Bacterial Pneumonia Flashcards
Respiratory Immune Defenses
- Mucus
- sIgA
- Lysozyme
- Lactoferrin
- Mucocilliary escalator
- Alveolar MΦ
Respiratory
Immune Compromise
- Preceding URT infection
- Pulmonary disease
- Chemical or mechanical injury
- Generalized host immunocompromise
LRT Infection
Classification
-
Bronchitis ⇒ inflammation of bronchial tree
- Often preceded by URT infection
- Can be part of clinical presentation of influenza, rubella, pertussis, Scarlet fever
-
Pneumonia ⇒ inflammation of lung parenchyma
- Due to many bacteria, viruses, and fungi
- Typical ⇒ acute
- Atypical ⇒ subacute
- Chronic PNA ⇒ takes weeks to months to develop sx
Community Acquired PNA
PNA occuring in usually healthy persons not confined to an institution.
Nosocomial / Hospital Acquired PNA
PNA arising while a patient is hospitalized or living in an institution such as a nursing home.
Lobar PNA
Pulmonary consolidation demarcated by border or segment or lobe
Bronchopneumonia
Patchy consolidation around the larger airways
Interstitial PNA
Fine areas of interstitial infiltration in the lung fields
Aspiration PNA
Follows aspiration of oral or gastric contents leading to damage caused by chemical or mechanical insult.
Bacterial damage may be caused by normal flora such as oral Strep or GI bacteria.
Typical PNA
Differential Dx
-
Strep pneumoniae
- # 1 cause of CAP, nosocomial
- 500k cases/yr in the US
-
Staph aureus
- Secondary pathogen
- Nosocomial
- MRSA vs MSSA
-
Haemophilus influenzae
- Secondary pathogen
-
Klebsiella pneumoniae
- Older, alcoholic, nosocomial
S. pneumoniae
Pathologies
- CAP ⇒ most common cause
-
Meningitis ⇒ leading cause in adults
- May follow PNA or infection @ other site, or w/ no apparent preceding infection
- All ages affected, most common bacterial cause in advanced ages
- Otitis media ⇒ leading cause in children
- Sinusitis
-
Bacteremia ⇒ occurs in 25% of pts w/ infection
- Leads to endocarditis, arthritis, peritonitis, septic shock
- Functional spleen is critical
S. pneumoniae
Epidemiology & Transmission
- Transmission:
- Endogenous usually
- Transmitted via respiratory secretions
- Accompanied by pre-disposing factors
- Epidemiology:
- Infects humans, no reservoir
- 20-40% are carriers in NP
- Incidence greatest < 6 y/o and > 60 y/o
- 1 mil deaths worldwide
Pneumococcal PNA
Risk Factors
- Alcoholism
- DM
- CKD
- Some malignancies
- Bronchial injury d/t smoking or air pollution
- Respiratory dysfunction 2/2 EtOH, narcotics, anesthesia, trauma
S. pneumoniae
Morphology & Characteristics
> 80 serotypes based on capsular polysacc.
In US, 23 serotypes cause > 90% of PNA.
S. pneumoniae
Virulence Factors
-
Polysaccharide capsule ⇒ major factor
- Anti-phagocytic
- Strains w/ large capsules more virulent
- Loss ⇒ avirulent
-
IgA protease
- Aids establishment of infection
-
Pneumolysin
- Toxin w/ pore-forming action
- Injures cilia and endothelial cells ⇒ aids spread
S. pneumoniae
Pathogenesis
- Aspiration of respiratory secretions containing pneumococci into alveoli
- Multiplication of organisms
- Massive inflammatory response, mostly PMNs
- Edema and accumulation of pus
Acute Pneumococcal PNA
Presentation
- Abrupt onset shaking chills, high fever, SOB
-
Significant productive cough w/ pink-rusty sputum
- Sputum: abundant inflammatory cells, single organism predominant, gram ⊕ diplococci
- Pleuritic chest pain on breathing
- Chest sounds
- Dec. breath sounds
- Dullness on percussion
- Rales or crackles
- CXR ⇒ Lobar consolidation
- PMN exudate, clotting of alveolar fluid, ± complete consolidation of one lobe
- Leukocytosis with mostly PMNs
S. pneumoniae
Diagnosis
- Smear ⇒ gram ⊕ cocci
- Culture ⇒ blood agar or blood culture
- Optochin sensitive
- Detection of capsular Ag
- Latex agglutination test
-
Quellung reaction
- Ab to organisms in pure culture or clinical material
- Causes capsule to swell
- Can be used for typing
S. pneumoniae
Immunity
Immunity strain specific & dependent on capsular type.
