Jackson: Lower Respiratory Tract Infections Flashcards
1
Q
Lower Respiratory Tract Infections
Children vs adults:
A
• Age is a key determinant for pneumonia:
o Children: viruses are primary causes; bacteria cause secondary infections
o Adult: depends on a variety of risk factors
2
Q
Adult pneumonia may be CA or HA/Nosocomial
CA Risks:
HA Risks:
A
o CA Risks: alcohol abuse, occupational exposure, underlying condition
o HA Risks: immunocompromise and mechanical ventilation
3
Q
Atypical pneumonias are caused by:
also defined as:
A
• Atypical pneumonias are caused by a pathogen other than S.pneumo: also defined as primary pneumonia that did NOT involve an initiating viral infection
4
Q
Streptococcus pneumoniae (Pneumococcus) Virulence Factors (Relevant to Lower Respiratory Tract Infections): (3)
A
o Polysccharide capsule (90 serotypes)
o Pneumolysin
o Cell Wall TA and Peptidoglycan
5
Q
Streptococcus pneumoniae (Pneumococcus) Polysccharide capsule (90 serotypes): Prevents: (2) Facilitates: What confers host immunity?
A
o Polysccharide capsule (90 serotypes): primary virulence factor
• Prevents complement deposition (C3b)
• Prevents phagocytosis by alveolar macrophages
• Facilitates evasion of lung surfactant
• Abs to capsule confer host immunity
6
Q
Streptococcus pneumoniae (Pneumococcus) Pneumolysin: Damages membranes (related to?) \_\_\_\_\_\_\_is cell membrane receptor Acts on several cell types:
A
o Pneumolysin: sulfhydryl activated cytolysin (hemolysin)
• Damages membranes (related to SLO); subunits oligomerize in cell membrane to form a pore
• Cholesterol is cell membrane receptor
• Acts on several cell types (pulmonary epithelium, PMNs and monocytes)
7
Q
Streptococcus pneumoniae (Pneumococcus)
Pneumolysin
Role in Pathognesis
Evasion of:
Clearance from:
May permit:
Cell-bound form activates:
A
- Evasion of the immune response and clearance from nasopharynx
- May permit spread to bloodstream from alveoli (bacteremia)
- Cell-bound form activates complement, contributes to inflammation
8
Q
Streptococcus pneumoniae (Pneumococcus) Cell Wall TA and Peptidoglycan
Gram (+) Shock:
Activates:
Production of:
A
Gram (+) Shock: strong inflammatory response (similar to LPS in G negative); inflammation elicits fever and lung damage (bloody sputum)
- Activate alternate complement pathway
- Production of IL-1 and TNF alpha
9
Q
Streptococcus pneumoniae (Pneumococcus)
Exclusively a human pathogen:
Transmission:
A
Exclusively a human pathogen: many asymptomatic carriers (transient carriage also possible)
Transmission: person to person (droplet spread)
10
Q
Streptococcus pneumoniae (Pneumococcus)
Recurrent pneumococcal pneumonia:
Note:
A
Recurrent pneumococcal pneumonia: is a presenting manifestation of AIDS
Note: Most common cause of acute bacterial pneumonia in any age group
11
Q
Streptococcus pneumoniae (Pneumococcus)
Establishment of Organism in Lower Respiratory Tract:
Common causes of compromised cough:
A
Aspiration of pneumococci from middle respiratory tract
Compromised cough reflex permits entry into lower respiratory tract
- Common Causes: stroke, alcoholism, drugs, anesthesia, viral infection
• Alveolar Abs usually clear pneumococci from lower respiratory tract
12
Q
Streptococcus pneumoniae (Pneumococcus) Acute Pneumonia
Cough:
Inflammatory Response:
A
o Acute Pneumonia: infection of lung parenchyma
• Cough: with productive sputum (purulent material from alveoli)
• Inflammatory Response:
➢ Complement components increase vascular permeability (fluid accumulates)
➢ Disrupted gas exchange (suffocation)
13
Q
Streptococcus pneumoniae (Pneumococcus) Secondary Complications
Bacteremia:
Acute Purulent Meningitis:
Pneumococci adhere to:
Pneumococci breach:
A
Bacteremia: due to inflammatory response and damage to endothelial cells
Acute Purulent Meningitis: bacteremia may lead to meningitis
- Pneumococci adhere to vascular endothelium in CNS and cause cell death
- Pneumococci breach BBB/BCB to enter CSF
.
