Chapter 16 and 17 - part 2

beta

hemolysis type for streptococcus pyogenes

beta

hemolysis type for streptococcus agalactiae

beta

hemolysis type for streptococcus dysgalactiae

alpha, beta or gamma

hemolysis type for enterococcus faecalis and enterococcus faecilum

alpha

hemolysis type for streptococcus pneumoniae

Spherical cocci, 1–2 µm in diameter.

What is the shape and size of Streptococcus pyogenes?

Short chains in clinical specimens; longer chains in liquid media

How does S. pyogenes appear in clinical specimens vs. liquid media?

Enriched blood agar.

What is the optimal medium for S. pyogenes growth?

High glucose concentrations

What inhibits S. pyogenes growth in culture media?

1–2 mm white colonies with large zones of β-hemolysis.

What are the colony characteristics of S. pyogenes on blood agar after 24 hours?

Streptococcus pyogenes

What is the most common bacterial cause of pharyngitis?

"Flesh-eating bacteria" (causes life-threatening myonecrosis)

What is the nickname for S. pyogenes when it causes severe tissue infections?

M protein

what is the virulence factor? S. pyogenes

• Encoded by the gene emm

• Resists phagocytosis and plays a role in adherence to mucosa •Blocks C3b binding

Hyaluronic Acid Capsule

what is the virulence factor? S. pyogenes

• Weakly immunogenic

• Prevents opsonized phagocytosis by neutrophils

macrophages

• allows masking of antigens

C5a peptidase

what is the virulence factor? S. pyogenes

A serine protease that inactivates C5a

protein F (fibronectin binding protein)

what is the virulence factor? S. pyogenes

• Adhesion molecules that mediate attachment to host epithelial cells

• Secures attachment of streptococci to mucosal cells

Streptococcal pyogenic exotoxins

• originally called erythrogenic toxins

• produced by lysogenic strains ofstreptococci

• Four immunologically distinct heat-labile (SpeA, SpeB, SpeC, and SpeF)

• Responsible for clinical manifestation on severe

streptococcal diseases (necrotizing fasciitis, streptococcal toxic shock syndrome)

Streptolysin S (Serum-stable)

Oxygen-stable, nonimmunogenic cell-bound hemolysin

Produced in the presence of serum

Seen around colonies incubated aerobically

Stimulates release of lysosomal contents after engulfment

Responsible for the Beta-hemolysis seen in BA

streptomycin O

Oxygen-labile, highly immunogenic

responsible for the hemolysis on BA plates incubated anaerobically

• Antibodies readily form against Streptolysin O

• ASO antibodies useful for documenting group A streptococcal infections

Irreversibly inhibited by cholesterol in skin lipids

Streptokinase A&B

• Mediate cleavage of plasminogen, releasing protease plasmin that cleaves fibrin and fibrinogen

• Can lyse blood clots and fibrin deposits and facilitate rapid spread of s. pyogenes in infected tissues

• Anti-streptokinase antibodies - useful markers for infections

Via respiratory droplets.

How is S. pyogenes spread from person to person?

soft-tissue infections

preceded by initial skin colonization of S. pyogenes then introduced into superficial or deep tissues through break in skin.

Bacterial Pharyngitis

The most common clinical manifestations of GAS

infections are pharyngitis and tonsilitis

• reddened pharynx with exudates generally present, cervical lymphadenopathy can be prominent

• Incubation Period: 1 - 4 days • Characterized by:

• Sore throat, Malaise, Fever and Headache

• Nausea, Vomiting and Abdominal pain (not usual) • Inflamed tonsils and pharynx

• Swollen lymph nodes

scarlet fever

• Diffuse erythematous rash beginning on the chest and spreading to the extremities

• Rash disappears over the next 5-7 days and is

followed by desquamation

• Complication of streptococcal pharyngitis

pyoderma

Localized skin infection with vesicles progressing to pustules; no evidence of systemic disease

erysipelas

• Rare Localized skin infection with pain, inflammation, lymph node enlargement, and systemic symptoms

