4 Bacterial PNA 1 & 2 Flashcards
Pneumonia is defined as …
Inflammation of the lung and parenchyma, including the alveoli, respiratory bronchioles, etc
PNA with involvement of the entire lobe
Lobar pneumonia
Bronchopneumonia is just the bronchi?
PNA is usually due to an infectious agent, such as…
BACTERIA
Fungi
Viruses
Parasites
6th leading cause of death in the US
PNA - most common infectious cause of death
How does mortality rate from PNA different in outpatient vs inpatient settings?
1% in outpatient
Up to 25% in infections requiring hospital admission
The two major categories of PNA
Hospital acquired (nosocomial) - develops within 72 hours of admission
Community acquired (CAP)
Community acquired PNA is further subdivided into what two categories?
Typical (usually Strep pneumo, H flu, K pneumo, or Staph aureus)
Atypical (usually Zoonotic, nonzoonotic, or with extrapulmonary involvement)
3 zoonotic pathogens that cause atypical PNA
Chlamydia psittaci (psittacosis) Francisella tularensis (tularemia) Coli Ella burnetii (Q fever)
3 non-zoonotic pathogens that cause atypical PNA
Chlamydia pneumoniae
Mycoplasma pneumoniae
Legionella pneumoniae
Atypical PNA is usually unresponsive to …
ß-lactams
Also, difficult to diagnose
Typical or Atypical PNA: Sudden onset
Typical
Typical or Atypical PNA: Gradual onset
Atypical
Typical or Atypical PNA: Sick appearing, high fever (>103)
Typical
Typical or Atypical PNA: Well appearing, lower fever (<103)
Atypical
Typical or Atypical PNA: Chills/shaking
Typical
Typical or Atypical PNA: Productive cough
Typical
Typical or Atypical PNA: Non-productive cough
Atypical
Typical or Atypical PNA: Pleurisy
Typical
Typical or Atypical PNA: Consolidation (well-defined infiltrates)
Typical
Typical or Atypical PNA: Patchy, ill-defined infiltrates
Atypical
Typical or Atypical PNA: Chest pain, SOB
Typical
Typical or Atypical PNA: Body aches, diarrhea, abdominal pain
Atypical
Gram-positive, lancet-shaped diplococcus
Streptococcus pneumoniae
Alpha-hemolytic colonies
Streptococcus pneumoniae
Green colonies on blood agar
Streptococcus pneumoniae
Optochin sensitivity
Streptococcus pneumoniae
Encapsulated strains are virulent
Streptococcus pneumoniae
_________ increase the risk of pneumococcal pneumonia
Viral infections (more common in colder, wetter months)
The major reservoir of Streptococcus pneumoniae infections
Asymptomatic carriers (because it’s an irregular normal flora component)
Major virulence factor for Streptococcus pneumoniae
Capsule
Basis for serotyping (90 serotypes) and the basis for anti-pneumococcal vaccines
Inhibits phagocytosis by interfering with complement activity and preventing C3b opsonization
Other protective virulence factors for Streptococcus pneumoniae besides the capsule
IgA Protease - degrades host secretory IgA
Hydrogen peroxide —> apoptosis in host cells and elimination of competing bacteria
Other binding virulence factors for Streptococcus pneumoniae
Pili - contributes to the colonization of the upper respitatory tract and activates production of large quantities of TNF
Surface Proteins - Choline binding proteins (Adhesins that interact with the carbs on the surface of pulmonary epithelial cells)
What is the Peptidoglycan-teichoic acid complex?
A Streptococcus pneumoniae virulence factor that illicit a significant immune response and acts as a potent immunomodulator
What is Pneumolysin?
Another Streptococcus pneumoniae virulence factor
Interacts with target cell membrane to form transmembrane pores —> cell lysis and activation of complement
What is Autolysin
Another Streptococcus pneumoniae virulence factor that causes lysis of pneumococcus and results in the release of pneumolysin
Released in response to antibiotic therapy and stationary phase
Is an attempt by the organism to dampen host immune response
What is the pathogenesis of a Streptococcus pneumoniae infection?
