Download Infectious Lung Diseases

Respiratory Pathophysiology: Pulmonary Infections (Krell)
PNEUMONIA:
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Definition: inflammation of gas exchanging areas of the lungs/lower respiratory tract
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Epidemiology:
10% of all hospitalizations
Complicates hospital course in 5% of all patients
5th leading cause of death in US
Leading cause of death from infectious disease in US

Normal Host Defenses:
Mechanical:
o Curved shape of upper airway
o Vibrissae (nose hair)
Reflexes:
o Coughing/sneezing (expel material)
Mucociliary Escalator:
o Unidirectional beating of airway cilia to move blanket of mucus upward
o Brings trapped material to be swallowed or expectorated
Cellular:
o Alveolar Macrophages: phagocytosis and chemotacxin release
o Immunologic Reactions:

T Cells: cell mediated immunity
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B Cells: Ab production
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Alterations in Host Defenses Predisposing to Pneumonia:
Age:
o Very young (immature immune system)
o Very old (depressed immune function due to debilitation or disease)
Debilitation or malnutrition
Depressed level of consciousness:
o Neurologic illness or injury
o Seizures
o Drug overdose
o Anesthesia
Airway abnormalities:
o Trauma
o Inhalant injury
o Obstruction
Problems with mucociliary function:
o Abnormal mucus (CF)
o Poor ciliary function

Inhibition of ciliary motion (cigarette smoke, pollutants, alcohol, anesthesia, viral infections,
COPD, some drugs)
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Immotile or dysfunctional cilia syndromes
Other Diseases:
o Cancer (depressed immunity, obstruction, debilitation)
o CHF
o Diabetes (altered upper airway flora, decreased immune cell function)
o Viral infections (affects mucociliary function, depresses PMN function)
o Alcoholism (debility, malnutrition, depressed level of consciousness, poor ciliary function)
Immunosuppression
o Primary: congenital defect in any system component
o Secondary:

Neutropenia: drug induced, irradiation, malignancy
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Defective PMN Function: malignancy, uremia, burns, diabetes, steroids
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Depressed Cell Mediated Immunity: AIDS, steroids, uremia, cancers, chemotherapy

Depressed Humoral Immunity: splenectomy, sickle cell disease, malignancy, irradiation,
chemotherapy, malnutrition

Modes of Transmissions:
Aspiration of Oropharyngeal Organisms: most common*
o Pneumococcus: most common bacterial pneumonia (part of normal oral flora)
o Anaerobes: live in gingival crevices
o Altered upper airway flora:
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Colonization with pathogens (gram negatives) in hospitals and nursing homes
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People using needles (IV drug abusers, diabetics, dialysis patients)
o Predisposition:

Altered state of consciousness

Neuromuscular illness
Inhalation of Airborne Organisms:
o Organisms:

Mycoplasma

TB

Legionella
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Fungi
o Important Factors:

Size of inoculums

State of host defenses
Hematogenous Spread: not very common
o Bloodborne infections: spread from elsewhere in the body (ie. IV drug users, infected IV lines)
Lymphatic Spread: uncommon
o Lymph borne infection: from another body site
CLASSIFICATION OF PNEUMONIAS:

By Organism: bacterial, viral, fungal etc.

By Host Factors: this classification is important because it suggests the potential organisms (start empiric therapy
with antibiotics based on these likely organisms while cultures are pending)
Community Acquired: seen in normal population (ie. nursing home)
Nosocomial: acquired due to hospital environment
o Colonization of upper airway by pathogens
o Medications, anesthesia may lead to aspiration
o Invasive devices can become colonized
o Lack of handwashing
o Contaminated respiratory equipment
Immunocompromised Patients:
o Due to underlying disease (cancer, AIDS)
o Due to therapy (chemotherapy, radiation, steroids, immunosuppressants)
o See infections with unusual pathogens and common bacteria

Unusual pathogens include:
 Fungi
 Atypical TB
 Protozoans (Pneumocystis)

