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Pathogens > Pulmonary Pathogens > Flashcards

Pulmonary Pathogens Flashcards

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)

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2
Q

Streptococci

A 
Gram+
Chains
Normal flora of skin and mouth
Facultative anaerobes
Catalase negative
Non-motile, non-spore forming
Exotoxins
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3
Q

Beta-hemolytic Streptococci

A

Group A Streptococci: GAS; S. pyogenes
Strep throat

Group B Streptococci: GBS; S. agalactiae
Neonatal infections, bacteremia

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4
Q

Alpha-hemolytic Streptococci (incomplete lysis of RBCs)

A

“Viridans streptococci”; S mutans; dental carries, endocarditis

Streptococcus pneumoniae: Pneumonia, otitis, meningitis

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5
Q

Gamma-hemolytic Streptococci

A

Enterococcus

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6
Q

Host of S.p., carriage, colonization rate, transmission, higher cases in what population

A
  1. Human to human (humans are only host)
  2. Asymptomatic nasopharyngeal carriage common (5-75% of population; considered commensal)
  3. Colonization rate highest in children
  4. Transmission via respiratory droplets
    Most cases spread from endogenous organisms
  5. Bacteremia and invasive disease higher in AA and Native Am
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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

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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)

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9
Q

Clinical Presentation of Pneumonia (incubation, onset, production, location, risk factors)

A
  1. Aspiration of bacteria and replication in alveolar spaces
  2. 1-30 day incubation period
  3. Abrupt onset of fever and shaking chills
  4. Pleurisy, productive cough, blood tinged sputum
  5. Localized to lower lobes of lungs
  6. Bacteremia occurs in 25-30% of patients
  7. Risk factors include: antecedent resp. viral infection, smoking, age <2 or >65, hematological disorders (asplenia, chronic pulmonary disease, diabetes, renal disease)
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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
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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

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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

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13
Q

S.p. Virulence factors (capsule, PS)

A
  1. Polysaccharide Capsule
    90 serotypes (makes vaccination an issue)
    Essential for pathogenesis
    Immunogenic (responses are directed at capsule)
    Anti-phagocytic
  2. C polysaccharide
    Complex of phosphorylcholine, peptidoglycan, teichoic acid
    Common to all S.p. serotypes
    PResent in urine and serum during infection
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14
Q

S.p. Toxins (3)

A
  1. Pneumolysin (released once cell is lysed)
    Cholesterol-dependent, pore-forming toxin
    Targets bronchial epithelial cells
    Activates classical complement pathway
  2. 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
  3. IgA protease
    Secreted antibody that lines the wall of bronchus, prepares a niche for itself; blunts mucosal adaptive immune response
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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
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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

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17
Q

Treatment of S.p. (susceptibility, resistance, DOC)

A
  1. 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
  2. Isolates also may be resistant to macrolides and to Bactrim
  3. Most are susceptible to fluoroquinolones

DOC: Penicillin (for sensitive isolates); vancomycin or fluoroquinolone + 3rd gen. cephalosporin

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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

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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

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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

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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)

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22
Q

Legionella epidemiology (transmission, location, common sources, outbreaks, risk factors)

A
  1. Transmission via inhalation of aerosols
    No person-person transmission (env. pathogen that gets into lungs by mistake)
  2. Located in fresh water and soil
    Intracellular symbionts of amoebae (lives inside cells, access to nutrients)
  3. Sources: Air conditioning, cooling towers, showers, whirlpools, humidifiers, medical resp. equipment
  4. Outbreaks late summer-fall, large buildings
5. Risk factors:
Increased age
Smoking
Heavy alcohol use
Transplant recipients
Immunocompromised patients (diGeorge)
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23
Q

Facultative Intracellular Legionella (what does it infect, how does it replicate, what does it produce 2)

A
  1. Infects alveolar macrophages
    MOMP adhesin uses C3 complement to stimulate uptake by macrophage
  2. Bacterial replication in phagosomes
    T4SS effectors block acidification/fusion with lysosomes
    “Replicative vacuoles” surrounded by ER
  3. Make hemolysin
    Tissue degradation
    Lysis of RBC
  4. Makes phospholipases
    For vacuolar escape (break out and affect other cells)
    Surfactant degradation
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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
  1. Radiograph pneumonia - yes
  2. Incubation 2-14 days (late summer-fall)
  3. Attack rate <5%
  4. Isolation of organism is possible
  5. Hospitalization is common, case fatality is 5-40%

15-20% mortality (sporadic disease is frequently misdiagnosed)

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25
Q

Pontiac Fever (Features, Radio, Incubation, Attack Rate, Isolation, Outcome)

A

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%
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26
Q

Lab Diagnosis of Legionella (4)

A
  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

  1. Legionella urine antigen:
    Detects only serotype 1 L. pneumophila (majority of infections)
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27
Q

Legionella Treatment and Prevention (activity, antibiotics, source, temperature and treatment of water)

A

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
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28
Q

Mycoplasma (found, size, growth, structure)

A
  1. Extracellular parasite of human mucosal surfaces
2. Small:
Smallest free living organism
Smallest genome
Tissue culture contaminant
(really dependent on host for nutrients)
  1. Slow growth (1-6 hours generation time)
  2. 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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29
Q

Pathogenic Mycoplasma (4)

