repiratory Flashcards
3 ways of moving bacteria out of the resp system
- cilia
- engulfing in epithelial cells and then desquamating
- macrophages
smokers are often colonized with which bacterias that cause pneumonia?
- s. pneumoniae
2. H. influenzae
patients with CF are often predisposed to what type of bacterial infection?
P aeruginosa– which form biofilms
pneumococcus physical manifestations
abrupt onset, fever, chills, cough, severe pleuritic chest pain by the infected lobe, tachypnea and SOB, productive cough, thick, rusty colored sputum
sputum from someone with pneumococcus is rusty colored and has
Gram Pos lancet shaped doplococci
PMNs
complications from pneumococcus
empyema and bacteremia with metastatic infection, particularly of the joints and occasionaly the meninges
the most common cause of community acquired pneumonia in the states
pneumococcus (S pneumoniae)
risk factors for S. pneumoniae
smoking, ETOH, infection with influenzae, COPD, asthma, splenectomy, immunocompromised (HIV, multiple myeloma, lupus, transplantation), homelessness, pregnancy, crack/cocaine
how can you detect S. pneumoniae
sputum culture– although it doesn’t last long
urinary Ag test detects bacterial wall components
spread of S. pneumoniae from person to person
aerosol inhalation —> colonization in the nasopharynx
how does S. pneumonia invade?
colonizes nasopharynx —>binds receptor of platelet activating factor (PAF) —> and to the disaccharide N-acetylgalactosamine B1-4 galactose —> promotes invasion of cells
also, pneumolysin is a toxin that binds cholesterol/creates pores in cell membranes. It promotes intra-alveolar replication, penetration of org into IT, and dissemination of org by killing host imm cells.
what is pneumolysin
toxin associated with S. pneumoniae that binds cholesterol/creates pores in cell membranes. It promotes intra-alveolar replication, penetration of org into IT, and dissemination of org by killing host imm cells.
cholesterol binding, pore forming toxin in s. pneumoniae
pneumolysin
cholesterol binding, pore forming toxin in Group A strep (pyogenes)
streptolysin O
cholesterol binding, pore forming toxin in clostridium perfinigens
perfringolysin O
cholesterol binding, pore forming toxin in listeria monocytogenes
listeriolysin O
Txt of pneumococcal (S. pneumoniae)
standard thereapy for community acquired pneumonia (macrolides (like azithromycin) or amoxycillin in combo with a second agent) provides coverage for Penicillin susceptible and resistant strands
how long should S. pneumoniae be treated for?
non-complicated: 5-7 days, complicated with bacteremia: 10-14 days
how is S. pneumoniae prevented?
vaccination of children < 5- protein conjugate vaccine to polysaccharide Ag from 13 serotypes
vaccination of adults: polysaccharide vacine with purified capsular polysac Ag from 23 serotypes
*over 90 serotypes
pseudomonas aeruginosa disease
nothing to differentiate it from other pyogenic pneumonias: cough productive of purulent sputum, dyspnea, fever, chills, confusion and severe systemic toxicity
what do chest x-rays for pseudomonas aeruginosa pneumonia look like?
multi focal infiltrates
what is the most common gram negative pathogen implicated in both hospital acquired and ventilator-associated pneumonia?
pseudomonas aeruginosa
people with CF and other immunocompromised pos are particularly susceptible to what pneumonia?
pseudomonas aeruginosa
pseudomonas aeruginosa
gram stain/shape:
motile:
oxidase status?
gram negative bacilli, motile by flagella, oxidase positive
detection of pseudomonas aeruginosa
culture from sputum
- produces a sweet grape like odor and elaborates a green pigment
- oxidase positive
- gram negative bacilli
“non enteric gram negative rod” is highly likey to be pseudomonas aeruginosa
how does pseudomonas aeruginosa get into the host?
likely via aspiration of organism from contamination of ventilator
which bacterial pneumonia has the propensity to form biofilms?
pseudomonas aeruginosa
why does the production of a biofilm make pseudomonas aeruginosa more difficult to treat?
adherent aggregates of bacterial cells that form on surfaces. bacteria of biofilm secrete ECM and as a result, bacteria within the biofilm become resistant to many types of Abx
how is pseudomonas aeruginosa further protected by prolonged infection
pseudomonas aeruginosa converts to a mucoid phenotype that is due to the production of alginate, an exopolysaccharide. Alginate protexts the organism from phagocytosis, making eradication very difficult!
- this occurs even more in pt with CF
txt of pseudomonas aeruginosa
- initial txt with extended spectrum anti-pseudomonal penicillin or a cephalosporin with activity agst pseudomonas. If susceptible, a flouroquinolone (like ciproflaxocin) will work
pseudomonas aeruginosa is often resistant to first and second gen penicillins/cephalosporins
why is pseudomonas aeruginosa so hard to treat (4)
poor penetration of abx into purulent airway secretions, abx resistance of the isolate, CF-related defects in mucosal defenses, and biofilms
Corneybacterium diptheriae disease
acute resp illness characterized by: thick membrane forms on tonsils/adjacent structures (a dense necrotic coagulum of fibrin, leukocytes, and cell debris secondary to cytotoxic orgs)
low grade fever, malaise, sore throat
rare but significant complication of diptheria?
suffocation due to aspiration of the membrane
txt time in uncomplicated cases of diptheria?