By Radiographic Appearance: may be distinctive and may help determining potential causative organisms (only a
rough guide, not a diagnostic tool)
Lobar Pneumonia:
o Consolidation (alveolar filling process)
o Homogenous white area following anatomic segments (lobes)
o Air bronchogram shows air filled airway outlined by consolidated lung
o Classic presentation of pneumococcal pneumonia
Bronchopneumonia
Interstitial Pneumonia
Cavitary Lesions
Pleural Effusions
BACTERIAL PNEUMONIAS:

Classic Clinical Picture:
Acutely ill with fever
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Shaking and chills at onset
Cough with sputum production
Chest pain, chest tightness, and dyspnea may be present
Patient History:
Rapid onset and course (may be helpful)
Determine if CAP, HAP, or immunocompromised
Determine if risk factors for aspiration exist
Determine patient contacts
Recent travel, occupational or environmental exposures
Exam:
General: fever, tachycardia, tachypnea
Lobar Pneumonia:
o Percussion dullness
o Bronchial breath sounds
o Increased tactile/vocal fremitus
Patchy/Interstitial Pattern:
o Rales or crackles
Effusion:
o Percussion dullness
o Decreased transmission of sounds and fremitus
Chest X-Ray: may assist in differential diagnosis (see above)
Sputum:
Color/Consistency:
o Rusty (pneumococcal)
o “Currant jelly” (Klebsiella)
o Creamy yellow (Staphylococcus)
o Foul odor (anaerobes)
o Lots of PMNs
Gram Stain:
o Need adequate specimen:

<10 epithelial cells/LPF
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>25 PMNs/LPF
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Ratio of PMNs:Epithelial cells ~5:1
o In the ideal situation, identify one single or one prominent organism
o Certain pathogens cannot be seen with Gram stain
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Mycoplasma

Legionella
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TB

Viruses
Sputum Culture:
o Difficult to sort out contaminants from pathogens
o Organism may not grow on routine media
Other Means:
o Cultures from blood or pleural fluid
o Serology or skin testing
o Invasive diagnostics (bronchoscopy, surgical biopsy)
Specific Bacterial Pneumonias:
Pneumococcal Pneumonia:
o Epidemiology:

Most common cause of bacterial pneumonia

Can colonize oropharynx of healthy people
o Clinical Picture:

Acute onset of shaking chills (may follow URI)
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Fever, dyspnea, pleuritic chest pain
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Cough with rusty colored sputum
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Leukocytosis (increased WBC count)
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Signs of consolidation on exam (chest XR shows lobar consolidation)
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Gram stain shows G+ lancet shaped diplococci (intracellular)
o
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Treatment:
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Antibiotics: macrolide + 3rd generation cephalosporin (some resistant strains exist)
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Vaccine: pneumovax
o Signs Indicating Poor Outcome:
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Bacteremia (greater burden of infection)
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Hematogenous spread (meningitis, endocarditis, arthritis)
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More than 1 lobe involved
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Type 3 serotype (more virulent than others)
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Very young or very old age
Mycoplasma Pneumonia (“Walking Pneumonia”):
o Epidemiology:

Common cause in otherwise healthy young people
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Outbreaks (family, school, military)
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Most common in fall and winter
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Spread by inhalation of infected aerosol
o Clinical Picture:
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Insidious onset of fever, headache, chills, malaise and other systemic manigestations
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Non-productive cough
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No leukocytosis
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Bullous myringitis (blisters on eardrum)
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Usually bronchopneumonia with patchy rales/crackles heard on exam (rarely consolidates)
 Patchy bronchopneumonia on chest X-ray
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Diagnosis by serology
 Organism does not gram stain well or grow on routine media (3 layered membrane
with no cell wll)
 Positive cold agglutinins test (not all patients)
o Treatment:

Macrolide OR tetracycline
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May resolve spontaneously if milder illness
Legionella spp.:
o Epidemiology:
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Presents as epidemics or as a nosocomial infection
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Common source of infection is contaminated water supply or air conditioning units
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Risk factors:
 Immunosuppression
 Smoking
 COPD
 Advanced age
 Male
 Cardiac disease
o Clinical Picture:
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High fever, recurrent chills, cough, diarrhea (GI involvement)
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Relative bradycardia (for degree of fever; normally, increase HR by 10bpm per degree of
fever increase)
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Electrolyte disturbances:
 Hyponatremia
 Hypophosphatemia
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Diagnosis:
 Chest X-ray shows varied patterns (no typical patterns)
 Does not stain by Gram stain (need silver or DFA stain)
 Serology
 Culture on selective media
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Course may be fulminant and systemic
o Treatment:
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Macrolides OR rifampin
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Aerobic Bacterial Pneumonias:
o Hemophilus influenzae:
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Risk Factors:
 COPD
 Alcoholics
 Sickle cell (asplenia)
 Immunodeficiency
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Clinical Picture:
 Large amounts of sputum
 Low grade fever
 Dyspnea and pleuritis
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Diagnosis:
 Sputum shows G- coccobacilli (intracellular)
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Treatment is fairly easy (cephalosporins, sulfa drugs, ampicillin)
o Klebsiella pneumoniae:
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Risk Factors:
 Alcoholics
 Diabetes
 Debilitation
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Clinical Picture:
 Abrupt onset of high fevers
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Diagnosis:
 Bulging fissure on CXR (lobar pneumonia)
 Sputum shows plump G- rod
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Treatment includes cephalosporins or AMGs
o Other Gram Negative Pneumonias:
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Cause mostly HAP (rare cause of CAPs)
 Nosocomial infections often caused by Pseudomonas
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Risk Factors:
 Alcoholics
 Diabetics
 Debilitation
 Immunocompromise
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Cause necrotizing and destructive infections with very high mortality rate
o Staphylococcus aureus:
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CAP (IV drug users, people with colonization of nasopharynx)
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Elderly (often follows the flu)
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Nosocomial infections (IV devices)
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Sputum shows G+ cocci in clusters (easily cultured)
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Clinical course involves multiple cavitary lesions , lung destruction and pleural complications
Anaerobic Pulmonary Infections:
o Mechanism: aspiration
o Predisposing Factors:
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Alcoholism
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Impaired level of consciousness (drugs, seizures, CNS insult)
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Dysphagia
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NM disease
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Poor oral hygiene (ie. dental caries)
o Organisms: usually mixed flora (Fusobacterium, Bacteroides, Peptostreptococcus)
o Clinical Picture:
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Foul smelling sputum
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Subacute/chronic course
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History suggestive of aspiration
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Sweats, malaise, weight loss, leukocytosis
o Spectrum:
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Lung Abscess: occur about 12 days after aspiration (necrosis/liquefaction of tissue)
 CXR shows cavity with air-fluid level
 1/3 extend into pleural space (forming an empyema)
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Necrotizing Pneumonia: multiple small cavities
 Patient very ill with high fever and leukocytosis
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Empyema: infection in the pleural space
o Treatment:
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Antibiotics (penicillin, clindamycin- Abx require long course)
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Drainage (chest clapping, cough, postural drainage, chest tube)
Effusion Related Infections:
Parapneumonic:
o Occur in relation to pneumonias
o Sterile exudates on culture
o Treating pneumonia treats the effusion
Empyema:
o Direct or other spread of infection to pleural space
o Organisms seen and cultured from exudates
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Fluid also contains a lot of PMNs, with low glucose and low pH
o Treatment involves antibiotics and pleural space drainage
FUNGAL PNEUMONIAS:
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Coccidiodomycosis:
Epidemiology:
o Endemic Areas: SW USA, northern border of Mexico, San Joaquin Valley (California)
o Life Cycle:
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Germinates as arthrospore in the soil (infectious to humans)
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Tissue form in spherule (contains endospores)
Immunology:
o Skin Testing: coccidiodin (produces induration)
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Negative to positive skin test means new infections
 Will be positive between 3 days-3 weeks of illness
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Positive to negative skin test means severe or disseminated disease
o IgM Testing: tube precipitin or latex particle agglutination
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Positive 2-4 weeks into illness
o IgG Testing: complement fixation
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Positive ~ 8 weeks after infection (results are diagnostic and prognostic)
 Very high titers result in high chance of disseminated disease
o Culture: dangerous (airborne infection via arthrospores)
Clinical Patterns:
o Asymptomatic: ~60% of cases (only evidence of infection is immunologic)
o Primary Coccidiodomycosis:
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Low grade fever, cough, chest pain, headaches, malaise, joint aches
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Valley Fever is a specific subtype most often seen in young women
 Skin lesions (particularly erythema nodosum)
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Clinical Course:
 Milder than bacterial pneumonia
 Most recover without therapy in ~8 weeks
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Risk Factors for Dissemination:
 Age (over 50 or under 5)
 Immunosuppression
 Race (African Americans, Native Americans, Mexicans and Filipinos higher risk)
o Persistent Chronic Infection: uncommon
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Infection lasting greater than 8 weeks
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May require anti-fungal therapy
o Disseminated Disease: can affect any organ system
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Often see change in skin test from positive to negative
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Skin is the most common system effected
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Worst outcome is meningitis (fatal without treatment)
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Therapy IV anti-fungals
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Same risk factors as above
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Histoplasmosis:
Epidemiology:
o Endemic Areas: worldwide distribution with centers around Mississippi, Ohio, Missouri and Tennessee
River Valleys
o Life Cycle:
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Infectious microconidia (spore) lives in soil
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Fowl and bat droppings increase growth of fungus
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Tissue form is narrow necked budding yeast
Immunology:
o Skin Testing: not useful for making diagnosis because too many people have + reactions
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Can also cause false positive serologic tests
o Serologic Testing: detection of Ab by immunodiffusion
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Helpful diagnostically but not prognostically
o Culture: difficult to grow
Clinical Patterns:
o Asymptomatic: majority of cases
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CXR may show calcifications from old infections
o Symptomatic:
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Non-specific malaise, headache, fever, nonproductive cough, pain on swallowing
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May recover without treatment
o Chronic Histoplasmosis:
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Seen in patients with severe underlying disease (ie. COPD)
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May need antifungal therapy if pulmonary status deteriorates
o Disseminated Histoplasmosis:
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Rare opportunistic infection that is fatal if untreated
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Occurs in patients with decreased CMI
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Sites of dissemination include bone marrow, LNs, GI tract, and oropharynx
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High dose IV antifungal treatment is required
Blastomycosis:
Epidemiology:
o Endemic Areas: not well known (may be similar to histo)
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Outbreaks reported in south and south-central US and in regions around Great Lakes
o Life Cycle:
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Dumbbell shaped spores become airborne from soil
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Reproduce in tissue as broad necked budding yeast
Immunology:
o Skin Testing: not useful (more likely to indicate histoplasma)
o Serologic Testing: not useful (high titer may suggest illness in someone whom the infection is not
suspected)
o Culture: definitive diagnosis (fast growing and easy to culture)
Clinical Patterns:
o Asymptomatic: we presume that the majority of infections are asymptomatic OR patients recover
without therapy
o Acute:
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Abrupt onset high fever, and productive cough
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Most recover spontaneously (in about 4 weeks)
o Chronic: requires antifungal therapy
o Disseminated:
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Infects lungs, skin (ulcerated lesions), bone (destructive lesions)
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May also cause prostatitis and epididymitis in males
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Treatment with IV antifungals
Aspergillus:
Epidemiology:
o Ubiquitous
o Type of disease it causes in humans related to status of the patient
Immunology:
o Skin Testing: valuable in acute forms of aspergillosis (immediate type I hypersensitivity)
o Serology: IgE Abs found in patient with acute illness or fungus balls (may also see IgG)
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Clinical Patterns:
o Hypersensitivity Pneumonitis/Extrinsic Allergic Alveolitis:
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Cough, dyspnea, fever and chills within 4-6 hours of exposure to spores
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Responds well to corticosteroids
o Allergic Bronchopulmonary Aspergillosis (ABPA):
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Occurs in patients with longstanding asthma
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Manifestations:
 Worsened airflow obstruction
 Eosinophilia
 Positive skin test and serology
 Elevated serum IgE
 Migratory chest XR infiltrates
 Cough up brown mucus plugs
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Treatment with corticosteroids
o Aspergilloma (Fungus Ball):
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Colonization of PRE-EXISTING cavity (ie. old TB)
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Can cause bleeding and erosion
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May need to remove surgically
o Invasive Aspergillosis:
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Only seen in immunocompromised patients
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Immunologic testing is not of value (culture for diagnosis)
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Treat with more than 1 IV antifungal (very high mortality)
COMMUNITY ACQUIRED PNEUMONIA:

