Pulmonary Pathogens Flashcards
(77 cards)
1
Q
Streptococcus pneumoniae characteristics (shape, gram, hemolysis)
A
Diplococcus
Gram+
Lancet-shaped coccus
Pairs or short chains
Alpha-hemolytic (green hemolysis- incomplete)
Carbohydrate capsule (>90 serotypes)
Naturally competent for DNA transformation (can take up DNA from environment/plasmids, makes it more pathogenic)
2
Q
Streptococci
A
Gram+ Chains Normal flora of skin and mouth Facultative anaerobes Catalase negative Non-motile, non-spore forming Exotoxins
3
Q
Beta-hemolytic Streptococci
A
Group A Streptococci: GAS; S. pyogenes
Strep throat
Group B Streptococci: GBS; S. agalactiae
Neonatal infections, bacteremia
4
Q
Alpha-hemolytic Streptococci (incomplete lysis of RBCs)
A
“Viridans streptococci”; S mutans; dental carries, endocarditis
Streptococcus pneumoniae: Pneumonia, otitis, meningitis
5
Q
Gamma-hemolytic Streptococci
A
Enterococcus
6
Q
Host of S.p., carriage, colonization rate, transmission, higher cases in what population
A
- Human to human (humans are only host)
- Asymptomatic nasopharyngeal carriage common (5-75% of population; considered commensal)
- Colonization rate highest in children
- Transmission via respiratory droplets
Most cases spread from endogenous organisms - Bacteremia and invasive disease higher in AA and Native Am
7
Q
What is the most common cause of Community-Acquired Pneumonia? (CAP) What’s it’s mortality?
A
Streptococcus pneumoniae
Mortality 5-10% after antibiotic, 20-30% pre-antibiotic
Moraxella also causes CAP
8
Q
Streptococcus pneumoniae can develop into what? What is a predisposing factor?
A
Sinusitis
Otitis media
Meningitis (children, 25-100% fatal) - major complication
Predisposing factor is a respiratory viral infection (like influenza)
9
Q
Clinical Presentation of Pneumonia (incubation, onset, production, location, risk factors)
A
- Aspiration of bacteria and replication in alveolar spaces
- 1-30 day incubation period
- Abrupt onset of fever and shaking chills
- Pleurisy, productive cough, blood tinged sputum
- Localized to lower lobes of lungs
- Bacteremia occurs in 25-30% of patients
- Risk factors include: antecedent resp. viral infection, smoking, age <2 or >65, hematological disorders (asplenia, chronic pulmonary disease, diabetes, renal disease)
10
Q
Atypical “Walking Pneumonia (Symptoms and pathogens/differential)
A
Slow onset
Moderate fever
Non-productive cough
Headache
Chlamydia pneumoniae Legionella pneumoniae Mycoplasma pneumoniae Chlamydia psittaci Coxiella burnetii Viruses
11
Q
Meningitis
A
Manifestation of S.p., mainly pediatric
100% mortality without antibiotic, 25% with antibiotic
Inflammation leads to brain damage, blindness, hearing loss, learning disabilities
12
Q
Otitis media and sinusitis
A
Manifestations of S.p., mainly pediatric
~50% of middle ear infections
Sinusitis occurs in all age groups
Can develop into meningitis
13
Q
S.p. Virulence factors (capsule, PS)
A
- Polysaccharide Capsule
90 serotypes (makes vaccination an issue)
Essential for pathogenesis
Immunogenic (responses are directed at capsule)
Anti-phagocytic - C polysaccharide
Complex of phosphorylcholine, peptidoglycan, teichoic acid
Common to all S.p. serotypes
PResent in urine and serum during infection
14
Q
S.p. Toxins (3)
A
- Pneumolysin (released once cell is lysed)
Cholesterol-dependent, pore-forming toxin
Targets bronchial epithelial cells
Activates classical complement pathway - Autolysin (in cell wall, self-lysin)
Binds to cell wall via phosphorylcholine
Degrades peptidoglycan, resulting in bacteria cell wall lysis
Releases pneumolysin from inside cell
Releases cell wall components (peptidolgycan, teichoic acids) that activate inflammatory response
Antibodies to autolysin can be protective