14
Q
Streptococcus pneumoniae (Pneumococcus)
Sputum Gram Stain:
Major Problem:
A
Sputum Gram Stain: important diagnostic tool, but issues
Major Problem: contamination with flora from oropharynx
➢ Sputum is MONOMICROBIC and contains PMNs
➢ Contaminating saliva is POLYMICROBIC and has squamous epithelial cells
15
Q
Streptococcus pneumoniae (Pneumococcus)
G+/-?
Hemolysis:
Lancefield Grouping:
A
- G(+) lancet shaped diplococcic
- Alpha-hemolytic
- No Lancefield grouping
16
Q
Streptococcus pneumoniae (Pneumococcus)
Biochemical Tests: (4)
A
- Capsular serotyping
- Quelling reaction (anti-capsule Abs)
- Optochin (P disk) sensitive
- Bile soluble (distinguish from viridians strep
17
Q
Streptococcus pneumoniae (Pneumococcus)
Blood Culture:
A
- Detects bacteremia and confirms sputum sample
* Latex agglutination used to detect circulating pneumococcal Abs
18
Q
Streptococcus pneumoniae (Pneumococcus)
Radiology:
A
o Radiology: shows bronchopneumonia that can consolidate to lobar pneumonia
19
Q
Haemophilus influenzae Virulence Factors (Relevant to Lower Respiratory Tract Infections):
A
Polysaccharide capsule
• Anti-phagocytic
• Subject to Ag variation
• Hib most virulent (capsular serotype B)
20
Q
Haemophilus influenzae
Normal Flora:
Transmission:
Peak Age Group:
A
o Normal Flora: commonly in upper respiratory tract
• Humans can be carriers of both encapsulated and non-encapsulated (non-typable) strains
o Transmission: person to person (droplet)
o Peak Age Group: 2-5 years old
21
Q
Haemophilus influenzae
Pneumonia: can be caused by both encapsulated and non-encapsulated strains
Encapsulated:
Hib pneumonia:
A
Encapsulated: similar disease to pneumococcal pneumonia
- Hib pneumonia: increased virulence with a higher incidence of positive blood cultures (less common than non-typable because lower colonization rates)
22
Q
Haemophilus influenzae
Pneumonia: can be caused by both encapsulated and non-encapsulated strains
Non-Encapsulated:
A
• Non-Encapsulated: less virulent
23
Q
Haemophilus influenzae
Predisposing Factors of Nontypable Pneumonia: (3)
A
o Chronic bronchitis
o Emphysema
o Obstructive pulmonary disease
24
Q
Haemophilus influenzae
Acute Epiglotittitis:
A
Acute Epiglotittitis: can also be caused by H.influenzae
25
Haemophilus influenzae
Sample Collection:
Cultures:
Sputum and blood cultures (positive in 10-15% of patients; higher with Hib pneumonia)
Cultures:
• G(-) coccobacilli
• Fastidious (requires X and V blood factors for growth)
26
Legionella pneumophilia
| Etiology:
Parasite of freshwater and soil protozoa: Acanthomoeba, Naeglaria
Found in reservoirs for ameba/bacteria (cooling towers, AC systems, plumbing, hospital respiratory equipment); routine disinfection of cooling systems used as prevention
Existence inside ameba provides survival advantage
➢ More resistant to disinfectants
➢ Can survive over winter inside cyst of ameba
➢ May be capable of living outside of ameba in biofilms
27
Legionella pneumophilia
| Transmission:
Transmission: inhalation (but NO person-to-person spread)
28
Legionella pneumophilia
Acute Pneumonia
virulence in humans:
Contributors to pathogenesis:
* Generally low virulence in humans: most people have Abs because of it ubiquity in nature
* Contributors to pathogenesis: nosocomial infections, immunocompromise, smoking, excessive alcohol use, old age
29
Legionella pneumophilia
Legionnaire’s Disease:
Legionnaire’s Disease: severe pneumonia with a 2-10 day incubation period (high mortality rate, especially in immunocompromise)
30
Legionella pneumophilia
| Pontiac Fever:
Pontiac Fever: nonpneumonic (no pneumonia) febrile illness with a 1-2 day incubation period (self-limiting); may be immune response to inhalation of dead/low virulence strains
31
Legionella pneumophilia
| Disseminated Disease:
Disseminated Disease: very rare; usually presents with pneumonia after a long incubation period (days-weeks)
32
Legionella pneumophilia
Disease Process
Inhaled organism has tropism for:
Has a surface protein that binds:
Inhaled organism has tropism for lung alveoli and bronchioles (forms microabsecesses)
Has a surface protein that binds C3 (enhances its own phagocytosis)
➢ “Coiling” phagocytosis
➢ Uptake may also occur without opsonization (bacteria-induced phagocytosis)
33
Legionella pneumophilia
Disease Process