• Observed frequently in elders

cellulitis

• Infection of the skin that involves the subcutaneous tissue

• May lead to gangrene in patients with peripheral

vascular disease or diabetes

Necrotizing Fasciitis

• Deep infection of the skin that involves destruction of

muscles and fat lavers

• Characterized by rapidly progressing inflammation and necrosis of the skin

Streptococcal Toxic Shock Syndrome

Multiorgan svstemic infection resembling staphylococcal toxic shock syndrome; however, most patients are bacteremic and has evidence of fasciitis

rheumatic fever

• Characterized by inflammatory changes of the heart (pancarditis - rare condition with poor prognosis combining endocarditis, myocarditis with abscess

formation, and purulent pericarditis), joints (arthralgias to arthritis), blood vessels, and subcutaneous tissues

Typically follows S. pyogenes pharyngitis

Acute glomerulonephritis

Acute inflammation of the renal glomeruli with edema, hypertension, hematuria, and proteinuria

penicillin

S. pyogenes is sensitive to

Oral penicillin V or amoxicillin

What is the first-line treatment for streptococcal pharyngitis?

An oral cephalosporin or a macrolide

What is used to treat streptococcal pharyngitis in penicillin-allergic patients?

Intravenous penicillin combined with a protein synthesis-inhibiting antibiotic (e.g., clindamycin).

What is the recommended treatment for severe systemic S. pyogenes infections?

Requires drainage and aggressive surgical debridement in addition to antibiotics

How are serious soft-tissue infections managed?

S. aglalactiae

• Only streptococci with group Bantigen.

• First recognized as cause of puerperal sepsis.

• Important cause of septicemia, pneumonia, and meningitis in newborn children

• 0.6-1.2 um, form short chains in clinical specimensand longer chains in culture.

• Colonies are large with narrow zone of B-hemolysis.

Group-specific cell wall polysaccharide (Group B antigen), Nine type-specific capsular polysaccharides (la, lb, and Il to VIII), and Surface proteins (most common: c antigen)

3 Serologic Markers Used to Classify GBS

Serotypes la, Il and V

most commonly associated with colonization and disease

Polysaccharide Capsule

• Most important virulence factor of S. agalactiae

• Prevents phagocytosis but is ineffective after opsonization

• Interferes with phagocytosis until patient develops type-specific antibodies

Sialic Acid

• Most important component of the capsule and critical virulence determinant • present in type la, lb, and I.

• Inhibits activation of alternative complement pathway, interfering with

phagocytosis.

The lower gastrointestinal tract and genitourinary tract

Where does S. agalactiae commonly colonize in the human body?

Premature delivery, Premature rupture of membranes, and Intrapartum fever

Name three maternal risk factors that increase the chance of neonatal GBS transmission.

Ia, III, and V

What GBS serotypes are most commonly involved in early-onset disease?

III

What GBS serotypes are most commonly involved in late -onset disease?

Ia and V

Which serotypes are most common in GBS disease in adults?

Early - onset neonatal disease

• Occurs less than 7days after birth, infected newborns develop signs and symptoms of pneumonia and sepsis

• Most infections of infants occur in the frst 3 days after birth, usually within 24 hours. This infection is commonly associated with obstetric complications, prolonged rupture of membranes, and premature birth

• The mortality rate in GBS-infected infants is high, and death usually occurs fi treatment is not started quickly

Late - onset neonatal disease

• Occurs between 1 week and 3 months after birth, neonates develop signs and symptoms of bacteremia with meningitis

• The organism is rarely found in the mother's vagina before birth

• The mortality rate is considerably less than the mortality rate associated with early-

onset disease, but ti is high enough to be of serious concern.

infections in pregnant women

• Most often present as postpartum endometritis, wound

infections, and urinary tract infections

• Bacteremia and disseminated complication mav occur

infections in other adult patients

Most common diseases include bacteremia. pneumonia, bone and joint infections, and skin and soft-tissue infections

S. pneumoniae

• Isolated independently by Pasteur and Steinberg more than 100 years ago.

• Encapsulated gram-positive coccus, 0.5-1.2 pm in diameter, oval, and arranged in pairs (diplococci) or short chains.

• Colonial morphology:

• Encapsulated strains: large (1-3 mm diameter on BAP), smaller on chocolate 9

agar, round and mucoid

• Nonencapsulated strains: smaller and flat

• Colonies undergo autolysis with aging - central portion dissolves leaving a dimpled appearance.

S. pneumoniae

• Appear a-hemolytic fi incubated aerobically, B-hemolytic fi grown anaerobically.

• Fastidious nutritional requirements, only grows on enriched media supplemented with blood products.

• Can ferment carbohydrates, producing lactic acid as primary metabolic by- product.