-
Innate ⇒ important early
- Phagocytosis by PMNs & MΦ
- Alternative complement pathway ⇒ opsonization by C3b
- Both are inefficient d/t polysacc. capsule
-
Acquired ⇒ needed to clear
- Anti-capsular IgG ⇒ opsonization & effective phagocytosis
- Classic complement activation
S. pneumoniae
Treatment
50% are PCN resistant
Fluoroquinolones or Vancomycin for serious disease.
S. pneumoniae
Prevention
-
1st gen vaccine (Pneumovax 23)
- Capsular polysacc. from 23 most common serotypes
- Rec. for high risk pts
-
Conjugate vaccine (Prevnar 13)
- 13 invasive serotypes polysacc. + CRM proteins
- Given to infants as part of routine vaccinations
Klebsiella pneumoniae
Characteristics
Normal flora of oral and GI tract.
Needs to be plated on special media.
Klebsiella pneumoniae
Virulence Factors
- Thick mucoid capsule
- Endotoxin
Klebsiella pneumoniae
Epidemiology & Transmission
- Opportunistic pathogen
-
Endogenous transmission
- Aspiration or via URT
- CAP and HAP
- Affects older pts w/ risk factors
- Alcoholism, smoking, underlying lung disease, nosocomial
- ♂ > ♀
Klebsiella pneumoniae
Pathogenesis & Clinical Presentation
Presents as a typical pneumonia.
Necrotizing w/ production of thick, viscous, bloody sputum ⇒ “currant jelly”
Klebsiella pneumonia
Treatment
-
Inc. resistance to multiple classes of abx
-
CRE ⇒ carbepenem resistant Enterobacteriaceae
- Largely consists of Klebsiella
- Responsible for multiple outbreaks
-
CRE ⇒ carbepenem resistant Enterobacteriaceae
- Choices guided by susceptibility
Pseudomonas aeruginosa
Overview
-
Ubiquitous ⇒ found in soil, water, vegetation
- Prefers moist reservoirs
- Very hardy
- Opportunistic pathogens
Pseudomonas aeruginosa
Morphology and Characteristics
- Gram-⊖ rod
- Aerobic
- Motile
-
Oxidase ⊕
- Aids in differentiation from other enterics
-
Pyocyanin, pyoverdin
- Blue-green pigment on agar media
P. aeruginosa
Transmission & Epidemiology
- Found everywhere
-
Inhabit the hospital environment
- Food, flowers, sinks, respiratory therapy and dialysis equipment, disinfectants
- Hospital personnel ⇒ high rates of carriage
- Transfer to hospitalized pts
P. aeruginosa
Virulence Factors
-
Capsular slime ⇒ mucoid exo-polysacc, alginate
- Under complex regulation
- Forms a biofilm under certain conditions
-
Exotoxin A
- ADP ribosylation of EF-2 ⇒ ⊗ protein synthesis
- Similar to mech. to DT but less potent
- Best correlated w/ virulence
- Ab to exotoxin A are protective
- ADP ribosylation of EF-2 ⇒ ⊗ protein synthesis
-
Endotoxin (LPS)
- Sepsis
- Enterotoxin
- Proteolytic enzymes
- Leukocidin
- Hemolysin
- Pili
P. aeruginosa
Pathologies
Can cause infection of almost any tissue:
- PNA
- Sepsis
- Skin and soft tissue infections
- UTI
- Endocarditis
P. aeruginosa
Risk Factors
- Broad spectrum antimicrobial therapy
- Mechanical ventilation
- CF pts ⇒ PNA
- Burn pts ⇒ sepsis
P. aeruginosa
Pathogenesis
- Usually requires ∆ in host defense
- Causes ~ 15% of all nosocomial infections
- Asymptomatic infection to diffuse b/l bronchopneumonia w/ microabscess formation
- May remain localized @ site of injury or infection
- Bacteremia common ⇒ dissemination & sepsis
- Can cause abscess formation and lung destruction
P. aeruginosa & Cystic Fibrosis
- CF and ventilary assistance ⇒ high risk for PNA
-
Most CF pts have chronic respiratory tract infection by mucoid strains of P. aeruginosa
- Starts ~ 15-18 y/o
- Can cause severe necrotizing bronchopneumonia
P. aeruginosa
Treatment
-
Highly resistant to most abx
- Mediated by multiple mechs
- Inherent and acquired
- Mutation of porin proteins
- Mediated by multiple mechs
- Combo therapy required
- Newer β-lactams & aminoglycosides
- Therapy based on drug susceptibility tests
P. aeruginosa
Prevention
- Eliminating from hospital setting very difficulty
- Preventative measures
- Hand washing
- Air filtration
- Proper disinfection of equipment
- Effective sanitation
- Avoid inappropriate use of broad spectrum abx
- More cases ass. w/ contaminated hot tubs and spas
Primary Atypical Pneumonia
(PAP)
“Walking pneumonia”
- Insidious onset ⇒ malaise, headache, low fever
-
Non or minimally productive cough
- Sputum: PMNs, low/no pathogens vs difficulty staining
- Chest sounds ⇒ scattered crepitations or unremarkable
- CXR ⇒ patchy infiltrate mostly in large airways, little consolidation
- Normal WBC count
Primary Atypical Pneumonia
Etiologies
Syndrome of multiple etiologies.
