Pneumonia Flashcards
Pneumonitis
Condition characterized by inflammation of parenchyma of lung
Due to many causes: • Viral infection • Chronic or recurrent bacterial infections • Radiation therapy • Sepsis • Adverse drug reactions • Hypersensitivity reactions • Smoking • Exposure to chemicals
Pneumonia: Definition
o Condition characterized by inflammation of parenchyma of lung
o Causes alveoli to fill with fluid → consolidation → decreased gas exchange
Pneumonia: pathogenesis
- Colonization of upper respiratory tract
- Followed by injury to mucociliary excalator
- Organisms travel down respiratory tree = reproduce in alveoli → inflammation of parenchyma
With aspiration = oral flora transferred to lungs (because cough reflex is diminished and/or vomitus has been inhaled)
Some situations: organism is inhaled directly into lower respiratory tract
• Ex: mycobacterial infection, legionellosis, fungal pneumonias, some viral diseases
Some cases (rare): from hematologic seeding of lungs by bacteria in blood stream
• Septic emboli and surrounding pneumonia and pneumonitis
• Typically involved lower segments of lungs (greater vascular flow)
• Ex. S. aureus (especially as a complication of right-sided endocarditis)
Pneumonia: clinical manifestations
- Fever, chills, SOB
- Cough may be dry or productive of purulent sputum
- Hemoptysis uncommon
- Pleuritic chest pain is relatively common
- Anorexia and headache may occur
- Systemic symptoms: weight loss or night sweats = suggest tuberculosis or fungal etiology
Pneumonia: exam findings
- Ronchi and wet rales over affected areas
- Sounds may be unremarkable if area of consolidation not close to chest wall
- Egophony and fremitus = suggest lung consolidation
- Dullness to percussion → pleural effusion
- All symptoms associated with other conditions = cannot rely on symptoms to diagnose pneumonia (need imaging)
Pneumonia: classification schemes
Clinical situation Community acquired pneumonia (CAP) Hospital acquired (HAP) o Occurs 48 or more hours after admission Ventilator associated (VAP) o Occurs 48-72 hours after intubation Healthcare associated (HCAP) o Prior hospitalization (within 90 days) o In nursing home or long term care facility o Received IV antibiotics within 30 days
Radiologic appearance Lobar pneumonia o Involves single lobe o Suggest a typical bacterial pathogen Interstitial pneumonia and pneumonitis o Involves space between alveoli o Suggests viral cause, Pneumocystis jiroveci, or an atypical bacteria Nodules and cavities o Suggests a mycobacterial or fungal cause
Pneumonia: pathologic findings
Bronchiolitis obliterans organizing pneumonia
o AKA Cryptogenic organizing pneumonia
o Associated with inflammation of small airways of lung
Eosinophilic pneumonia
o Seen with parasites and autoimmune disorders
Lipid pneumonia
o Inhalation of an oil
Necrotizing pneumonia
o Necrosis of lung parenchyma
o Typically caused by oral anaerobes
Microbiologic characteristics Typical o Organisms show up on Gram stain Atypical o Sputum Gram stain shows neutrophils but NO organisms
Pneumonia: diagnosis and lab testing
- Need imaging study (x-ray or CT) = show consolidation
- Sputum for Gram stain and culture
- Processed only if appropriate specimen from lower respiratory tract (numerous neutrophils and relatively few squamous epithelial cells)
- May require special stains and media
- Blood cultures
- Pleural fluid analysis and culture
- Urinary antigen testing
Explain the general properties and the life cycle of Chlamydia and Chlamydophila species
General properties
o Obligatory intracellular Gram-negative microorganisms
• Intracellular so often not seen on Gram-stains
o Form inclusions (phagosomes containing a collection of EBs and RBs)
o Unique life cycle: Elementary body–Reticulate body
o Rigid but lack peptidoglycan
• No response to anti-cell wall antibiotics
o Common liposaccharide group antigen in outer membrane
o Tendency to cause persistent infections
o Immune defense participates in the tissue destruction
Life cycle:
Elementary body (EB) attaches to surface of susceptible cell
• Passively engulfed
• Prevents fusion of lysozymes with phagosome
EB reorganizes into RB
• Metabolically active (uses host’s phosphate compounds = an energy parasite)
• Starts to divide
When many RBs present within inclusion → condense into infectious EBs
o Inclusion bursts → cell dies; daughter EBs free to infect new cells
o Entire process takes 2-3 days
Compare and contrast the properties of the elementary body and the reticulate body found in Chlamydia and Chlamydophila species.