• Grows poorly in media with high glucose concentrations because lactic acid rapidly reaches toxic levels.

• Complex polvsaccharide capsule - covers virulent strain.

• Used for serologic classification of strains, current more than 90 strains.

hydrogen peroxide

Production of __ can also lead to tissue damage caused by reactive oxygen intermediates.

Phosphorylcholine

can bind to receptors for platelet-activating factor expressed on surface of endothelial cells, leukocytes, platelets, and tissue cells (i.e., lungs and meninges).

receptors

Binding to __ allows bacteria to enter the cells, protecting them from opsonization and phagocytosis, and pass into sequestered areas (i.e., blood and CNS).

Where does S. pneumoniae commonly live in healthy individuals?

throat and nasopharynx

Around 6 months of age

At what age does pneumococcal colonization typically begin? S. pneumoniae

During cool months

When is pneumococcal carriage and disease most common? (S. pneumoniae)

Pneumococcal Pneumonia

• Acute onset with severe chills and sustained

fever; productive cough with blood-tinged sputum; lobar consolidation

• A result of disturbance of the normal defense barriers

• For an individual to contract _, the organism must be present in the nasopharynx, and the individual must be deficient

in the specific circulating antibody against the capsular type of the colonizing strain of S. pneumoniae.

Meningitis

• Severe infection involving the meninges, with headache, fever, and sepsis

• High mortality rate and severe neurologic defects in survivors

Bacteremia

• More common in patients with meningitis than with

pneumonia, otitis media, or sinusitis

• Overwhelming sepsis in asplenic patients

Penicillin

What was historically the drug of choice for S. pneumoniae?

Vancomycin + Ceftriaxone

What is the recommended empirical treatment for S. pneumoniae?

Neisseria

• Aerobic, nonmotile, non-spore forming Gram (-) diplococci

• 0.6 to 1.0 um in diameter; coffee- bean shaped diplococci

• Usually intracellular

• Cytochrome oxidase (+) and Catalase (+)

• Many Are capnophilic, requiring carbon dioxide for growth, and have optimal growth in a humid atmosphere

• Habitat: Inhabits the mucous membranes of respiratory and urogenital tracts

culture media

Pathogenic and nonpathogenic species can be differentiated through growth on

_ : (neisseria spp)

Nonpathogenic strains

grows on both blood agar and nutrient agar

N. meningitidis

grows on blood agar and variably on nutrient agar

N. gonorrhoeae

do not grow on both media

neisseria

Only grows on enriched chocolate agar and other supplemented media

• Require cystine and energy source (e.g., glucose, pyruvate, lactate), and other

supplements (i.e., amino acids, purines, pyrimidines, vitamins)

• Grows best in 35 °C to 37 °C, with humid atmosphere supplemented with 5%

carbon dioxide.

N. meningitidis

Which Neisseria species has a capsule that contributes to virulence?

Pili (fimbriae)

What structure aids in attachment to host cells in Neisseria spp.?

Receptors for human transferrin

What do Neisseria species use to acquire iron in the host?

Lipooligosaccharide (LOS) or Endotoxin

lipid Amoiety and core LOS of

lower-molecular-weight that differentiates it from the lipopolysaccharide found in most gram-negative bacilli and is loosely attached to the underlying peptidoglycan

IgA protease, which cleaves secretory IgA

What enzyme do Neisseria species use to evade immune defenses on mucosal surfaces?

Neisseria gonorrhoeae

• Intracellular pathogens found predominantly within PMNs.

• Best grown in Thayer Martin agar (chocolate agar +antibiotics that inhibit

growth of other organisms).

• Colonies: small, curved, translucent, non-pigmented, non-haemolytic, and

19 emulsifiable.

Neisseria gonorrhoeae

• Commonly called gonococci

• has no true carbohydrate capsule but has a capsule-like negative charge

pili (fimbrae)

hair--like appendages used for attachment of organism to host cells. Made of pilin protein - contains hydrophobic amino acids, enhancing attachment and resistance to phagocytosis

OPA proteins

• Outer membrane proteins.

• Help to facilitate interaction with host cells

• Acts as receptors for host cells facilitating bacterial attachment, incursion, response.

• 3-4 antigenically variable types present on outer layer

• POR (Porin Protein P ||)

POR (Porin Protein P II)

• Located on cell membrane.

• Responsible for penetration and intracellular attack on human cells

• 2-3 antigenically variable types present on outer membrane

Rmp (Protein lI)

• Reduction- modifiable protein.