Involved in generation of C polysaccharide - IgA protease
Secreted antibody that lines the wall of bronchus, prepares a niche for itself; blunts mucosal adaptive immune response
15
Q
Lab diagnosis of S.p. (shape, hemolysis, culture 3)
A
Lancet-shaped Gram+ diplococci
Narrow zone of hemolysis on sheep blood agar (5-15% can be nonhemolytic)
Culture: 1. Bile soluble 2. Optochin-sensitive: KB testing; disk; S.p. is sensitive, see a zone of inhibition 3. Quellung "swelling" Reaction with specific antisera Visualizes capsule Makes bacteria look bigger
16
Q
Lab diagnosis of S.p. in bodily fluids (CSF, Urine)
A
C polysaccharide in urine and serum
Capsular antigen detected in CSF with latex agglutination assay
Urine antigen assay: approved by FDA to detect S. pneumoniae
17
Q
Treatment of S.p. (susceptibility, resistance, DOC)
A
- Isolates have increased MIC to penicillin (increasingly resistant)
Susceptible: MIC <2mg/mL, 8mg/mL, >2mg/mL for meningeal isolates
Much lower for meningeal because having a hard time actually getting penicillin into meninges to actually treat patients with it - Isolates also may be resistant to macrolides and to Bactrim
- Most are susceptible to fluoroquinolones
DOC: Penicillin (for sensitive isolates); vancomycin or fluoroquinolone + 3rd gen. cephalosporin
18
Q
Pneumovax
A
Pneumococcal Polysaccharide Vaccine (PPSv23)
Covers most bacteremic strains of pneumococcus (23 strains)
Capsular type-specific antibody is protective
Recommended for:
Adults >65
Chronically ill
Immunocompromised children >2
Increases antibody titers for up to 5 years
19
Q
Prevnar
A
Pneumococcal Conjugate Vaccine PCV7
Capsular antigens from 7 serotypes conjugated to a mutated diphtheria toxin
Immunogenic in infants and children
Recommended for all children <2 years and at risk children <6 years
20
Q
Prevnar13
A
PCV13
Capsular antigens from 13 serotypes conjugated to a mutated diphtheria toxin
FDA-approved (Jan 2013) for children 6-17years and adults >50 years
21
Q
Legionella pneumophila (origin, hospitalizations, shape, characteristics, environment)
A
Potentially severe form of pneumonia
About 10,000 hospitalizations a year
1976 outbreak at Am Legion convention
Large genus with multiple pathogens
80-90% of Legionella infections
Gram- bacillus/coccobacillus
Does NOT stain well
Motile/catalase positive
Facultative intracellular bacterium, can grow in amoeba
Fastidious (difficult to grow, needs lots of nutrients)
L-cysteine (legionella is an auxotroph)
Ferric ions
pH 6.9 (close to neutral)
22
Q
Legionella epidemiology (transmission, location, common sources, outbreaks, risk factors)
A
- Transmission via inhalation of aerosols
No person-person transmission (env. pathogen that gets into lungs by mistake) - Located in fresh water and soil
Intracellular symbionts of amoebae (lives inside cells, access to nutrients) - Sources: Air conditioning, cooling towers, showers, whirlpools, humidifiers, medical resp. equipment
- Outbreaks late summer-fall, large buildings
5. Risk factors: Increased age Smoking Heavy alcohol use Transplant recipients Immunocompromised patients (diGeorge)
23
Q
Facultative Intracellular Legionella (what does it infect, how does it replicate, what does it produce 2)
A
- Infects alveolar macrophages
MOMP adhesin uses C3 complement to stimulate uptake by macrophage - Bacterial replication in phagosomes
T4SS effectors block acidification/fusion with lysosomes
“Replicative vacuoles” surrounded by ER - Make hemolysin
Tissue degradation
Lysis of RBC - Makes phospholipases
For vacuolar escape (break out and affect other cells)
Surfactant degradation
24
Q
Legionellosis - Clinical Disease (Features, Radio, Incubation, Attack Rate, Isolation, Outcome)
Legionnaire’s Disease
A