- Mycoplasma pneumoniae
- Chlamydophila pneumoniae
- Legionella pneumophila
- Chlamydia psittaci
- Coxiella burnetii
- Adenovirus
- Influenza
Mycoplasma pneumoniae
Overview
- Causes 10-15% of all PNA
- # 1 cause of PAP @ 20-25%
- Common cause of tracheobronchitis
- Pharyngitis
M. pneumoniae
Morphology
- Smallest free-living reproductive unit known
- Highly pleomorphic
- No cell wall ⇒ stains very poorly
- Triple layered membrane
- High [sterols]
- Required for growth
- High [sterols]
M. pneumoniae
Transmission and Epidemiology
- Respiratory transmission ⇒ aerosol droplets
- 2-3 week incubation
- Occurs primarily in pre-adolescent and adolescent children
M. pneumoniae
Pathogenesis
- Virulence
- Attaches via P1 adhesin
- Extracellular
- Damages epithelium
- ⊗ Ciliary action
-
Secretes ROI
- Damages bronchial tissue
-
Induces acute inflammation
- Causes most of the damage
M. pneumoniae
Clinical Course
- 2-3 week incubation period
- Sx lasts 1-4 weeks ⇒ “walking PNA”
- Self-limiting diseae
- Convalescence is slow
- Transmission continues during and after clinical recovery
- Sickle cell and other immunocompromised pts ⇒ may have fulminant disease
M. pneumoniae
Diagnosis
- Culture from sputum ⇒ usually impractical
-
Grow on complex media
- Egg based media supplemented w/ lipoprotein, sterols, 5% CO2
- “Fried egg” colonies grow after 3-10 days
-
Cold agglutinins ⇒ IgM to mycoplasma glycolipids that cross-react w/ hRBCs
- Agglutination at low temps
- Single titer > 64 supports Dx
- ⊕ in ½ - ⅔ of symptomatic pts
- False ⊕ ⇒ adenovirus, mononucleosis
- Non-specific assay
-
Complement fixation ⇒ poor sensitivity
- Rise in titer during infection
- High incidence of seropositives in nl population
M. pneumoniae
Treatment
Tetracycline and erythromycin ⇒ effective against all causes of bacterial atypical PNA
Mycoplasmas ⇒ resistant to cell wall inhibitors
Chlamydia
Characteristics
- Small gram ⊖ organisms
- Obligate intracellular pathogens
- Unique life cycle
- Causes respiratory infections, STI, trachoma (leads to blindness)
Chlamydia
Development Cycle
Elementary body (EB) ⇒ transmissible form
Reticulate body (RB) ⇒ replicative form
Site of intracellular binary fission called an inclusion body, can be stained for ID.