Survives in monocytes/macrophages as:
Once in the cell, expresses 30 new proteins that:
Multiplication of Legionella is normally inhibited in:
• Survives in monocytes/macrophages as intracellular parasite
• Once in the cell, expresses 30 new proteins that:
➢ Prevent phagolysosome fusion and acidification of the endocytotic vesicle
➢ Induce accumulation of ribosomes and mitochondria around phagosome
➢ Facilitate scavenging of iron from transferrin
• Multiplication of Legionella is normally inhibited in an activated macrophage
34
Legionella pneumophilia
Clinical ID
Urine EIA test for:
Normal staining and culture techniques:
Gram Stain:
Growth media:
Urine EIA test for soluble Ag
Normal staining and culture techniques not useful:
Does not Gram stain well:
➢ May be visualized with simple stains devoid of decolorization or silver impregnation
➢ Appears thin, pleomorphic G(-) rod with filamentous forms also seen
Growth media:
➢ Requires amino acids L-cysteine, and ferric ions
➢ Also needs to be on buffered medium (pH restrictions)
➢ Slow growth (2-5 days)
35
Legionella pneumophilia
Clinical ID
Microscopic exam of tissue required:
Legionella should be suspected in cases of:
Organism is rarely found in:
Identification based on:
Microscopic exam of tissue required: since Gram stain not useful
Legionella should be suspected in cases of severe progressive pneumonia with no known etiologic agent
Organism is rarely found in sputum
➢ Need to collect lung aspirate, transtracheal aspirate, or lung biopsy
Identification based on antigenic structure and DNA homology tests
➢ Indirect immunofluorescence of serum (rise in Ab titer to Legionella)
➢ Difficult to assess due to high exposure rates in population
36
Legionella pneumophilia
Clinical ID
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PCR:
Serological Diagnosis (Summary Chart):
```
o PCR: used by reference lab for identification (most human infections caused by Philadelphia strain)
o Serological Diagnosis (Summary Chart): immunofluorescence
37
Acinetobacter spp.
Etiology
Environment:
Antibiotic resistant:
Frequent cause of:
Etiology
o Environment: lives in soil, water and on the skin of healthy people (especially healthcare workers); can survive on dry surfaces for up to 20 days
o Antibiotic resistant: innately resistant to man classes of antibiotics
o Frequent cause of nosocomial infections
38
Acinetobacter spp.
Pathogenesis:
Clinical ID:
- Pathogenesis: causes pneumonia and serious blood/wound infections in immunocompromised patients
- Clinical ID: G(-) coccobacillus (resembles Haemophilus)
39
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Mycoplasma pneumoniae
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Adhesin:
Hydrogen peroxide:
Adhesin: binds sialic acid containing glycolupids or glycoproteins on bronchial epithelial cells
Hydrogen peroxide: damages tissue
40
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Mycoplasma pneumoniae
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Superoxide:
Autoantibodies may be generated during infection:
Superoxide: damages tissue
Autoantibodies may be generated during infection: homology between host cell and mycoplasma membrane glycolipids; reactive to lymphocytes, smooth muscle, brain, lung tissue
41
Mycoplasma pneumoniae
Common age group:
Transmission:
o Common age group: teenagers
o Transmission: droplet spread (very low infectious dose); common in closed communities
• Organism shed both before and long after onset of symptoms
42
Mycoplasma pneumoniae
Pathogenesis
Walking Pneumonia:
Disease Process:
o Walking Pneumonia: less severe than other bacterial pneumonias
o Disease Process:
• Colonization of bronchial epithelium interferes with ciliary action
• Inflammation and exudate are the primary contributors to pathogenesis
43
Mycoplasma pneumoniae
Pathogenesis
Second Infection Site:
Second Infection Site: non-purulent otitis media
44
Mycoplasma pneumoniae
Sequelae
Immunopathology due to:
Possible complications: (3)
Immunopathology due to cross-reactive Abs
Possible complications:
➢ Hemolytic anemia
➢ Aseptic meningitis
➢ Pancreatitis
45
Mycoplasma pneumoniae
Culture
sputum:
culture:
Gram stain:
microscopically:
* No organism in sputum
* Organism grows too slow to culture (require cholesterol for growth)