1. Symptoms: Non-productive cough GI symptoms (diarrhea, ab pain, nausea) Headache Moderate fever Fatigue Anorexia Hyponatremia Chest pain
- Radiograph pneumonia - yes
- Incubation 2-14 days (late summer-fall)
- Attack rate <5%
- Isolation of organism is possible
- Hospitalization is common, case fatality is 5-40%
15-20% mortality (sporadic disease is frequently misdiagnosed)
25
Pontiac Fever (Features, Radio, Incubation, Attack Rate, Isolation, Outcome)
Another manifestation of Legionella infection
1. Flu-like illness (malaise, fever, chills) without pneumonia (self-limiting)
2. No radiograph
3. Incubation 24-48 hours (year round)
4. 90% attack rate (percentage who get sick when they're exposed to pathogen)
5. Never isolate organism
6. Hospitalization is uncommon, fatality 0%
26
Lab Diagnosis of Legionella (4)
1. Sputum or tracheal aspirates:
DFA (gram stain insensitive, so replaced by this more sensitive alternative)
Dieterle's silver stain
2. Paired serology:
Presumptive: IgG, IgM titer >= 1:128
Definitive: IgG, IgM titer >256 or 4 fold increase in convalescent serum
Gold standards:
3. Culture:
Growth on BCYE (buffered charcoal yeast extract) agar only; provides legionella the 6.9pH required for growth
4. Legionella urine antigen:
Detects only serotype 1 L. pneumophila (majority of infections)
27
Legionella Treatment and Prevention (activity, antibiotics, source, temperature and treatment of water)
B-lactamase activity common
Antibiotics:
1. IV Fluoroquinolones (levofloxacin, moxifloxacin)
2. IV Azithromycin
Both can easily enter eukaryotic cells (since Legionella is facultative intracellular)
Identification of source organism
Water:
1. Increase temp to 70-80 C
2. Hyperchlorination
3. Removal of scale from water storage tanks
4. Routine monitoring of hospital water supply
28
Mycoplasma (found, size, growth, structure)
1. Extracellular parasite of human mucosal surfaces
```
2. Small:
Smallest free living organism
Smallest genome
Tissue culture contaminant
(really dependent on host for nutrients)
```
3. Slow growth (1-6 hours generation time)
4. Lack cell walls
Cell membranes contain sterols
Pleomorphic, asymmetric morphology (change size and shape)
Therefore, no:
peptidoglycan
Teichoic acid (found in cell wall- specific to GP bacteria)
LPS (specific to GN bacteria)
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Pathogenic Mycoplasma (4)
```
1. M. pneumoniae
Atypical walking pneumonia
Tracheobronchitis
Mild upper respiratory infections
Joint infections
```
2. M. hominis
Post partum fever, uterine infections, joint infections
3. M. genitalium, Ureaplasma urealyticum
Non-gonococcal urethritis
4. M. fermentans, M. penetrans
Disseminated infections in AIDS patients
30
M. pneumoniae cell shape
Cytadhesin organelle (arrow)
Penetrates membrane and binds resp. epithelial cells
31
M. pneumoniae epidemiology (spread, incubation, infection, cases/yr, people at risk)
1. Spread through respiratory secretions
2. Incubation time 1-3 weeks
3. Infection rate highest under crowded conditions
4. >20m cases/yr (mostly mild)
5. Older children, adolescents, young adults, HIV patients most susceptible
32
Tracheobronchitis and Pneumonia (pathway)
1. Binding of ciliated respiratory epithelial cells
2. Production of phospholipases and peroxides
3. Ciliostasis, leakage of epithelial cells
4. Infection of lower resp. tract
5. IL-1, TNF-a
6. Influx of PMNs, T and B cells
33
M. pneumoniae Pneumonia (symptoms, CBC, radio, resolution)
1. Headache, fever, pharyngitis
Dry, nonproductive cough
2. No elevation of WBCs
3. Chest radiography
Bilateral, diffuse infiltrates
Lobar pneumonia
4. Skin rash (Stevens-Johnson syndrome: erythema multiforme)
5. Typically resolves 4-6weeks (self limiting)
34
M. pneumoniae Culture (medium, colonies and inhibition)
