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What is pneumonia?
Inflammation of lung alveoli resulting in accumulation of exudate and fluid in the lung
What are symptoms are pneumonia?
Cough, chest pain, fever, and difficulty in breathing
Are the alveoli sterile?
What are in the alveoli sacks with pneumonia?
-Pus, dead PMNs
What are host defenses against pneumonia?
- -Mucus: traps microbes (first line defense)
- - Ciliated epithelium: sweeps mucus-trapped microbes towards pharynx out of sinuses and bronchi (1st line defense)
- -Epiglottal reflex: guard against aspiration (gag)
- -Cough Reflex: blasts out bacteria-laden mucus from bronchioles
- -Macrophages: Phagocytise microorganisms that reach the alveoli.
- -Lymphatic Drainage: Flushes phagocytised microbe from bronchioles
What are risk factors: anything that damages the lung tissue?
- -Viral infection or smoking which damage ciliated epithelium of upper airway
- -Fluid accumulation in lung
- -Decreased macrophage action (flu or smoking)
- -Elderly, smokers (50x), miners, having flu, sickle cell anemia
- -Immunosuppressed, chronic cardiovascular disease.
- -Alcohol and drug (aspiration pneumonia)
What does smoking do to the cilia?
-It stops the cilia from working
What kind of organisms cause pneumonia?
What are the gram + bacteria that causes pneumonia?
- Strep pneumoniae
- Staph aureus
What are the gram - bacteria that causes pneumonia?
- Legionella pneumophilae
- Mycoplasma pneumoniae (walking)
- Chlamydia pneumoniae (walking)
- Klebsiella pneumoniae (normal flora, in alcoholics)
What is the acid fast staining bacteria causing pneumonia?
Mycobacterium tuberculosis-TB agent
What percent of pneumonia is caused by strep pneumoniae?
50% of all bacterial causes
What are 2 other common names for strep pneumonia?
- Diplococcus pneumonia
- Pneumococcal pneumonia
What group is pneumococcal according to Lancefield grouping?
Nongroupable, a hemolysis
How will strep pneumoniae appear in the gram stain?
-Frequently join together to form pairs called diplococci
How can strep pneumoniae be distinguished from other streptococci?
-The only a hemolytic strep which is optochin sensitive
What are there 90 specific types of? What is the significance?
- -There are 90 different types of polysaccharide capsules
- -That means you can get it 89 other times
- -Organism trades capsule types by transformation
What are other virulence properties of strep pneumoniae?
- -Capsule: Most important (antiphagocytic)
- -Surface protein adhesions: bind to epithelial cells
- -secretory IgA proteins: disrupts S-IgA mediated clearance
- -Pneumolysin: exotoxin: Destroy ciliated epithelial cells and WBC, suppress phagocytic killing, activate complement pathway resulting in lots of inflammation.
How does the quellung test help epidemiologists?
- -An increase in the opacity and visibility of the capsule of encapsulated organisms resulting from exposure to specific, agglutinating, anti capsular antibodies.
- -Help determine the identity of the new bug in an outbreak in town
- -For stain typing
- -Quellung halo
What are the 3 levels of consolidation might we find in the lung?
- 1. congestion (1-2 days)
- 2. Red hepatization (2-4 days, rusty sputum)
- 3. Gray hepatization (4-6 day)
- Then resolution (8-9th day)
What is congestion?
- -1-2 days
- -Protein-rich edema fluid containing numerous organisms (strep pneumoniae) filling the alveoli. Marked congestion of the capillaries is typical.
What is red hepatization?
- -2-4 days
- -Massive outpouring of PM accompanied by intra-alveolar hemorrhages
- -Many of the red blood cells undergo lysis. These cells, together with PMN, produce the rusty sputum
- -Because the firm consistency of the affected lung is similar to the liver, this stage has been named red hepatization
What is gray hepatization?
- Involves the lysis of PMN and the appearance of macrophages, which phagocytose the fragmented PMN and other inflammatory debris
- -The lung is now no longer congested but still remains firm in this stage.
What is resolution?
- -8-9 days
- -The alveolar exudates is removed and the lung gradually returns to normal
What are 2 ways to recognize involvement of the lung?
- -Chest x-ray, generally localized to lower lobes of lungs (termed lobar pneumonia)
- -Rusty sputum: characteristic of lobar penumococcal pneumonia.
What other diseases are caused by strep pneumonia?
- -Otitis media: primarily in childhood, 80% if all kids get it by 3. Passive smoke exposure, non breast fed infants at higher risk.
- -Sinusitis: occurs in all ages
- -Bacteremia: 85% fatality rate without Rx
- -Meningitis: The leading cause of bacterial meningitis of all ages, 3000/deaths a year,causes the highest post-infection permanent neurological damages
What is the carriage rate of strep pneumoniae?
- -Common inhabitant of the throat and nasopharynx
- -30% of healthy individuals
- -More common in children
- -More in cold seasons
- -Disease occurs when organism spreads to distal loci: Lungs 500,000 cases/yr, Sinuses 7 million/yr, Middle ear 7 million/yr, Meninges 6000/yr
List symptoms and treatment for diplococcal pneumonia?
- -Abrupt onset (contrast to viral and atypical agents)
- -Shaking chills and sustained fever of 39-41 C
- -Pain in chest with deep breath (pleuritic pain)
- -Cough with rusty sputum (blood tinged), represents damage to lungs, generally localized to lower lobes of lungs termed lobar pneumonia
How is treatment of Strep pneumonia changing?