5-10 days, infection resolves/membrane is coughed up
how is diptheria spread?
droplet and contact with infected secretions
Corneybacterium diptheriae
gram stain/shape:
what distinguishes it from other corneybacterium?
gram stain/shape: gram positive rod
distinguishes it from other corneybacterium: exotoxin
detection of corneybacterium diptheriae
primarily clinical and some culture (gram positive rods)
diptheria toxin
a protein exotoxin that causes all aspects of diptheria disease
is corneybacterium diptheriae IC or EC?
EC, but it causes damage with the exotoxin: diptheria toxin
mechanism of action of diptheria toxin
AB toxin.
B subunit binds cell surface receptor normally for GF —> endosome —> low pH causes AB toxin to fold/expose hydrophobic portions —>interacts with the lipid membrane —> A portion gets into cytosol and binds ADP-ribosylates EF-2 —-> stops protein synthesis /leads to cell death
whic two AB toxins target EF-2/stop protein synthesis in a cell
diptheria toxin and pseudomonas exotoxin A
txt of diptheria
an antitoxin – but it only neutralizes EC toxins, so you have to administer it early in the course of disease
preventing diptheria?
immuniation with formalin-inactivated toxin is protective. Used to be DPT (diptheria, pertussis-tetanus), but now DTaP (diptheria-tetanus-acellular pertussis)
Mycobacterium tuberculosis manifestations
pulmonary disease:
primary infection: limited to the lungs
pneumonia: slowly progressive and can last for months, dry cough, fever, night sweats, and striking weight loss
pneumonitis (inflammation in the lung that may or may not have an infectious etiology)
pt with normal immune systems generally dvp what as a result of TB? what about immunocompromised pt?
normal: pneumonia
immunocompromised: extrapulmoary tb (inc basilar meningitis)
M. tuberculosis
reservoir:
stain:
M. tuberculosis
reservoir: human pathogen with no known envt/zoonotic reservoir
stain: unusual lipid content of cell wall, does not stain with Gram stain, but is acid fast
how is M. TB detected?
acid fast staining and culture of infected specimens (sputum or lung tissue from bronchoscopy)
how does PPD work
infx w/ m. TB produces delayed-type hypersensitivity rxn to antigenic components (tuberculins) that = contained in extract of culture filtrate of the organism. DTH (delayed type hypersens) indicates the presence of an immune memory to the Ag that is mediated by specific T cells
false positive PPD can be caused by
BCG vaccine (given for Tb in other parts of the world) or infection with non-tb mycobacterium
pathogenesis of primary TB infection
spread by droplet —> settle in alveoli—> phag. by alveolar macrophage —> can become symptomatic with pneumonia. Inside the macrophage, TB lives in vacuoles and blocks linkage with phagosomes
pathogenesis of systematic spread of TB
from the alveoli —> bacteria (tubercle bacili) gain access to blood steram within macrophages —> seeding of other organs especially liver and spleen. Tuberculosis are designed to live within macrophages, not be destroyed by them (Inside the macrophage, TB lives in vacuoles and blocks linkage with phagosomes)
how does tb modify the phagosome to avoid being killed (3)
1) prevent acidification of phagosome by exclusion of vacuolar proton ATPase
2. preven phagosomal-lysosomal fusion by altering prot content of phag. membrane (retention of Rab5)
3. maintain fusion competence so that the phagosome can fuse with other endosomes that provide protein food for tb)
TB is able to degrade what ROS that is usually used by macrophages to kill bacteria
NO
RD-1
a genetic locus that is critical to the virulence of M tuberculosis– it encodes secretory pathway that is responsible for the secretion of bacterial factors that interact with the host
granulomas
a conglomeration of tubercle bacilli and dead and live macrophages – a hallmark of tb infection
persistence
the ability of a pathogen to remain in the human host over a prolonged period of time, although not causing symptoms during that time
latent tb
the period in which the infected person does not have clinically apparent tb, but harbors orgs that can reactivate
how does TB avoid the humoral immune response?
by living in IC vacuoles
how does tb avoid the cellular immune response
it inhibits the release of cytokines that are important to mounting a cell-mediated response, in particular IL-12
what is distinctive about mycobacterial cell wall?
mycolic acids (long chained fatty acids), distinctive lipids and glycolipids are present in mycobacterium and not other bact. these cell wall constituents are imp. for modulation of immune response, and therefore increased persistence of the org in the host
why does tb txt have to be so long
tb is very slow growing and when they’re only present in granulomas they are in an altered metabolic state that has shifted from aerobic to anaerobic. Since all current tb drugs target cell processes involved in cell growth and replication, the altered state of tubercle bacilli leads to relatively poor killing of the orgs
Legionnaire’s disease (legionella)
community-acquired pneumonia that presents with fevers, a minimally productive cough, dyspnea, elevation of LFTs
natural reservoir of Legionnella/source of infection
a free-living amoebae– infection post exposure to contaminated source : AC ventilation or water distribution system
Legionnella
gram/shape:
gram negative rod
85% of Legionnella infections are caused by
L. pneumophilia
Detection of L. pneumophilia (legionnella pneumophilia)
a urinary Ag assay for L. pneumophilia serogroup 1 or ID of organism in sputum/specimens from bronchoscopy direct staining with Ab
pathogenesis of legionnella pneumophilia
IC pathogens that have evolved for survival within vacuoles of macrophages. A special secretion system (different from T3) delivers bacterial proteins into macrophage cytosol that block phagosome maturation/phag-lysosome fusion.
Additionally, ribosomes are drawn to the phagosome, so that prots can be used by bact. Bacteria can then multiply in phagosome, eventually leading to cell lysis
L. pneumophilia and TB both survive where?
in vacuoles within macrophages
txt of legionella ifxn
2 wk course of Abx