A 
1. M. pneumoniae
Atypical walking pneumonia
Tracheobronchitis
Mild upper respiratory infections
Joint infections
  1. M. hominis
    Post partum fever, uterine infections, joint infections
  2. M. genitalium, Ureaplasma urealyticum
    Non-gonococcal urethritis
  3. M. fermentans, M. penetrans
    Disseminated infections in AIDS patients
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30
Q

M. pneumoniae cell shape

A

Cytadhesin organelle (arrow)

Penetrates membrane and binds resp. epithelial cells

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31
Q

M. pneumoniae epidemiology (spread, incubation, infection, cases/yr, people at risk)

A
  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
Q

Tracheobronchitis and Pneumonia (pathway)

A
  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
Q

M. pneumoniae Pneumonia (symptoms, CBC, radio, resolution)

A
  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
Q

M. pneumoniae Culture (medium, colonies and inhibition)

A
  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
Q

M. pneumoniae Serology (4)

A
  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
Q

Mycoplasma Treatment (resistance, DOC)

A

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
Q

Paramyxoviruses

A

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
Q

Paramyxoviridae Structure

A

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
Q

Replication of Paramyxoviruses

A
  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
Q

Respiratory Syncytial Virus (RSV) (strains, risk groups)

A

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

Significant cause of respiratory disease in older adults
High risk: Stem cell transplants, severe heart disease, COPD

41
Q

RSV symptoms

A 
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
Q

RSV Lab diagnosis

A

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
Q

RSV Treatment and Prevention (SC, AR, HMA)

A

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
Q 
Human Metapneumovirus (hMPV)
Isolation, distribution, circulation, seropositivity, causes, symptoms, treatment
A

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
Q

Parainfluenza virus (family, serotypes)

A

Paramyxoviridae family
-ssRNA enveloped

Five serotypes (1,2,3,4a,4b)
Reinfection is common because serotypes are different enough
46
Q

Parainfluenza virus pathogenesis (manifestation, causing, driven by, severe disease, mortality)

A

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
Q

Parainfluenza virus Prevention and Therapy (croup, immunocomp, investigational)

A

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
Q

Crackles (Rales) [auscultate, timing, cause, description]

A

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
Q

Gurgles (Rhonchi) [auscultate, timing, cause, description]

A

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
Q

Wheezes [auscultate, timing, cause, description]

A

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
Q

Blood Gas

A

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
Q

Respiratory Alkalosis

A

Blowing off Co2
Becoming more alkalotic (pH increasing)
Tachypnea

53
Q

Respiratory Acidosis

A

Holding onto CO2

Becoming more acidodic

54
Q

CURB65

A 
Confusion
Urea >20mg/dL (renal failure- severe sepsis)
RR >30
BP <90 or <=60
age >65

0-1 outpt
1-2 inpt
>3 ICU

55
Q

HAP

A

Pneumonia occurring 48hours or longer after admission

56
Q

VAP

A

Pneumonia occurring 48hrs or longer after ventilation

57
Q

HCAP

A

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
Q

Aspiration pneumonia or chemical pneumonitis (most common)

A

Aspiration of toxic substance into lungs

Most common substance is gastric contents

59
Q

The most common cause of pneumonia

A

Streptococcus pnemuoniae

60
Q

Common and uncommon causes of pneumonia in pulmonary co-morbid patients (bird owners, HIV/AIDS)

A

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

61
Q

Drug resistance

A
  1. Change ribosomal target so antibiotic can’t bind where it normally does
  2. Prevent entry
  3. Efflux pump
62
Q

Outpt treatment (no co morbid, co morbid)

A

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
Q

Inpt treatment

A

IV or PO levofloxacin
IV cefriaxone and azithromycin

IV in case of vomiting, nausea

64
Q

Healthcare associated pneumonia

A

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
Q

MRSA

A

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
Q

Treatment for MRSA

A

Vancomycin

1+ risk factors: cover MRSA, GN bacilli, MDR Pseudomonas
Piperacillin-tazobactam (b lactam), antipsudomonal fluoroquinolone, linezolid or vancomycin

67
Q

VAP

A

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
Q

Fungal Pneumonia

A

Most commonly found in immunocompromised patients
Invasive aspergillosis
(Organ transplant, HIV)

Endemic fungi can be present in immunocompetent people, but often asymptomatic

69
Q

Histoplasmosis

A

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
Q

Crytococcus

A

Picked up through contact with soil

Produces multiple, small granulomas on imaging

Co-infects the CNS

71
Q

Blastomycosis

A

Inhalation of Blastomyces dermatitidis

South eastern and south central US, great lakes

Involves skin

72
Q

Coccidiodomycosis

A

Endemic to Am Southwest; central cali, new mexico, arizona

Spread by pigeons

73
Q

Stridor

A

Sound w/

Upper airway inflammation and narrowing

74
Q

Mycobacterium tuberculosis

A

Night sweats, hemoptysis (coughing up blood), apical cavitary lesion on chest x-ray

75
Q

Lancefield typing

A

Streptococci based on their carbohydrate surface antigens

Ex. GBS from GAS

76
Q

Fluoroquinolones (mechanism)

A

Block DNA gyrase and topoisomerase IV

Stops chromosome replication

Not cell wall active like penicillin

77
Q

Azithromycin (mechanism)

A

Blocks protein synthesis by affecting ribosome function

Not cell wall active like Penicillin

Pathogens (3 decks)

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