• An outer-membrane protein that complexes with POR, OPA, and lipooligosaccharide (LOS).

• Serves to block antibodies produced against the organism

Lipooligosaccharide (LOS)

Responsible for toxic effects seen in gonococcal infections

• Secretes 2enzymes: Protease and Phospholipase, mediating the mucosal

damage of host tissues

• Structurally resembles glycosphingolipids ni the human cell membrane, masking the organism from immune response of host cells

• Other proteins - Lip (H8), Fbp (ferric-binding protein), IgA1 protease

Protease and Phospholipase

Lipooligosaccharide (LOS): Secretes 2 enzymes: __, mediating the mucosal damage of host tissues

Gonorrhea

Purulent discharge for involved site (ex. Urethra, cervix, epididymis, prostate, rectum) after 2-5-day incubation period

men

symptoms for?
• Acute Urethritis, usually resulting in purulent discharge and dysuria (painful urination), are the most common manifestations.

• Asymptomatic gonococcal infections ni men are uncommon

• Complications in male patients include ascending infections such as prostatis and epididymis

female

symptoms for?

Symptoms include dysuria, cervical discharge, and lower abdominal pain

• 50% of cases in women may be asymptomatic

o Complications include pelvic inflammatory disease (which may cause

sterility), ectopic pregnancy, or perihepatitis (Fitz-High-Curtis syndrome)

disseminated infections

Spread of infection from genitourinary tract through blood to skin or joints characterized by pustular rash with erythematous base and suppurative arthritis in involved joints

• Blood-borne dissemination of N. gonorrhoeae occurs in less than 1% of all infections

ophthalmia neonatorum

• A gonococcal eye infection, during vaginal delivery through an infected birth canal.

• Can result in blindness fi not treated immediately

• Ocular infections can occur in adults because of inoculation of the eye with

infected genital secretions or as a result of laboratory accidents.

Ceftriaxone plus Azithromycin

What is the current treatment of choice for Neisseria gonorrhoeae?

N1% silver nitrate eye drops as prophylaxis.

What is used to prevent ophthalmia neonatorum in newborns?

Neisseria meningitidis

• Only found in humans but can be found as a commensal as well as an invasive pathogen

• Found in the upper respiratory tract in humans.

• Share 70% DNA homology with N. gonorrhoeae. Can be differentiated by

presence of polysaccharide capsule (absent in N. gonorrhoeae). • Oxidize glucose and maltose by producing acid but nogas.

• Commonly called meningococci.

Capsular Polysaccharide

virulence factor of Neisseria meningitidis: acts as antigen, found in circulation during infection

Pili

virulence factor of Neisseria meningitidis: enhance attachment and evade phagocytosis

Cytolytic enzyme

virulence factor of Neisseria meningitidis: major virulence causing mediator

POR & OPA proteins

virulence factor of Neisseria meningitidis: resemble that of gonococci and share similar pathogenesis pattern caused in host

Neisseria meningitidis

• Can be found on the mucosal surfaces of the nasopharynx and oropharynx in 30% of the population.

• The organism is transmitted by close contact with respiratory droplet secretions from a carrier to a new host.

• Only a few newly colonized hosts develop meningococcal disease, with the highest incidence being found in infants and adolescents.

• Highest incidence of disease occurs ni children younger than 1 year old, institutionalized people, and patients with late complement deficiencies.

Neisseria meningitidis

• Of the 12 meningococcal encapsulated serogroups, A, B, C, Y, and W-135 account for most cases of disease in the world

• Pneumonia most commonly caused by serogroups Yand W135

o Diseases in underdeveloped countries are associated with serogroups A and W135

• Disease occurs worldwide, most commonly in dry, cold months of the year.

Fulminant Meningococcemia (Sepsis)

May occur with or without meningitis and carries 25% mortality rate, even fi treated.

Disseminated infection characterized by thrombosis of small blood vessels and •

multiorgan involvement; small petechial skin lesions coalesce lesions into larger hemorrhagic

Meningitis

Purulent inflammation of meninges associated with

headache, meningeal signs and fever; high mortality rate unless promptly treated with effective antibiotics

Pneumonia

Milder form of meningococcal disease characterized by bronchopneumonia in patients with underlying pulmonary disease

Ceftriaxone or Cefotaxime

What is the initial treatment for suspected meningococcal disease?