Chlamydophila pneumoniae
Characteristics
- Causes PAP similar to M. pneumoniae
- Transmitted person to person
- Causes up to 20% of CAP in young adults
- Implicated in development of asthma and exacerbations
- Ass. w/ inadequate or delayed clearance
Chlamydophila pneumoniae
Clinical Manifestations
- Asymptomatic infections or mild illness
- PAP
- Pharyngitis
- Sinusitis
- Otitis media ⇒ 50% of adults are seropositive
- Asthma development
Chlamydophila pneumoniae
Diagnosis, Treatment, Immunity
Dx: IgM titer of ≥ 15 or IgG titer ≥ 512
Treatment: tetracycline or erythromycin
Immunity: cell-mediated (Th1) mechanism
C. pneumoniae & Atherosclerosis
Hypothesis:
- High titers of Ab in adults w/ CAD
- Organism cultured from atherosclerotic lesions
- Animal models support inflammatory events
- Even mild or asymptomatic infections can cause chronic inflammatory response that may exacerbate atherogenesis
Legionnaire’s Disease
Caused by Legionella pneumophila
First appeared in 1976 @ American Legion Convention in Philadelphia
Causes 10-15% of all pneumonias (CAP & HAP)
Legionella
Characteristics
-
Prefers warm water
- Lakes, streams, coastal ocean
- Small gram ⊖ coccobacilli
- Facultative intracellular pathogen
-
Replicates within amoebas ⇒ forms biofilms
- Infected ameobae can encyst when environment unfavorable
- Free living bacteria enter low metabolic state ⇒ forms biofilms
Legionella
Transmission
-
Infectious aerosols
- No person to person transmission
- Relatively chlorine resistant
- Grow at high temps 46°C
-
Nosocomial pathogen
- Respiratory therapy equipment, ventilators
- Water cooling towers
Legionella
Pathogenesis
- Asymptomatic disease ⇒ common
-
Clinical disease ⇒ usually requires underlying factor
- Advanced age
- Smoking
- Chronic pulmonary disease
- Immunosuppression
- DM
- Clinical disease depends on size of inoclum & host status
- Nosocomial ⇒ outbreaks common in nursing homes
Legionella
Virulence Factors
- Facultative intracellular pathogen, replicates inside Mφ
- ⊗ Phagosome-lysosome fusion
- ⊗ Oxidative and non-oxidative killing
- Hijacks nutrients from cells by coating w/ RER
Legionnaires Disease
Clinical Presentation
- Fever, myalgias, HA, non-productive cough
- Develop into bronchitis, bronchiolitis, and confluent PNA
- Productive cough w/ watery sputum, CP
- Multi-lobe involvement of the lungs
-
GI symptoms ⇒ 50% of cases
- N/V/D, abd pain
- Systemic infection
Legionella
Diagnosis
-
Gram ⊖ coccobacilli
- Poorly staining
- Culture ⇒ requires L-cysteine
- Called buffered charcoal yeast extract
- Slow growth in 3-14 days
- Greyish-white colonies
- EIA of urine ⇒ Group 1 specific LPS antigen
- Serogroup 1 causes 80-90% CAP, 50% HAP
Legionella
Treatment
Macrolides or Quinolones
⇒ Must penetrate infected cells
⇒ Mortality 15-30%
Legionella
Prevention
Monitoring water system
- Hyper-chlorination of water
- Treatment w/ copper or silver ions
- Cycle of superheating (70°C) and flushing
- Maintenance of hot water temp > 50°C
Pontiac Fever
Also caused by Legionella pneumophila
- Mild flu-like URT infection
- Short duration
- Self-limiting
- High attack rate
- Healthy as well as high risk individuals
Zoonotic
Atypical Pneumonia
Animal pathogens that infect humans:
Chlamydia psittaci
Coxiella burnetii
Chlamydia psittaci
- Infects parrots, parakeets, and other birds ⇒ psittacosis
- Can also infect chickens ⇒ ornithosis
- Transmission via respiratory secretions of infected birds
- Living or dead
- Poultry processing at high risk
- Person to person transmission rare
- Dx ⇒ serology
Psittacosis / Ornithosis
- 25-50 cases/yr
-
Mild infections
- Malaise, fever, anorexia, ST, HA, photophobia, non-productive cough
- May include CNS or GI sx
-
Ranges from self-limiting to severe
- Elderly have significant mortality
Coxiella burnetii
-
A Rickesttsial agent
- Includes Rickettsiae, Ehrlichia, Orientia, and Coxiella
- Obligate intracellular gram ⊖ organisms
- Infects ticks, lice, fleas, mites, chigggers, wild and domestic mammals
-
Shed in milk, urine, and feces
- Can get infected from airborne particles formed from urine and feces
- Resistant to heat and dessication
- Causes Q fever
Coxiella burnetii
Transmission
- Contact w/ dust in sheep or cattle sheds
- Ingestion of contaminated milk
- Handling contaminated hides or wool
- Fetal or placental tissue during birthing
- Occupational hazard for tanners, sheep herders and shearers, cattle farmers
- No person-to-person transmission
Q Fever
- Chills, fever, HA, myalgias, malaise
- Pneumonia in 50% of pts
- Hepatitis, endocarditis
- Clinical syndrome lasts 1-4 weeks
- Usually self-limiting w/ gradual resolution
Community Acquired PNA
Etiology Summary