EB: small dense particle infectious non-replicating released when cell ruptures
RB: large loose particle non-infectious multiply by binary fission found inside of cells
Describe the diseases associated with infections caused by Chlamydia and Chlamydophila species
Chlamydia trachomatis Associated diseases: STDs: • Nonspecific urethritis (in men) • Mucopurulent cervicitis (in women) • Pelvic inflammatory disease (PID) • Endometritis • Epididymitis • Lymphogranuloma venereum (LGV) Eye infections: • Trachoma (chronic infection resulting in blindness) • Ophthalmia Neonatorum (acute conjunctivitis in newborns)
Chlamydophila pneumoniae
o Transmission: person to person via respiratory droplets
Associated diseases:
Community acquired pneumonia
• Causes 10% of cases in young adults
• Symptoms: sore throat, prolonged dry cough, low-grade fevers
• Respiratory tract infections may last several months
• Diagnose when 4x rise in antibody titer in serum samples taken 3-4 weeks apart
Bronchitis
Sinusitis
Acute otitis media
Possibly atherosclerosis
Chlamydia psittaci
o Unusual cause of pneumonia (AKA parrot fever)
o Tends to be more severe than C. pneumonia
o Transmission: via inhalation of EB from infected bird or its droppings
• Infected birds may not appear to be ill
• Organism is rarely transmitted person to person
o Incubation period is 1-2 weeks
o Symptoms (last 5-6 weeks): fever, chills, headache and dry cough
o Long term complications can occur (cardiac and CNS involvement)
o Can cause both asymptomatic and complex infections
• 5% mortality
Diagnosis:
• Confirmed by paired serologic data showing 4-fold rise in antibody titer
Treatment:
• Either a tetracycline antibiotic, a macrolide, or a fluoroquinolone
Long term complications of Chlamydia and Chlamydophila infections
o Trachoma: blindness
o PID: infertility, chronic pain, ectopic pregnancy
o Urethritis: reactive arthritis
o Cervicitis: C. trachomatis serotype G may be linked to cervical cancer
Discuss the general properties attributable to Mycoplasma species.
o Smallest known genome of the “free-living” organisms
o Lack many metabolic pathways in other bacteria = require complex media to grow in lab
Unique = form a separate taxonomic class
• Known as the mollicutes (means “soft skin”)
Lack peptidoglycan
• Pleomorphic because lack backbone that maintains eubacteria shape
• Resistant to antibiotics targeting bacterial cell wall
Smallest organism capable of reproducing in broth and agar (diameter = 300 nm)
• On PPLO (pleuropneumonia-like organism) agar = form tiny colonies barely visible to naked eye
• In broth = may form filamentous structures that look like fungal mycelium (= name “myco”)
o Produce hydrogen peroxide and superoxide
o Inhibit host cell catalase → increased concentraton of peroxide → host cell damage
o Activate macrophages and stimulate cytokine production
o Can adhere to epithelial surfaces via protein called P1 adhesion
• Binds sialic acid residues on epithelial cells
• Result= cessation of ciliary motion → dry cough
List the major mycoplasma species in humans:
o Mycoplasma genitalium
o Mycoplasma hominis
o Mycoplasma pneumoniae
Mycoplasma genitalium
- Frequent cause of community acquired pneumonia in people 17-44 years
- “Walking pneumonia)
- Endemic cases happen regularly every 3-5 years
- Transmission: respiratory droplets from person to person
- Incubation period typically 20 days (range 11-28 days)
- Attack rate in families is 17-66% (high)
Diagnosis is rarely confirmed in practice
• Symptoms are mild: dry cough, dyspnea, fever
• Cultures on PPLO agar takes weeks
• PCR promising but test not widely available
• Serology is helpful with up to 85% of presenting patients reportedly having M. pneumoniae specific IgM (but many question value of this done alone)
Cold agglutinins
• Antibodies directed at blood group I
• Appear before specific Ab’s appear
• Seen in 34-68% of patients with M. pneumoniae
• But low sensitivity and specificity of test
Combination of specific IgM and cold agglutinins = best way to diagnose M. pneumoniae infection
Other clinical manifestations of M. pneumoniae infection
• Respiratory tract: acute bronchitis, sinusitis, pharyngitis
• Skin and mucosa: rash, urticaria, erythema multiforme, Steven-Johnson syndrome
• CNS: meningitis, cerebellitis, acute psychosis
• Other: bullous marygitis (blisters on tympanic membrane), hemolytic anemia (cold agglutinins hemolyse RBCs)
Mycoplasma hominis
- Casues: tubo-ovarian abscesses, salpingitis, PID