1. Medium most contain cholesterol or serum (for growth, to stabilize membrane because no cell wall)
2. Add B-lactam to inhibit growth of other organisms
Colony formation in 2-6 weeks
3. Mulberry colony formation
Other Mycoplasmas grow fried-egg colonies
35
M. pneumoniae Serology (4)
1. Cold aggultinin assay
Agglutinating titer >1:64 or increasing titer
Positive 50-65% of patients
2. Complement fixation assay
M. pneumoniae antibodies peak 4 weeks after infection
Titer >1:32 diagnostic
Low specificity but positive in 90% of confirmed cases
3. ELISA for IgM/IgG
4. GO TO: PCR nucleic acid
36
Mycoplasma Treatment (resistance, DOC)
Resistant to:
1. Penicillins
2. Cephalosporins
3. Glycopeptide antibiotics
```
DOC:
1. Tetracyclines
2. Macrolides (Azithromycin)
Macrolide resistance on the rise
3. Fluoroquinolones (Levofloxacin)
```
All targeting protein synthesis (ribosome) or DNA replication (replication machinery like topisomerase)
Not cell wall destruction because no cell wall!
37
Paramyxoviruses
Enveloped, pleomorphic virions
Contain non-segmented negative ssRNA
All induce syncytia (multinucleated cells)
(so do VZV, HSV)
Disruption of the virus releases helical nucleocapsid
38
Paramyxoviridae Structure
All paramyxoviruses have F fusion protein (responsible for forming syncytia)
Attachment proteins differ between viruses (spikes)
Parainfluenza and mumps: HN protein (hemagglutinin)
Measles: H glycoprotein
RSV: G glycoprotein
39
Replication of Paramyxoviruses
1. Fusion into host cell at membrane
2. Must be turned into +ssRNA to serve as mRNA
3. Then turned back into -ssRNA to serve as viral genome for emerging viruses
40
Respiratory Syncytial Virus (RSV) (strains, risk groups)
Considerable strain variation
A and B subgroups by monoclonal sera
Both subgroups circulate simultaneously in population
Epidemics occur in winter
```
Risk groups:
#1 cause of bronchiolitis and pneumonia in children <1 in US
High risk: congenital heart disease, bronchopulmonary dysplasia, immunodeficiency
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Significant cause of respiratory disease in older adults
High risk: Stem cell transplants, severe heart disease, COPD
41
RSV symptoms
```
Fever, chills
Cough, congestion, rhinorrhea (nasal cavity filled with fluid), conjuctivititis, coryza (stuffy nose, inflammation of membrane)
Bronchiolitis: wheezing, SOB
Pneumonia
Apnea spells in infants
```
42
RSV Lab diagnosis
RADT (rapid antigen detection test) from nasoph. aspirates
```
Take swab
Suspend antigens in liquid
Extract liquid
Put on stick like preg. test
Antigen diffuse with other carriers
Captured by antibodies on script
Lead to presentation of antigens at position of antibodies
Test and controlled test will have to be positive in order to be scored
```
RT-PCR from bronchial washes
Fast, sensitive, specific
Culture too slow to be clinically relevant
Serology: retrospective diagnosis
43
RSV Treatment and Prevention (SC, AR, HMA)
Supportive care:
Fluid management
Resp. support: nasal suctioning, O2, positive pressure ventilation, intubation if needed to facilitate O2
XX glucocorticoids, bronchodilators (NOT effective)
Aerosolised ribavirin:
Severly immunocompromised pediatric and adult patients with severe disease
Stem cell transplant patients with upper resp. disease and RISK for progression to lower resp. tract disease
Human monoclonal antibodies:
Used to protect at-risk infants (premature, congenital heart/chronic pulmonary disease)
Not helpful after infection
No vaccine
44
```
Human Metapneumovirus (hMPV)
Isolation, distribution, circulation, seropositivity, causes, symptoms, treatment
```
Close relative of RSV
First isolated in 2001
Worldwide distribution
Circulated for at least 50 years
Causes 5-20% of pediatric URI and LRTIs
Seropositivity: 90% at 5 y.o.