* No Gram stain (no cell wall)
* Difficult to detect microscopically
46
Mycoplasma pneumoniae
Structure:
Serodiagnosis:
Structure:
• Lack cell wall (no Gram stain or treatment with B-lactams); bound by triple membrane containing sterols
Serodiagnosis: can be used to detect circulating Ags or complement-fixing Ab
• Ab to M.pneumoniae is diagnostic (disease has a long IP so patient presents with high titers)
47
Mycoplasma pneumoniae
DNA hybdrization or PCR:
Serological Diagnosis:
o DNA hybdrization or PCR: also being developed for detection
o Serological Diagnosis (Summary Chart): complement fixation or IgM titers (ELISA)
48
Chlamydia pneumoniae
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
Life Cycle: (2)
Life Cycle:
• Elementary Body: infectious stage that carries adhesin for receptor binding (attaches and induces endocytosis into columnar epithelial cells)
• Reticulate Body: replicates once in cell; metabolically active (uses host ATP)
➢ Eventually reorganize and release infectious EB from the cell
49
Chlamydia pneumoniae
Hosts:
It causes:
Humans are only host: ~50% of adults seropositive, but reinfection still occurs
Causes:
• Pharyngitis
• Bronchitis
• Atypical Pneumonia (Walking Pneumonia): in school children and young adults
50
Chlamydia pneumoniae
| Pathogenesis:
Clinical picture resembles M.pneumoniae
51
Chlamydia pneumoniae
Clinical ID
Morphology/Growth:
Detection:
Serological Diagnosis (Summary Chart):
Morphology/Growth:
• G(-) outer membrane, but no cell wall (cannot Gram stain or treat with B-lactams)
• Coccobacillus
• Inclusions are glycogen (-)
Detection:
• Direct immunofluorescent staining of outer membrane proteins
• DNA or RNA detection using probes and PCR
• Inclusions do not contain glycogen
Serological Diagnosis (Summary Chart): immunofluorescence or ELISA
52
Staphylococcus aureus
| Acute pneumonia:
Acute pneumonia: secondary to some other insult to the lung (ie. influenza)
53
Staphylococcus aureus
| Empyema:
Empyema: purulent infection of pleural space (gains access by contiguous spread from infected lung)
54
Staphylococcus aureus
| Lung Abscess:
Lung Abscess: complication of acute or chronic pneumonia (may be caused by aspiration of oral or gastric contents)
55
Staphylococcus aureus
Clinical ID
Samples:
Antibiotic susceptibilities:
Radiology:
Samples: sputum, lung abscess aspirate, blood culture (disseminated infection)
• G(+) cocci in clusters
• Catalase (+)
• Coagulase (+)
Antibiotic susceptibilities required
Radiology: used to diagnose lung absecesses
56
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Mycobacterium tuberculosis
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Mycolic Acid (Cord Factor):
Resistance to:
Promotes (2):
Mycolic Acid (Cord Factor): long chain fatty acid
• Resistance to drying and disinfectants
• Promotes hypersensitivity granuloma
• Promotes inflammatory response (TNF) and damage to lung tissue
57
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Mycobacterium tuberculosis
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Lipoarabinomamman:
Lipoarabinomamman: cell wall glycolipid
• Suppresses T cell proliferation
• Prevents macrophage activation
58
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Mycobacterium tuberculosis
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Sulfolipids (Polyanionic Lipids):
Catalase:
Ammonia Production:
o Sulfolipids (Polyanionic Lipids): inhibits macrophage phagosome-lysosome fusion
o Catalase: degrades hydrogen peroxide
o Ammonia Production: prevents acidification in phagolysosome
59
Mycobacterium tuberculosis
M.tuberculosis:
M.bovis:
M.africanum:
* M.tuberculosis: primary cause of TB
* M.bovis: from infected milk; has been eradicated through pasteurization (rare cause of TB)
* M.africanum: causes TB in Africa
60
Mycobacterium tuberculosis
M.avium complex (avium and intracellulare):
M.leprae:
* M.avium complex (avium and intracellulare): opportunistic pathogens causing TB-like disease; cause disseminated disease in AIDS patients
* M.leprae: causes leprosy (degenerative disease of skin and nerves; rare in US)
61
Mycobacterium tuberculosis
US Infection Points
Incidence is significant amongst:
Outbreaks often occur in:
multi-drug resistant:
Incidence is significant amongst AIDS patients and immigrants