General:
Grouping these patients by age, presence of other medical illnesses and severity of pneumonia helps with
determining initial therapy and prognosis
Streptococcus pneumoniae is the most common organism in all four groups of CAP
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Group 1:
Classification:
o Outpatient pneumonia
o No co-morbidity
o Age <60 years old
Mortality: <5%
Organisms:
o Streptococcus pneumoniae
o Mycoplasma pneumoniae
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Group 2:
Classification:
o Outpatient pneumonia
o Comorbidity and/or age >60 years old
Mortality: <5%
Organisms:
o Streptococcus penumoniae
o Respiratory viruses
o Hemophilus influenzae
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Group 3:
Classification: hospitalized with CAP
Mortality: 5-25%
Organisms:
o Streptococcus pneumoniae
o Hemophilus infleunzae
o Polymicrobial (including anaerobes)
o Gram negative bacilli
o Legionella
o Staphylococcus aureus
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Group 4:
Classification: severe pneumonia (hospitalized, ICU)
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Mortality: up to 50%
Organisms:
o Streptococcus pneumoniae
o Legionella
o Gram negative bacilli
o Respiratory viruses
NOSOCOMIAL PNEUMONIAS:
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Epidemiology: 15% of all pneumonias (high cost, morbidity and mortality)

Mechanisms of Infection:
Altered upper airway flora (colonized with G- and others)
Aspiration of pathogens
Organisms from hospital environment are likely to be resistant to therapy
Patients have one or more risk factors decreasing normal host defenses

Organisms:
Enteric Gram Negative Bacilli: 60%
o E.coli, Klebsiella, Enterobacter, Pseudomonas, Serratia, Prosteus
Staphylococcus aureus: 10%
Legionella
Others
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Goals:
Prevention
Recognition of patients at high risk
Prompt recognition and treatment of infections
IMMUNOCOMPROMISED HOSTS:

Organisms:
General:
o Most infections are routine G+ and G- bacteria

May have atypical presentations

Prophylactic Abx often used in these patients
Opportunistic Infections:
o Definition: organisms that are not pathogenic in a normal host cause disease in immunocompromise
o Fungal Infections:
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Aspergillus (esp. in hematologic malignancies)
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Candida
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Dissemination of normally self-limited infections (Histoplasma, Coccidiomycosis)
o Viral Infections:

Example Scenarios: AIDs or post transplant

CMV: most commonly seen
 Source:
o Donor blood or organ
o Reactivation of dormant infection in host
 Clinical: fever and interstitial pneumonia
 Diagnosis:
o Viral inclusions in cells
o Cultures
o Monoclonal Abs
 Treatment: supportive care, immune replacement or antivirals
o Protozoan Infections:

Pneumocystis carinii:
 AIDS: slowly progressive infection (fever, cough, dyspnea, infiltrative CXR)
 Leukemia (Kids): more fulminant downhill course
 Diagnosis: organisms in secretions or tissue
 Treatment: TMP/SMX (first line); IV pentamidine if can’t tolerate