Pneumococcus enters respiratory tract through aspiration
Multiplies in tissue (stimulates immune response to cellular components)
Multiplication results in disease from heightened immune response
PNA develops, possibility for hematogenous spread via lymphatic drainage in lungs
Fibrinous edema fluid in alveoli —> red cells and leukocytes —> tissue consolidation
Resolution occurs with the absorption of fluid and phagocytosis of remaining cells
Clinical manifestations of Streptococcus pneumoniae infection
Sudden onset of fever
Chills
Chest pain
Productive cough with purulent RUST COLORED sputum
Bacteremia
CXR shows consolidation in lungs
Confirmed by presence of gram-positive diplococci on sputum
Special tests to confirm Streptococcus pneumoniae and rule out others
Optochin sensitivity
Bile solubility (bile will lyse Streptococcus pneumoniae but no effecton other alpha-hemolytic strep)
Quelling reaction to observe capsules
Agglutination tests for capsular polysaccharides
Genetic probe test
DOC for Streptococcus pneumoniae infection
Penicillin G used in empiric therapy - but resistance is becoming common
What is the difference between the two pneumococcal vaccines?
23-valent capsular polysaccharide represents 85-90% of the infections in US - recommended for persons >65 or other predisposing factors
13-valent capsular polysaccharide covers >80% of infections in children 6 years and younger, conjugated to a carrier protein
Non-motile, gram-negative bacillus coated by a thick slimy capsule
Klebsiella pneumoniae
Can cause both typical CAP and NP
Klebsiella pneumoniae is more common in what populations?
Alcoholics and DM
Often seen in the homeless population
Primary virulence factor for Klebsiella pneumoniae
Polysaccharide capsule (antiphagocytic, prevents MAC-mediated lysis)
Also ADHESINS (either fimbrial or non-fimbrial)
Aggressive necrotizing CAP with predilection for the upper lobes, causing severe illness with rapid onset high fever
Klebsiella pneumoniae
Patients will often have productive cough with a thick, blood tinged sputum (Currant jelly sputum)
Often fatal, even with abx treatment
Diagnosing Klebsiella pneumoniae
Gram stain/cuture showing mucous capsule
Presence of currant jelly sputum
Cavitation on CXR
Treatment of Klebsiella pneumoniae
Empiric therapy used due to rapid progression of disease
Susceptibility testing required as it is ß-lactamase producing
Combo treatments with:
• Aminoglycosides
• 3rd gen cephalosporins
• Fluoroquinolones
Non-motile, gram-negative coccobacillus that can be either encapsulated or non-encapsulated
Haemophilus influenzae
Has ability to lose its capsule (non-typeable H. influenzae) but is still capable of causing disease
Contains lipooligosaccharide in cell wall
Haemophilus influenzae
Functions as a virulence factor similar to LPS
Colonies of this bacterium require factors from RBCs for growth but do not have hemolytic properties
Haemophilus influenzae
Most strains of Haemophilus influenzae are classified as …
Opportunistic pathogens
Nontypeable Haemophilus influenzae is part of the normal flora in ~80% of the population
Type B of this bacterium can cause pneumonia in infants and young children
Haemophilus influenzae
Causes 2-4% of Haemophilus influenzae-related pneumonia’s
Haemophilus influenzae virulence factors
Polyribosylribitol phosphate (PRP) capsule*** (renders it resistant to phagocytosis by PMNs
Neuraminidase
IgA protease
Fimbriae (required for successful colonization in the nasopharynx
LOS
Satellite growths on blood agar
Haemophilus influenzae
Only possible in co-infections
Colonies of Haemophilus influenzae will appear as convex smooth, pale, grey or transparent colonies
Test to detect Haemophilus influenzae other than culture
ID-Latex Particle Agglutination test (LAT)
Easier to achieve definitive results than other culture methods
Relies on antigen, not viable bacteria
Can be used during or following abx treatment***
Treatment of Haemophilus influenzae
Treated typically with ß-lactams (ie augmentin)
If resistance or highly invasive infections, consider 3rd gen cephalosporins (will also cross BBB)
Preventable through the use of one of three different Hib conjugate vaccines
Smallest free-living bacteria
Mycoplasma pneumoniae
Cause of atypical CAP
Due to its lack of cell walls, Mycoplasma pneumoniae is …
Pleomorphic in shape
Has a “fried egg” appearance in culture on many different media
Bacteria with plasma membranes containing sterols
Mycoplasma pneumoniae
Aerobic and looks like our cholesterol so easily evades immune system
SSx of Mycoplasma pneumoniae infection
Non-productive cough that lasts 1-2 months, fever (but not usually in children under 5), crackles, headache and chest pain
Relapses common - infection does not produce long lasting immunity
Pathogenesis of Mycoplasma pneumoniae infection
Organism adheres to epithelium and releases hydrogen peroxide, resulting in damage to epithelium
Prevents clearance of airway and results in colonization of airways
Evades immune system by fusing to host cell membrane (via sterols), disguising itself
Can also cause otitis, rhinitis, pharyngitis, and tracheobronchitis
Mycoplasma pneumoniae generally targets people in what age range?