100% in adults
(many have seen virus and are immune resistant. mainly an issue in little kids)
Clinically indistinguishable from RSV
Supportive treatment
45
Parainfluenza virus (family, serotypes)
Paramyxoviridae family
-ssRNA enveloped
```
Five serotypes (1,2,3,4a,4b)
Reinfection is common because serotypes are different enough
```
46
Parainfluenza virus pathogenesis (manifestation, causing, driven by, severe disease, mortality)
Large airways of LRT
Tropism for ciliated epithelial cells
Croup, bronchiolitis, can cause pneumonia
Illness driven by immune response:
Humoral: neutralizing antibody to surface proteins; mucosal IgA can help prevent infection
Cellular: cytotoxic T cells
Severe disease in both adult and pediatric hematopoietic stem cell transplants (HSCT) and in solid organ transplant recipients
Mortality rate up to 37% with pneumonia
47
Parainfluenza virus Prevention and Therapy (croup, immunocomp, investigational)
Hand hygiene
Croup: supportive care
Immunocompromised/transplant patients: reduce immunosuppresion- mainly steroids
Investigational:
Bacterial sialidase fused to respiratory epithelium-anchoring domain
Cleaves sialic acids from receptors and reduces viral entry
Used in lung transplant and stem cell patients
H-N inhibitors
Human PIV immunoglobulin
No vaccine
48
Crackles (Rales) [auscultate, timing, cause, description]
Auscultate: over lung field and airways; heard commonly in bases of lower lung lobes
Timing: more obvious during inspiration
Cause: Air passing through mucus or fluid in any air passage
Description: light crackling, bubbling, high-pitched
Often seen with patients that have effusion from heart failure or infectious etiology. Can be appreciated with infiltrates.
49
Gurgles (Rhonchi) [auscultate, timing, cause, description]
Over larger airways
More pronounced during expiration
Airways narrowed by bronchospasm or secretions
Coarse rattling, gurgling, harsh, moaning or snoring quality
May be cleared by cough
Seen with productive cough in diseases like cystic fibrosis, COPD exacerbation, pneumonia
50
Wheezes [auscultate, timing, cause, description]
Overall lung fields and airways
Inspiration or expiration
Air passing through narrowed airways
Creaking, whistling, high-pitched, musical squeaks
Found in COPD and asthma, with benign x-ray findings
51
Blood Gas
Want arterial blood gas (from wrist)
Venous will be more acidodic because more CO2
PO2 will be really low and won't give you good correlation to arterial Co2
52
Respiratory Alkalosis
Blowing off Co2
Becoming more alkalotic (pH increasing)
Tachypnea
53
Respiratory Acidosis
Holding onto CO2
| Becoming more acidodic
54
CURB65
```
Confusion
Urea >20mg/dL (renal failure- severe sepsis)
RR >30
BP <90 or <=60
age >65
```
0-1 outpt
1-2 inpt
>3 ICU
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HAP
Pneumonia occurring 48hours or longer after admission
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VAP
Pneumonia occurring 48hrs or longer after ventilation
57
HCAP
Associated with increased risk for multi drug resistant pathogens
Must have visited or been admitted to a hospital, LT care facility, or dialysis center within past 90 days
Pneumonia associated with exposure to HC settings
Ex. MRSA
58
Aspiration pneumonia or chemical pneumonitis (most common)
Aspiration of toxic substance into lungs
Most common substance is gastric contents
59
The most common cause of pneumonia
Streptococcus pnemuoniae
60
Common and uncommon causes of pneumonia in pulmonary co-morbid patients (bird owners, HIV/AIDS)
Common in pulmonary co-morbid patients:
Staphylococcus aureus
Enterobacteriaceae
Pseudomonas aeruginosa
```
Atypical:
M. pneumoniae
Legionella spp. (1-9% of CAP cases, usually sporadic)
C. pneumoniae
C. Psittaci (bird owners)
Pneumocystis jirovecii (HIV/AIDS)
M. tuberculosis
```
Viruses
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Drug resistance
1. Change ribosomal target so antibiotic can't bind where it normally does
2. Prevent entry
3. Efflux pump
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Outpt treatment (no co morbid, co morbid)
No co-morbidities and no prior antibiotic use:
Macrolide (azithromycin) unless areas of high macrolide resistance then use doxycycline
Co-morbidities or prior antibiotic use:
Fluoroquinolone (Ciprofloxacin, levofloxacin)
63
Inpt treatment
IV or PO levofloxacin
IV cefriaxone and azithromycin
IV in case of vomiting, nausea
64
Healthcare associated pneumonia
Concern is risk for more resistant pathogens (MRSA)
```
Risk factors:
septic shock
Ventilator support
IV antibiotics in last 90 days
Structural pulm disease (cystic fibrosis, sputum culture with GN bacilli -pseudomonas)
```
65
MRSA
Methicillin resistant Staph aureus
PBP2a, penicillin binding protein encoded by MecA gene that allows organism to grow and divide in presence of methicillin and other B-lactam products
(alters penicillin binding site on staph and prevents other penicillins and B-lactam units from binding)
Changes the affinity of methicillin to this binding site
MecA gene located on mobile gene element called SCCmec
More common in patients who are post-influenza positive
66
Treatment for MRSA
Vancomycin
1+ risk factors: cover MRSA, GN bacilli, MDR Pseudomonas
Piperacillin-tazobactam (b lactam), antipsudomonal fluoroquinolone, linezolid or vancomycin
67
VAP
Piperacillin-tazobactam, levofloxacin, carbapenems, cefepime (4th gen cephalosporin)
```
Biggest issue is prevention
Keep head of bed elevated 30-45 degrees
Reduce gastric acidity (proton pump inhibitor or H2 blocker)
Endotracheal tube suctioning
Extubation ASAP
```
68
Fungal Pneumonia
Most commonly found in immunocompromised patients
Invasive aspergillosis
(Organ transplant, HIV)
Endemic fungi can be present in immunocompetent people, but often asymptomatic
69
Histoplasmosis
Most common in midwest, along Ohio River Valley
H capsulatum proliferates in soil contaminated with bird and bat droppings
Common cause of calcified granuloma on X-ray
70
Crytococcus
Picked up through contact with soil
Produces multiple, small granulomas on imaging
Co-infects the CNS
71
Blastomycosis
Inhalation of Blastomyces dermatitidis
South eastern and south central US, great lakes
Involves skin
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Coccidiodomycosis
Endemic to Am Southwest; central cali, new mexico, arizona
Spread by pigeons
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Stridor
Sound w/
| Upper airway inflammation and narrowing
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Mycobacterium tuberculosis
Night sweats, hemoptysis (coughing up blood), apical cavitary lesion on chest x-ray
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Lancefield typing
Streptococci based on their carbohydrate surface antigens
| Ex. GBS from GAS
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Fluoroquinolones (mechanism)
Block DNA gyrase and topoisomerase IV
Stops chromosome replication
Not cell wall active like penicillin
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Azithromycin (mechanism)
Blocks protein synthesis by affecting ribosome function
Not cell wall active like Penicillin