- -Organism is target for many available antibiotics
- -50% of antibiotic prescriptions are for age 0-4 patients for pneumoncoccal otitis media
- -Penicillin has been very effective but rapid changes in resistance lately (Penicillin, cephalosporins, erythromycin, clindamycin, some fluoroquinolones)
- -1998- 25% penicillin resistant, >14% MDR profile, some now only vancomycin sensitive, for meningitis.
What is the 23 valent pneumococcal polysaccharide vaccine (PPV23)?
- -Prevent Strep Pneumonia
- -oldest, introduced in 1987
- -23 serotypes, covers 88% of adult disease-assoicaited strains
- -Purified carb, t-cell independent response
- -Indicated for: >65, HIV, diabetes, splenic dysfunction, high Flu risk, smokers, cardiac/pulmonary disease, complement abnormality
- -Increased in the past two decades 66% have had received PPV
What is the 13 valent pneumococcal conjugate vaccine (PCV)?
- -A vaccine for strep pneumococcal
- -Protein carb (CHO) conjugate
- -Induce a T cell independent response, children < 2years have poor response to CHO, protein component aids a T-cell dependent response, more effective vaccine ages <2, fragment of diphtheria toxin used as protein conjugate.
- -Contains 13 serotypes: these 7 cover > 80% of S. pneumoniae for kids <ages 6, goal to vaccinate all kids under 2
What is the pneumococcal vaccine schedule?
- -4 childhood shots of PCV at (2, 4, 6, 12-15 months)
- -PCV booster or PPV for children older that 2 years old (2-6 years) which are certain high-risk groups
- -Sickle cell anemia, HIV, chronic heart/lung
- -More common among healthy children of certain racial or ethnic groups, such as alaska natives, native americans, and african-americans.
- IPD-Invasive pneumoccoal disease in young children has declined due to vaccine
What is legionella pneumophila?
- -Legionnaires disease acquired its name in 1976 when an outbreak of a pneumonia occurred among people attending a convention of american legion in Philadelphia.
- -200th birthday, many elderly
- -A week later 200 had mysterious pneumonia which killed 34 of them
- -Several months of investigation resulted in identifying the agent as a bacterium that is present in natural moist environment (aquatic saprophyte)
What is the diagnosis of legionella pneumophilia?
- Difficult before: the organism could not be cultured by common culturing techniques, grain stain did not work, it was possible to stain with Fluorescent Antibody stain (FAB)
- Easier today: Sputum is best test. Culture in buffered charcoal yeast extract (BCYE), use FAB
What is the shape of legionella pneumophila?
Gram-negative slender pleomorphic rods
What modes of transmission are we concerned about today with Legionella?
- 10,000-15,000 cases occur each year in US, most sporadically
- Aerosol transmission of Legionella occurs by way of: contaminated cooling towers, evaporative condensers and showers, humidifiers, respiratory therapy equipment, whirlpool spas, decorative fountains.
What are risks factors of legionella?
- Patients with compromised pulmonary functions
- Patients that are immunocompromised: transplant patients, elderly in hospital
- 25% of cases of hospital acquired
- death could occur in 30% of cases
What unusual characteristics do we now know about the biology of this organism?
- -The organism can live in moist environment for a long time: parasitize amoeba in water, survive in biofilms of pipe systems, within human lung macrophage and cause pneumonia
- -Treatable disease with antibiotics but hard to diagnose. of the cases, only 1200-2200 reported, milder form of legionnaires this disease is called pontiac fever.
What are two names for the disease caused by mycoplasma pneumoniae?
- -Primary atypical pneumonia
- -Walking pneumonia
What are biological properties of m. pneumoniae?
- Very small bacterium
- Fastidious (hard to culture), fried egg colony morphology
- -No PG in cell wall (atypical)
- -Sterols in cell wall (atypical)
- -Higher incidence of pneumonia in Military/college population
Why is ampicillin not used to treat walking pneumonia?
- -No PG in wall means no penicillin sensitivity
- -Coccoid or filamentous because no cell wall
How to diagnosis/treatment properties M. pneumoniae?
- Difficult to diagnosis
- based on symptoms, grows slowly in culture 2 weeks
- Chest x-ray: diffused infiltrate not remarkable
- Serological diagnosis: a variety of rapid tests based on indirect hemagglutination of erythrocytes or latex particles coated with M. pneumoniae antigens have been developed and some are commercially available
- PCR: treatment long term with non penicillin family of drugs
What is chlamydia pneumoniae?
- -Gram negative roundish irregular shape
- -ER: elementary body
- -RB: reticulate body
Where does chlamydia pneumoniae grow?
- -Obligate intracellular pathogen that has a unique developmental cycle in mammalian host cells. Cant make own ATP, takes from host.
- - Once inside phagocytic cells of lung (alveolar macrophages), it prevents fusion of phagosome and lysosome
What is the pathogenesis of chlamydia pneumoniae?
- -Respiratory pathogen causes pneumonia, bronchitis, phargngitis, and sinusitis
- -C. pneumonia cause 10% of all community acquired pneumonias
- -Organism can make its way into the walls of various medium and large blood vessels, linger for years inducing the inflammation and immune reaction causing atherosclerosis leading to heart attacks and strokes
What is the treatment of c.pneumoniae?
- Due to the intracellular nature, long term (weeks to months) antimicrobial treatment is needed
- -Macrolides (azithromycin)
What is klebsiella pneumoniae?
- -Encapsulated Gram negative rods found in normal flora of human mouth, skin, intestines
- -Can cause bacterial lobar pneumonia, typically due to aspiration in alcoholics or people with compromised pulmonary function
- -It is also an opportunistic pathogen more commonly causing hospital acquired lung, urinary tract and wound infections
- -New superbug
How many of the pneumonia causing agents do we know?
- only 50% of agent cause pneumonia cases are known.