NEPAL-2001

1. NEPAL-2001

2. STREPTOCOCCUS • Gram-positive, catalase-negative cocci, part of normal flora in man and animals. A few species cause significant morbidity in man. • Facultative anaerobes. • The "oral streptococci", including the cariogenic Streptococcus mutans, are important members of this group.

3. Gram stain of Streptococcus pyogenes

4. STREPTOCOCCUS - CLASSIFICATION • Clinical presentation (pyogenic, oral, enteric) • Serological properties (Lancefield groups A-H, K-V). • Hemolytic pattern: • ß - wide, clear, translucent zone of complete hemolysis around the colony • a -partial and green (viridans) discoloration • g - no hemolysis. • Biochemical properties

5. STREPTOCOCCUS • Group A Streptococcus(S. pyogenes) (ß-hemolysis) • Group B Streptococcus (GBS) (S. agalacatiae) (ß-hemolysis) • Viridans Streptococci(a-hemolysis) (S. mutans, S. sanguis, S. salivarius, S. mitis, S. anginosus ) • Streptococcus pneumoniae (a-hemolysis) • Enterococcus faecium

6. Group A Streptococcus (S. pyogenes) (ß-hemolysis) (pyo - connected with pus) Suppurative diseases: Pharyngitis - "strep throat" Scarlet fever - a complication of streptococcal pharyngitis Pyoderma (impetigo) - skin infections Erysipelas - acute infection of the skin Flesh-eating disease (invasive fascitis) Streptococcal toxic syndrome (pyrogenic exotoxins) Non-suppurative diseases: Acute rheumatic fever, acute glomerulonephritis

7. Group B Streptococcus (GBS) Streptococcus agalactiae(ß-hemolysis) Septicemia, pneumonia and meningitis in newborn children(neonatal diseases). The major cause of neonatal sepsis in developed countries.

8. Viridans Streptococci(a-hemolysis) (S. mutans, S. sanguis, S. salivarius, S. mitis, S. anginosus ) Dental caries Subacute endocarditis Suppurative intraabdominal infections

9. Streptococcus pneumoniae(a -hemolysis) Pneumonia Sinusitis and otitis media Meningitis Septicemia (bacteremia)

10. Group A Streptococcus (S. pyogenes)Virulence Factors • Capsule - composed of hyaluronic acid identical to that found in connective tissue (non-immunogenic); antiphagocytic. • M protein - the most important virulence factor, located on the end of the hairlike fimbriae, a major antiphagocytic component. • M-like proteins bind the Fc portion of IgG and IgM. • F protein - fibronectin-binding protein (the major adhesin for bacterial attachment to the epithelial cells of the pharynx and the skin).

11. Group A Streptococcus (S. pyogenes)Virulence Factors (cont.) • Pyrogenic exotoxins - erythrogenic toxins - produced by lysogenic strains of streptococci (mediate pyrogenecity [fever], superantigens, responsible for red rash observed in scarlet fever). • Streptolysin S - non-immunogenic cell-bound hemolysin (lyses erythrocytes, leukocytes, platelets; kills phagocytes by autolysis). • Streptolysin O - immunogenic, kills leukocytes by autolysis, used for the ASO test (a recent infection).

12. Group A Streptococcus (S. pyogenes)Virulence Factors (cont.) • Streptokinase (fibrinolysin) - lysing blood clots (fibrin). • DNase - depolymerizes DNA present in pus, reduces the viscosity of pus, facilitates spread of the organisms. • Hyaluronidase ("spreading factor") - degrades connective tissue.

13. Group A Streptococcus (S. pyogenes) - Epidemiology A commensal in the naso/oropharynx of healthy children and young adults, continuous turnover until antibodies to M protein are produced. Spread by airborne droplets and by contact. Disease is caused by recently required strains capable establish an infection before specific antibodies are produced or competitive organisms are able to proliferate.

14. Group A Streptococcus (S. pyogenes) (ß-hemolysis) (pyo - connected with pus) Suppurative diseases: • Pharyngitis - "strep throat" • Scarlet fever - a complication of streptococcal pharyngitis • Pyoderma (impetigo) - skin infections • Erysipelas - acute infection of the skin • Flesh-eating disease (invasive fascitis) • Streptococcal toxic syndrome (pyrogenic exotoxins) Non-suppurative diseases: Acute rheumatic fever, acute glomerulonephritis

15. Acute stage of erysipelas of the leg, acute infection of the skin with Streptococcus pyogenes

16. Group A Streptococcus (S. pyogenes) Treatment • Very sensitive to penicillin (erythromycin for penicillin sensitive patients). • Patients with a history of rheumatic fever - long-term use of antibiotic prophylaxis to prevent recurrent disease. • Antibiotic prophylaxis before the use procedures that induce transient bacteremia (e.g., dental procedure).

