatment of Methicillin-resistant Staphylococcus aureus • Tigecycline (Tygacil) Doxycycline

29. Gram-positive pathogens:Streptococcus pneumoniae

30. Types of Streptococci • Group A beta-Hemolytic Streptococci • Streptococcal pharyngitis (Strep throat) • Streptococcal skin infections • Scarlet Fever • Streptococcal toxic shock syndrome • Rheumatic fever • Glomerulonephritis (inflammation of small blood vessels in the kidney)

31. Streptococcus pyogenes

32. Streptococcus pyogenes Impetigo

33. Treatment of Streptococcus pyogenes • Penicillin G • Aminopenicillins: Ampicillin • Aminoglycosides are sometimes added for synergy: Gentamicin +

34. Treatment of Streptococcus pyogenes • Clindamycin is added for severe invasive Streptococcus pyogenes infections + +

35. Treatment for Penicillin-resistant Streptococcus pyogenes (and other penicillin resistant Streptococcus) • Vancomycin • Second-generation cephalosporins: Cefuroxime • Third-generation cephalosporins: cefotaxime, ceftriaxone

36. Necrotizing Fasciitis • Necrotizing fasciitis is a rare condition, also known as flesh-eating bacterial disease, that is usually caused by streptococci, but can also be caused by staphylococci. • The disintegration of the skin tissue is due to the production of toxins, which may result in an overly-zealous response of the immune system.

37. Types of Streptococci (Group B) • Viridans Group Streptococci • Dental Infections • Endocardidis

38. Types of Streptococci (Group D) • Streptococcus pneumoniae S. pneumoniae is a common cause of otitis media (ear infection) and is also a major cause of bacterial pneumonia.

39. Otitis media

40. Streptococcus pneumoniae

41. Treatment of Streptococcus pneumoniae • Penicillin G (high doses) • Aminopenicillins: Ampicillin (high doses) Ampicillin

42. Treatment of Penicillin-resistant Streptococcus pneumoniae • Second Generation Cephalosoporins: Cefuroxime • Third Generation Cephalosporins: Cefotaxime, Ceftriaxone • Quinolones: Moxifloxacin, Levofloxacin • Vancomycin • Macrolides/ketolines: Telithromycin

43. Enterococci

44. Enterococcus Enterococci are gram positive cocci, that are normal residents of the GI tract

45. Two common species are Enterococcus faecalisand Enterococcus faecium. • In order of importance these microorganisms cause the following types of infections • Urinary Tract Infections (UTIs) • Intra - abdominal and intra - pelvic abscesses or postsurgerywound infections • Blood stream infections (BSIs)

46. Enterococcus Resistance Mechanisms

47. Treatment of Infections Caused by Enterococcus • Penicillin G • Aminopenicillins: Ampicillin • Extended-spectrum Penicillins: Piperacillin • Carbapenems: Imipenem, meropenem

48. Treatment of Infections Caused by Enterococcus • For serious infections, add an aminoglycoside for synergy: Gentamicin +

49. Treatment for Infections Caused by Penicillin-resistant Enterococci • Vancomycin

50. Treatment for Vancomycin Resistant Enterococci (VRE) • Linezolid • Tetracycline-like: Tigecycline