Outbreaks often occur in closed communities (nursing homes, shelters, prisons)
~1% are multi-drug resistant
62
Mycobacterium tuberculosis
Primary Infection:
Gohn (Primary) Complex:
• Primary Infection: unapparent in 95% of cases
| ➢ Gohn (Primary) Complex: lung granuloma (due to DTH reaction) and enlarged LNs
63
Mycobacterium tuberculosis
Progressive Primary TB:
Disseminates:
• Progressive Primary TB: occurs in ~5% of cases of primary TB (infection does not resolve)
➢ Disseminates: bloodborne or miliary TB
64
Mycobacterium tuberculosis
Reactivation TB:
Common Site:
• Reactivation TB: low percentage of cases (risk increases with age, alcoholism, diabetes, decreased immune function)
➢ Common Site: apex of lung (highest oxygen tension- aerobic organism)
65
Mycobacterium tuberculosis
Disseminated TB:
• Disseminated TB: either due to progressive primary TB or reactivation TB
➢ Occurs through lymph or erosion of necrotic tubercle in lung
➢ Results in infection of liver, spleen, kidney, bone or meninges
66
Tuberculin Skin Test
Inject a purified protein derivative (PPD):
DTH Reaction to PPD:
Inject a purified protein derivative (PPD): autolyzed bacteria containing protein, lipid, polysaccharide and nucleic acid injected under the skin and reaction read in 48-72 hours
DTH Reaction to PPD: local induration and erythema is positive reaction (seen 6 weeks after primary infection)
67
Tuberculin Skin Test
Positive DTH Reaction Significance:
Positive DTH Reaction Significance:
➢ Coincides with tubercle (hypersensitivity granuloma) formation
➢ Indicates exposure (to M.tuberculosis or cross-reactive species), but not necessarily active disease (only 5% of skin test positive cases progress to active disease)
➢ BCG vaccination renders test invalid (will always be positive)
68
Tuberculin Skin Test
| Negative DTH Reaction Significance:
Negative DTH Reaction Significance:
➢ No exposure to organisms
➢ In prehypersensitivity stage (within 6 weeks of exposure)
➢ Loss of sensitivity (disappearance of Ag from primary complex)
➢ Anergy due to immunocompromise (poor prognosis if test was previously positive)
69
Mycobacterium tuberculosis
Transmission:
Engulfed by alveolar macrophages:
Resists innate defenses:
Humoral response is weak (IgM):
o Transmission: aerosol inhalation, enters the lungs (primary focus)
o Engulfed by alveolar macrophages: carried to LN
o Resists innate defenses: PMNs, inactivated macrophages, lysozyme
o Humoral response is weak (IgM): no effective complement-mediated killing
70
Mycobacterium tuberculosis
| Cell-Mediated response:
* Helper and cytotoxic T cells activate alveolar macrophages to ingest organisms
* Activated macrophages prevent replication of organism; if there is an inadequate response, the organism can replicate in the macrophage phagosome
* Slow replication (part of pathogenesis)
* Cytokine response to organism causes systemic TB symptoms (weight loss, fever)
71
Mycobacterium tuberculosis
| Containment of pathogen in tubercle (microscopic granuloma):
* Made of multinucleated giant cells, activated macrophages and lymphocytes
* Can become necrotic and caseous (cheesy)
* Fibroblasts and collagen accumulate at lesion
* Tissue destruction causes chronic productive cough and blood-stained sputum
72
Mycobacterium tuberculosis
| Potential fates of tubercle:
* Become fibrotic/calcified with dead bacteria (shows up on chest X-ray)
* Can remain dormant for years (source of reactivation)
* Necrotic tubercles may erode into blood vessels (causing disseminated/miliary TB)
73
Mycobacterium tuberculosis
| DTH reaction confers long-lived memory and protection from re-infection:
* Loss of prior DTH is a bad prognostic indication of rapidly progressing disease (see above)
* Basis of tuberculin skin test
74
Mycobacterium tuberculosis
| Specimen collection:
o Specimen collection: sputum, biopsy (sometimes), blood (if miliary TB)
75
Mycobacterium tuberculosis
| Staining:
o Staining: provides diagnosis BEFORE bacteria grows (slow growing)
• Acid Fast Stain (Ziehl-Neelsen)
• Chemotherapy monitored by periodic examination for AFB counts
76
Mycobacterium tuberculosis
Cultivation
Very slow growth:
Special media:
Very slow growth: decontamination of sputum (4% NaOH) to inhibit faster growing bacteria; appearance of visible colonies may take 2 weeks (24 hour doubling time)