5-20 years
Very common transmission between family members, outbreaks common in crowded conditions
Humans are the only reservoir
Transmission of Mycoplasma pneumoniae is via…
Respiratory droplets (person-to-person)
How is Mycoplasma pneumoniae diagnosed?
Chest X-ray: patchy infiltrates (not lobar consolidation)
Culture from sputum
COLD AGGLUTININ ASSAY - detects IgM antibodies that bind to the I antigen on the surface of RBCs at 4˚C (not specific though)
DOC for Mycoplasma pneumoniae
Azithromycin/Tetracycline
Tiny, non-motile, coccoid shaped bacteria that exist as obligate intracellular parasites and cause atypical pneumonia
Chlamydophila pneumoniae
They’re gram-negative, in case you were wondering
Chlamydophila pneumoniae exists in what two forms?
Elementary bodies (EB) - the infectious form
Reticulate bodies (RB) - the intracellular form
How does the Chlamydophila pneumoniae life cycle work?
Chlamydophila elementary body enters lung cell
Elementary body becomes reticulate body
Replication occurs
Reticulate body becomes elementary body and is released to reinfect other cells
Clinical SSx of Chlamydophila pneumoniae infection are a result of what?
Direct tissue destruction during intercellular bacterial replication, in addition to inflammatory response
Possesses at least 2 exotoxins as well
Primary response is by neutrophils (immunity not long lasting)
Patients may be asymptomatic or present with mild symptoms (persistent non-productive cough and malaise, with UNILATERAL lower lobe involvement)
Chlamydophila pneumoniae occurs mostly in …
Adults 60+ years
Transmitted person-to-person via respiratory droplets (humans are the only reservoir)
The cell culture for this bacterium is difficult and time consuming
Chlamydophila pneumoniae
Dx relies on clinical manifestations and history, along with cell culture and microscopy (looking for inclusions), serology, and PCR
DOC for Chlamydophila pneumoniae
Tetracycline/erythromycin
How did Legionella pneumophila get its name?
Outbreak at an American Legion Convention in Philadelphia in 1976
There are 48 species and 70+ serogroups in genus Legionella
90%+ of all human infections result from one species (Legionella pneumophila), most are serogroup 1
What does Legionella pneumophila look like?
Thin, gram-negative pleomorphic bacillus
Also has:
• Fimbriae
• Single, polar flagellum
• ß-lactamase producer
Humans are infected with Legionella pneumophila by…
Inhalation of aerosolized contaminated water
What is the pathogenesis of Legionella pneumophila?