* Fried Egg appearance on PPLO agar
Mycoplasma pneumoniae
• Associated with nonspecific urethritis and PID
Treatment of mycoplasma infections
o Either doxycycline, a macrolide, or a fluoroquinolone
o No vaccine exists for any of these microorganisms
General properties of Legionella species
o Slender, motile, aerobic rods (occasionally look like coccobacilli)
o Do not have a capsule
o Do not form spores
o Technically = Gram-negative but take up stain poorly
o Nutritionally fastidious and difficult to grow
• Need buffered charcoal yeast extract (BCYE) to grow
o More than 50 species and 70 serogroups
• About 20 associated with human disease
• Legionella pneumophila serogroup causes about 80% of human infections
Legionella: epidemiology
o Worldwide distribution
• In natural bodies of fresh water and moist soil
o Can withstand heat and chlorination = can enter municipal water systems and proliferate
o May cause nosocomial infections
o Other organisms aid Legionella growth and distribution:
• Other bacteria may provide nutrients
• Free living amoeba provide intracellular “safe harbor”
o Causes infection all year but peaks in summer and autumn
o Severity increases in elderly and people with respiratory problems
Legionella: transmission
o Via inhalation of respiratory droplets
o Important to control environmental water sources (indoors and outdoors)
o No person-to-person transmission ever documented
Legionella: pathogenesis
o Inhaled organisms ingested by alveolar macrophages
o Engulfed by phagosomes
• Inhibit fusion with lysosomes
o Organisms proliferate within cells → rupture = spread
o Rupture causes inflammation → tissue destruction in lungs
Legionella pneumophila: major diseases
Acute pneumonia
• 5% of community acquired pneumonia
• 30% of nosocomial pneumonia
• Multiple lobes may be involved; pleural effusions are commonly seen
• Initial symptoms: headache, fever, malaise, muscle aches
• Few days later: dyspnea, non-productive cough; followed by abdominal pain, diarrhea, and confusion
Symptoms:
• Range from very mild illness to frank respiratory failure
Mortality:
• Healthy people: approximately 10%
• Immunosuppressed people: 50%
Incubation period: typically 2-10 days (may reach 28 days)
Diagnosis:
• Sputum samples = neutrophils without microorganisms (because take up Gram stain poorly)
o May be visualized with DFA stain (monoclonal Ab tagged with fluorescein dye)
• Sputum cultures on BCYE = may take up to 14 days to turn positive
• Four fold increase in Ab titer may be used (4 weeks apart)
**Urine Legionella antigen test
o Most practical test
o Detects presence of soluble Legionella antigen in urine using ELISA test
o Infected people = excrete Legionella antigen as soon as symptoms develop
• May persist for weeks to months
o Only specific for Legionella pneumophila serogroup 1 (causes 80% of human infections)
Treatment:
• Reduces morbidity and mortality
• Macrolides, tetracyclines or fluoroquinolones
• Severe illness: sometimes use combination therapy
Pontiac fever • Acute influenza-like illness with high attack rate • > 90% develop illness Symptoms: • High fever • Myalgia • Arthralgia • Headache lasting 2-5 days • No respiratory symptoms Negative chest x-ray Symptoms due to hypersensitivity reaction to Legionella proteins Treatment: • None needed for Pontiac fever (self-limiting)
Prevention of Legionella
No effective vaccine
Find and treat environmental water sources (especially hospitals)
• Superheating
• Copper-silver ionization (metal ions disrupt cell membranes → kill organism)
• Hyperchlorination no longer used
Compare and contrast acute pneumonia with Pontiac fever caused by L. pneumophila.
- Pontiac fever = high attack rate
- Treating pneumonia = reduces morbidity and mortality
- No treatment needed for Pontiac fever
Community acquired pneumonia
Five common bacterial causes: (2 typical and 3 atypical) o Streptococcus pneumoniae o Haemophilus influenza o Legionella pneumoniae o Mycoplasma pneumoniae o Chlamydophila pneumoniae
Treatment focuses on these 5 common causes
• Cannot be distinguished on clinical appearance and presentation
Drug therapy depends on illness severity o Fluoroquinolone (levofloxacin or moxifloxacin) alone or beta-lactam + macrolide (erythromycin, azithromycin, clarithromycin) o Typical treatment for mild CAP = either doxycycline, macrolide or a quinolone
Vaccines available for Streptococcus pneumoniae and Haemophilus influenza
o No vaccine for 3 atypical organisms