Special media: Lownstein Jensen (LJ) agar or Middlebrook agar
77
Mycobacterium tuberculosis
| Rapid ID: (3)
* rRNA and DNA probes
* PCR to detect common insertion sequence
* Growth in 14C-palmitic acid (catabolized to CO2 which is therefore labeled and measured)
78
Mycobacterium tuberculosis
Drug susceptibilities:
Extensively drug-resistance TB (XDR TB):
Drug susceptibilities: done in reference labs
Extensively drug-resistance TB (XDR TB): rare type of multidrug-resistant TB (MDR TB)
• Resistant to first line and second line drugs
79
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Pseudomonas aeruginosa
Virulence Factors (Relevant to Lower Respiratory Tract Infections): (5)
```
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o Adhesins
o Alginate
o Elastase
o Exotoxin A
o Multiple resistance to antimicrobials and disinfectants
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80
Pseudomonas aeruginosa
| Adhesins:
* Protein pilus adhesin (binding to asialoGM1)
| * Non-pilus adhesin (binding to mucus)
81
Pseudomonas aeruginosa
| Alginate:
Alginate: polysaccharide capsule for biofilm formation
• Permits colonization of lung and evasion of the host immune response
• Regulated in response to environmental signals
82
Pseudomonas aeruginosa
| Elastase:
Elastase: protease that degrades lung elastin (tissue damage)
83
Pseudomonas aeruginosa
| Exotoxin:
Exotoxin A: similar structure/activity to diphtheria toxin (ADP ribosylation of elongation factor 2)
84
Pseudomonas aeruginosa
Multiple resistance to antimicrobials and disinfectants
Mutation leads to:
Alteration of LPS to form that does not bind:
* Mutation leads to loss of porin and decreased entry of antimicrobials
* Alteration of LPS to form that does not bind antibiotics
85
Pseudomonas aeruginosa
| Etiology:
Etiology: common environmental isolate that can cause nosocomial infections (waterborne)
86
Pseudomonas aeruginosa
| Conditions causes: (3)
* Acute pneumonia
* Empyema
* Abscesses
87
Pseudomonas aeruginosa
Infections in Cystic Fibrosis
CF Lung:
Increased susceptibility to infection by Pseudomonas:
CF Lung: increased mucus secretion due to defect in CFTR (causes decreased sialylation of surface glycolipids)
Increased susceptibility to infection by Pseudomonas: because of increase in asialoGM1
88
Pseudomonas aeruginosa
Infections in Cystic Fibrosis
Resistance to phagocytosis:
physical barrier to phagocytosis =
anti-pseudomonas Abs:
Resistance to phagocytosis: Pseudomonas infecting CF lung phenotypically switch to mucoid form
- Alignate gel + excess mucus in CF = physical barrier to phagocytosis
- In addition, anti-pseudomonas Abs may be defective in CF patients
89
Pseudomonas aeruginosa
Infections in Cystic Fibrosis
Resistance to antimicrobials:
Primary infection in younger age group by:
Resistance to antimicrobials: alginate gel + excess mucus in CF = physical barrier to drugs
- Primary infection in younger age group by S.aureus; colonizing Pseudomonas strains develop resistance to anti-staphylococcal drugs used to treat it
90
Pseudomonas aeruginosa
Infections in Cystic Fibrosis
Lung tissue damage:
Infection rarely spreads beyond:
* Lung tissue damage: persistent colonization and elastase release by pathogen results in tissue damage and inflammation (recruited PMNs also release protease that contributes)
* Infection rarely spreads beyond lungs in patients with CF
91
Pseudomonas aeruginosa
G+/-:
Aerobic?
Ox =/-?
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o G(-) rods in sputum
o Aerobic (OF Dextrose tubes demonstrate aerobic growth)
o Oxidase (+)
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92
FUNGI CAUSING LOWER RESPIRATORY TRACT INFECTIONS: (5)
* Aspergillus spp.
* Histoplasma capsulatum
* Blastomyces dermatitidis
* Coccidioides immitis
* Pneumocystis (carinii) jirovecii
93
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Aspergillus spp.
Virulence Factors (Relevant to Lower Respiratory Tract Infections):
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Dimorphic growth:
Infectious conidia:
Hyphae:
Alflatoxin:
NO DIMORPHIC GROWTH PHASE
Infectious conidia: germinate to mold form
Hyphae: bind fibrinogen and complement components
(Alflatoxin: produced by A.flavus growing on peanuts- potent carcinogen)
94
Aspergillus spp.