Bacterial cells are opsonized with C3b, facilitating their phagocytosis, but survive intracellularly by inhibiting phagolysosome fusion
Bacterial replication occurs inside phagosome
Host cell is killed when phagosome lyses, releasing toxic enzymes
Bacteria are released upon cell lysis
A self-limited illness resulting from Legionella pneumophila infection with Sx lasting 2-5 days and resolving spontaneously w/o treatment
Pontiac Fever
SSx: Fever Chills Malaise Myalgia HA No Sx of PNA
A severe, acute atypical PNA with a high mortality rate (up to 75% w/o treatment), acquired by inhalation of aerolized bacteria
Legionnaires’ Disease (Legionella pneumophila)
2-10 day incubation period —> abrupt onset of Sx:
Fever
Chills
Dry/nonproductive cough
HA
GI and Neuro Sx** differentiates it from other PNAs
Death is due to shock or respiratory failure
Pathogenesis of Legionnaires’ Disease
Entry of bacilli into macrophages —> multiplication inside macrophage —> death of macrophages —> release of chemotactic factors —> influx of monocytes and PMNs —> increased serum proteins, deposition of fibrin in alveoli, and release of enzymes and cytokines
End result? Acute FIBROPURULENT NECROTIZING PNA
Where is Legionella pneumophila widespread?
Moist environments
Rivers, streams, potable water, sewage, shower heads, cooling towers, other public water supplies
In nature, the bacteria survive and replicate within protozoan
Risk factors for Legionella pneumophila infection
Presence of a LARGE inoculum (not very virulent) AND
Any compromise in pulmonary and/or immune function: • Smoking • Chronic heart disease • Chronic lung disease • Immunosuppression • Elderly •Alcoholics
Immunity appears to be long-lasting
What medium is used for Legionella pneumophila cultures?
Buffered Charcoal Yeast Extract (BCYE) - it is the only clinical isolate that will grow on it
How else is Legionella pneumophila diagnosed if not with a culture?
Rapid test for antigen in the urine (EIA test)
High sensitivity, but only detects infections with serotypes 1
Treatment for Legionella pneumophila
DOC: Levofloxacin or other fluoroquinolones
If <8 years, give em a z-pack
Severe disease requires careful management and supportive therapy
No treatment necessary for Pontiac fever
Describe Pseudomonas aeruginosa
Gram-negative, aerobic, motile bacillus with a single flagellum
Clinical isolates possess pili as well
Blue-green in color due to Pyoverdin and Pyocyanin
Primary bacterium used in bioremediation
Pseudomonas aeruginosa
For treatment of sewage, oil spills etc to break down bacteria
What is Pyocyanin
“Blue pus” pigment in Pseudomonas aeruginosa
Catalyze ROS production —> tissue damage
VIRULENCE FACTOR
What is Pyoverdin
Green fluorescent pigment found in Pseudomonas aeruginosa
Not a virulence factor but gives it a very distinctive appearance
What are the virulence factors for Pseudomonas aeruginosa?
Pyocyanin (ROS production)
Exotoxin A (A-B toxin —> inhibition of protein synthesis —> ciliastasis and immunosuppression)
Elastases (LasA and LasB) - work synergistically to destroy elastin in the lungs (lose ability to expand/contract —> no gas exchange)
Alginate (mucous polysaccharide/slime layer) - inhibits mucociliary escalator
Pili (attachment to host)
LPS (endotoxin) —> fever, shock, DIC, tissue necrosis
Where does Pseudomonas aeruginosa come from
Widespread in the environment - inhabits plants, water, and moist soil
Frequent or transient carriage on skin and in feces
An opportunistic pathogen in the hospital
Transmission occurs via fomites, plants, fruits, hands
Because Pseudomonas aeruginosa is not very virulent, infection requires what?
A significant break in normal defenses - generally in a immunocompromised host
Can cause a variety of infections: UTI PNA (esp after vent) Eye, ear, and skin (from contaminated hot tub, contact lens) Burn patients CF (common cause of death)
What media support the growth of Pseudomonas aeruginosa
BAP and MacConkey
Will produce a water-soluble blue-green pigment
Fruity smell
Patient may fluoresce or it may tinge sputum/pus
Treatment of Pseudomonas aeruginosa
DO SUSCEPTIBILITY TESTING - MDR strains common
Synergistic drug combo required for successful treatment
Current DOC: Cefepime + Levofloxacin
Avoid broad-spectrum abx (b/c they suppress normal flora)