17. Group B Streptococcus (S. agalacatiae) Normal flora of the female genital tract in 25-40% of healthy women. A significant cause of septicemia, pneumonia and meningitis in newborn children (neonatal diseases). In ~80% of cases, neonatal infection is acquired during delivery (direct transmission).

18. Group B Streptococcus (S. agalacatiae) Pathogenesis and Immunity • No toxins or virulence factors identified • Antibody developed against the type specific capsular antigens in group B streptococci are protective • Infects neonates lacking antibody (maternal antibodies)

19. Group B Streptococcus (S. agalacatiae) Epidemiology Colonize the lower gastrointestinal tract (GIT) and the genitourinary tract (transient carriage in 10-30% of pregnant women). Infection can occur: • In utero • At the time of birth (80%) • During the first few months of life

20. Group B Streptococcus (S. agalacatiae)Clinical Syndromes • Early-onset neonatal disease (the first 7 days of life): bacteremia, pneumonia, meningitis; 60% of low birth weight, premature infants will die and survivors will have neurological complications (blindness, deafness, severe mental retardation). • Late-onset neonatal disease - from an exogenous source (bacteremia with meningitis, 80% will survive but neurological complications are common). • Infection in pregnant women - urinary tract infections.

21. Group B Streptococcus (S. agalacatiae)Treatment Penicillin G is the drug of choice, but the minimum inhibitory concentration (MIC) is approx. 10 X greater than with group A streptococci (S. pyogenes). Tolerance to penicillin - penicillin + aminoglycoside. Resistance to erthromycin and tetracycline has been observed. In the U.S. S. agalacatiae causes ~2500 cases of infection and 100 deaths per year among newborns.

22. Viridans Streptococci (S. mutans, S. sanguis, S. salivarius, S. mitis, S. anginosus ) Heterogeneous group of a-and non-hemolytic - isolated from the oropharynx the gastrointestinal tract (GIT) the urogenital tract Associated with dental caries, subacute endocarditis (60%), and suppurative intraabdominal infections Vertically transmitted from mother to child

23. Streptococcus pneumoniae (pneumococcus) An encapsulated Gram-positive cocci, oval or lancet-shaped, arranged in pairs (diplococci) or short chains a-hemolytic colonies

24. Gram stain of Streptococcus pneumoniae

25. Streptococcus pneumoniaePathogenesis and Immunity • Capsule- needed for virulence, inhibits phagocytosis in the absence of specific antibodies; non-encapsulated [rough] strains are avirulent • Protein adhesin • Secretory IgA protease • Pneumolysin • Teichoic acid • Hydrogen peroxide

26. Streptococcus pneumoniaeEpidemiology • S. pneumoniae - a commensal in the throat and nasopharynx of healthy individuals (5 to 75%). • Transmission via respiratory droplets. • Spread from the nasopharynx and oropharynx to distal loci: lungs (pneumonia), paranasal sinuses (sinusitis), ears (otitis media), and meninges (meningitis).

27. S. pneumoniae - Clinical syndromes • Pneumonia - aspiration of the endogenous oral organism (lobar pneumonia). • Sinusitis and otitis media - usually preceded by a viral infection of the upper respiratory tract. Otitis usually in children. 3. Meningitis - spread into CNS, primarily a pediatric disease but can occur at all ages. About 15% of meningitis in children and 30-50% of adult disease is caused by S. pneumoniae. 4. Septicemia (bacteremia) - 25-30% of patients with pneumococcal pneumonia and > 80% of patients with meningitis.

28. S. pneumoniae the most common bacterial cause of Pneumonia Meningitis Children’s ear infections

29. S. pneumoniae - Treatment • Penicillin is the drug of choice. • Penicillin resistant strains developed in 1977 and now 1/3 of all cases in the U.S. are penicillin resistant (a decreased affinity of penicillin for the penicillin-binding proteins present in bacterial wall). • Vaccine available (covers most pathogens and is long lasting) but still does not cover those especially at risk pneumococcal disease (e.g., renal transplants, young children, and the elderly).

30. Pneumococcal conjugate vaccine (PCV7) • Approved for infants and toddlers. • Protection for at least 3 years so children vaccinated • as infants will be protected when they are at greatest risk • for serious disease. • Who should get the vaccine and when? • Children under 2 years of age • The routine schedule for pneumococcal conjugate vaccine • is 4 doses, one dose at each of these ages: • ~  2 months                ~  6 months • ~  4 months               ~ 12 months • (See lecture notes!)

31. Gram stain of Enterococcus faecalis

32. ENTEROCOCCUS • Members of the GI tract - one of the most feared nosocomial pathogens !!!!!!!! • Many strains are completely resistant to ALL conventional antibiotics • VREF - vancomycin-resistant Enterococcus faecium emerged in 1989 • By 1997 according to CDC, 50% of all E. faecium were VREF • Zyvox (linezolid) and Synercid - approved for the treatment of VREF bacteremia

33. High Sierra - Sabrina Lake