Basics:
Predisposing Factors: (4)
Basics: common environmental mold that is an emerging etiologic agent of nosocomial pneumonia
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Predisposing Factors:
• Asthma
• Chronic bronchitis
• TB
• Immunosuppression (opportunistic infection)
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95
Aspergillus spp.
| Requirements for infection:
* Frequent inhalation of infectious conidia
| * Inhalation of fungal elements (spores) or colonization (allergic aspergillosis/Farmer’s lung)
96
Aspergillus spp.
| May colonize respiratory tract:
- May lead to tissue invasion by hypae
| - Principal host defense is pulmonary PMN killing of invasive hyphae
97
Aspergillus spp.
| Infections Cause: (2)
* Acute Pneumonia
| * Lung Abscesses
98
Aspergillus spp.
Lung aspiration, bronchial lavage, or biopsy
Mold form:
Structure:
* Mold form: grows rapidly and is easily identified
| * Structure: typical septate hyphae with conidia (spore)
99
Aspergillus spp.
| Radiology:
Radiology: visible fungus ball can form in pulmonary cavity
100
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Histoplasma capsulatum
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Dimporphic Growth Phase:
Dimporphic Growth Phase: mold in environment that produces infectious conidia; pathogenic yeast in tissue
101
Histoplasma capsulatum
Environmental source:
Transmission:
Environmental source: associated with bird and bat droppings
Transmission: inhalation of conidia (exposure is common, but disease is rare); no person to person transmission
102
Histoplasma capsulatum
Primary infection site:
Causes a chronic pneumonia:
Immune response:
o Primary infection site: pulmonary
o Causes a chronic pneumonia: grows inside macrophages and produces a granuloma similar to TB; may disseminate to infect organs of the reticuloendothelial system
o Immune response: T cell activation of macrophages to prevent intracellular growth (long term immunity to re-infection)
103
Histoplasma capsulatum
Clinical ID
Radiograph:
Blood or biopsy required:
If disseminated infection:
Isolation of yeast cells:
* Radiograph: granulomas resembling TB
* Blood or biopsy required: sputum not useful
* If disseminated infection: biopsy of liver, spleen, and LN
* Isolation of yeast cells: in bone marrow
104
Histoplasma capsulatum
Clinical ID
Cultural isolation/histological identification (firm diagnosis):
* Grows slowly on BAP and Sabouraud agar
* Fungus appears dimorphic (yeast and mold forms)
* Mold form produces tuberculate macroconidia (finger-like projections carrying spores)
105
Histoplasma capsulatum
Clinical ID
Serological Tests:
* There is widespread exposure and cross-reactivity to other pathogens
* DTH skin reaction to mycelial Ag used for epidemiological analyses
* Complement fixing Ab test for yeast and mycelial Ags predicts prognosis
106
Histoplasma capsulatum
Clinical ID
2 other tests:
o Immunodiffusion test
| o DNA probe
107
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Blastomyces dermatitidis
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Similar to Histoplasma:
Difference:
Similar to Histoplasma: dimorphic growth phase
Difference: yeast cells exist extracellularly, not in macrophages
108
Blastomyces dermatitidis
Geographic distribution:
More common in:
Geographic distribution: similar to Histoplasma (middle and SE US)
More common in males: probably due to occupational exposure
109
Blastomyces dermatitidis
Conidia inhaled from:
PMN infiltration:
May mimic:
Conidia inhaled from soil: results in pulmonary infection with yeast cells
PMN infiltration: and formation of granuloma, leading to chronic pneumonia
- May mimic pulmonary tumor or TB
110
Blastomyces dermatitidis
May disseminate
Chronic infection of _____ most common
Chronic infection of skin and bone most common
- May even disseminate in subclinical infections
- Necrosis and fibrosis at infected area can lead to disfigurement
Dissemination to UG tract also possible
111
Blastomyces dermatitidis
| Immune response
T cell mediated response and cytokine-activated macrophages
Large yeast cells can resist oxidative and non-oxidative killing mechanisms
112
Blastomyces dermatitidis
| Clinical ID: (3)
Biopsy:
• Large yeast cells with broad buds
• Grows slowly on mycological media (~4 weeks)
Serodiagnosis: hampered by cross-reactivity with other fungi
No skin test
113
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Coccidioides immitis
Virulence Factors (Relevant to Lower Respiratory Tract Infections)
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Dimorphic growth phase:
Mold:
Spherule:
Dimorphic growth phase
• Mold: produces infectious arthroconidia
• Spherule: invasive tissue form that produces reproductive endospores
114
Coccidioides immitis
| Geographical:
Geographical: Southwestern US (Valley Fever)
115
Coccidioides immitis
Usually mild disease:
May become chronic pneumonia:
May disseminate to:
Usually mild disease: Valley fever is acute pulmonary infection with cough, chest pain, and myalgia
May become chronic pneumonia: occurs with decreased T cell response (AIDS, chemo)
May disseminate: to skin, bone, joints and meninges (very rare)
116
Coccidioides immitis
Disease Process
Arthroconidia ____ and converts to _____
PMNs and macrophages respond:
Release of endospores from spherules induces a strong inflammatory response:
Inflammatory response results in:
Arthroconidia inhaled and converts to spherule
PMNs and macrophages respond
- Arthroconidia phagocytosed
- Spherule grows too large for phagocytosis
Release of endospores from spherules induces a strong inflammatory response
- Endospores phagocytosed
- Intracellular forms can prevent phagolysosome fusion and survive
Inflammatory response results in granuloma formation (15% cavitate)
117
Coccidioides immitis
| Immune Response:
Cell mediated (PMN, T Cell) immunity to arhtoconidia or endospores
Chronic or progressive infection can result in T cell anergy
- Spherules burst and pathogen load is so heavy it induces anergy)
118
Coccidioides immitis
Clinical ID
Best:
Best: detection of characteristic spherules in histologic sections
119
Coccidioides immitis
Clinical ID
Detection of complement fixing Abs indicates prognosis
Low titers:
High titers:
Low titers: primary pulmonary disease with good CMI response
High titers: disseminated disease and T cell anergy
120
Coccidioides immitis
Clinical ID
Skin test detects DTH, but is of limited value:
Positive:
Negative:
2 others:
Skin test detects DTH, but is of limited value: due to common exposure
• Positive: 1-4 weeks after onset and positive for life (indicates immunity to reinfection)
• Negative: may be performing too soon after exposure or disease has progressed to anergy
Immunodiffusion
DNA probe
121
Pneumocystis (carinii) jirovecii
| Etiology:
Very common infection of generally low virulence
122
Pneumocystis (carinii) jirovecii
| Causes PCP in immunocompromised hosts: (4)
* Premature infants
* Patients undergoing chemotherapy
* Organ transplant patients on immunosuppressants
* AIDS (primary predisposing factor)
123
Pneumocystis (carinii) jirovecii
| Presenting Manifestation of AIDS: (3)
* Most common opportunistic infection in AIDS
* Prophylaxis and HAART has reduced incidence
* Occurs due to loss of T cell function (risk increases when T cell count below 200)
124
Pneumocystis (carinii) jirovecii
Acute Pneumonia/Lethal Pneumonitis
Progressive, diffuse pneumonia after:
Concurrent infections:
Alveoli become filled with:
Progressive, diffuse pneumonia after:
➢ Corticosteroid use and leukemia
➢ AIDS onset (insidious onset; lesions outside of lung may also be seen)
Concurrent infections common (bacterial, fungal, parasitic, viral)
Alveoli become filled with desquamated cells, organisms, monocytes and fluid (foamy appearance)
125
Pneumocystis (carinii) jirovecii
Clinical ID
Classification
Classified as a _____ based on morphology and drug susceptibility
Classified as a _____ based on rRNA sequence homology with other fungi
Classified as a protozoan based on morphology and drug susceptibility
Classified as a fungus based on rRNA sequence homology with other fungi
126
Pneumocystis (carinii) jirovecii
Clinical ID
Sputum induced with:
What are more helpful?
Sputum induced with hypertonic saline (only usefully in AIDS patients because of larger number of organisms)
Brochoalveolar lavage and transbronchial biopsies more helpful
127
Pneumocystis (carinii) jirovecii
Clinical ID
Histological:
1 other method of clinical ID:
Histological (Definitive):
• Extracellular cysts and trophs seen
• Latent infections characterized by scattered cysts in contact with alveolar cells
PCR
128
Pneumocystis (carinii) jirovecii
Based on Symptoms: (5)
* Mild or low grade fever
* Typical signs of pneumonia absent (cough is non-productive)
* Progressive dyspnea and tachypnea
* Cyanosis and hypoxia
* Death by asphyxiation
