Lec10 Atypical Pneumonia Flashcards
What are signs of typical pneumonia?
- abrupt onsent
- productive cough
- copious sputum
- evidence of consolidation on exam
- high WBC count
- distinct infilitrate on chest xray
What are signs of atypical pneumonia?
- insidious onset
- extrapulmonary symptoms [headahces, muscle aches]
- usually no consolidation on exam
- fever rarely > 101
- normal WBC
- less distinct infiltrate on chest xray
What are 3 most frequent causes of atypical pneumonia?
- mycoplasma pneumoniae
- chlamydophila pneumoniae
- legionella species
What are some other common etiologies of atypical pneumonia [besides the 3 main bacteria]?
- coxiella burnetii [q fever]
- respiratory viruses
What is epidemiology of mycoplasma pneumoniae?
- in mini outbreaks in households
- incubation 2-3 wks
- gives young children URI, others primary penumonia
How is mycoplasma pneumoniae transmitted?
- by respiratory droplet
- need close contact
- much longer incubation than viral infections
What is structure of mycoplasma pneumoniae? shape? gram stain? etc?
- lacks cell wall
- contains RNA and DNA
- short rod-shaped
- not visible on gram stain
- can grow on cell free medium
- long doubling time so takes many days to grow in culture
What are extrapulmonary manifestations of mycoplasma pneumoniae?
- hepatitis
- hemolysis
- rash [erythema multiforme]
- rarely: myocarditis, encephalitis
What are the virulence factors of mycoplasma pneumoniae? who is particularly at risk?
- virulence factors located intracellularly
- patient age relates to likelhood of progression —> adolescent, young adult, elderly more at risk
- high disease rate [and more severe infection] in sickle-cell disease
What is the host immune response to mycoplasma pneumoniae?
- polyclonal T cell and B cell activation
- variety of antibodies produced including antibodies [cold agglutins]
What are cold agglutinins?
- autoantibodies produced in immune response
- IgM antibodies directed at the I antigen on RBC surface
What are the clinical manifestations of mycoplasma pneumoniae?
respiratory: upper to lower
skin: erythema multiforme
cardiac: arrythmia, CHF
neuro: meningitis
other: renal, liver, musculoskeletal
How do you diagnose mycoplasma pneumoniae infection?
- usually on clinical basis
- can use complement-fixing antibodies to confirm diagnosis retrospectively
- culture techniques and cold-agglutinin test not useful [not specific/sensitive/too cumbersome]
How do you treat mycoplasma pneumoniae?
- no cell wall so can’t use penicillins/cephalosporins
- use macrolides [erythromycins] or tetracyclines
- most cases undetected or untreated
- no vaccine
What is epi of chlamydophila pneumoniae
- associated with epidemics
- older the host –> more likely to cause lower rather than upper respiratory infection
How is chlamydophila pneumoniae transmitted?
by respiratory droplets
What is structure/shape of chlamydophila pneumoniae?
- intracellular bacteria
- have cell walls
- not seen on gram stain
What is the elementary body vs reticulate body of chlamydophila pneumoniae?
elementary body = metabolically inacive infectious form, can survive outside the cell
one inside the cell it becomes the reticulate body = starts replicating
What are the virulence factors for c. pneumoniae?
- no specific virulence factors identified
- located intracellularly
What is the pathogenesis of c. pneumoniae?
- enters via respiratory tract
- can persist in respiratory epithelial cells for prolonged period before and after acute infection
What are the clinical signs of chlamydophila pneumoniae?
- commonly asymptomatic
- patchy pneumonia without fever
- occassionaly upper respiratory symptoms [rhinitis, sore throat]
- persistent cough
- otisis, and rarely pericarditis or pleuritis
- may be implicated in atherosclerosis
How is c. pneumoniae diagnosed?
- usually presumed from clinial signs
- can use IgM antibody to detect recent infection in serum
- can use IgG antibody to detect remote or recent infection
How is c. pneumoniae treated?
- teatracyclines, macrolides [clarithromycin, azithromycin], newer fluroquinolones
How is legionella pneumophila transmitted?
- lived in aqueous habitats
- transmit to humans though inhalation following aerosolization
- no person-person transmission
- incubation = 2-10 days
What is structure of l. pneumophila? gram?
- small bacilli
- gram negative [but weakly]
- aerobe
- fastidious growth –> need special media to isolate
- 16 serotypes but group 1 causes most human infections
What are the virulence factors of l. pneumophila?
- variety of toxins and protease
- on surface:
- – pili promote adherence to target cell
- – flagellae promote entry into cell
- – macrophage infectivity promoter protein
What is the pathogenesis of L. pneumophila infection?
- organism reaches lung and phagocytoses by alveolar macrophages
- grows in cell and eventually kill and infect other macrophages
- neutrophils infiltrate alveoli and fluid leaks from capillaries into interstitium of lung
- sever inflammatory cytokine response to dying macrophages
What type of host immune response?
both cellular and humoral
What are the clinical signs of L. pneumophila?
- prodromal illness [fever, malaise]
- mild to life threatening pneumonia
- hepatitis, rhabdomyolosis, renal failure, abscesses, altered mental status etc
- may start with altered mental status and diarrhea
How is L. pneumophila diagnoses?
- culture respiratory secretions on selective media [buffered charcoal yeast extract, use silver stain]
- detect antigen of serogroup 1 in urine
- direct fluorescent antibody staining of respiratory secretions
- insensitive to serum antibody test
How is L. pneumophila treated?
- macrolides [azithromycin], tetracyclines, fluoroquinolones [levofloxacin]
- high mortality in immunocompromised and elderly
What are the two macrolide antibiotics?
- clarithromycin
- azithromycin
What is mech of action of macrolides [clarithromycin, azithromycin]? bacteriostatic or bactericidal?
- bind 50s ribosomal subunit
- inhibit RNA-dependent protein synthesis
- bacteriostatic
What are the PK properties of clarithromycin? [oral or intravenous, half life, elimination]
- given orally
- metabolized by liver
- 30% excreted unchanged in urine
- 3-4 hr elimination half life
What are the PK properties of azithromycin? [oral or intravenous, half life, elimination]
- given orally or intravenously
- if orally needs to be on empty stomach [food interferes with absorption]
- wide distribution in tissues, 2-4 day elimination half life
- eliminated unmetabolized through bile
What toxicities associated with macrolides?
frequent: diarrhea, nausea, abdominal pain
less frequent: dizziness, temporary hearing loss, ventricular arrhythmia
What are the 3 fluroquinolone antibiotics?
- moxifloxacin
- levofloxacin
- ciprofloxacin
Mech of action of fluoroquinolones?
- inhibit DNA synthesis by:
- inhibiting DNA gyrase
- inhibiting topoisomerase IV
What are the PK properites of fluoroquinolones? [oral or intravenous, half life]
- all 3 given orally or intravenously
- absorbed well from GI
- reach high conc in all tissues with long half lives
How is levofloxacin eliminated? ciprofloxacin? moxifloxacin?
levo and cipro by kidneys
moxi primarily via liver in the bile
What toxicities associated with fluoroquinolones?
most frequent: anorexia, nausea, vomiting, abdominal pain, diarrhea
less frequent: headache, dizziness, cartilage erosions, tendonitis/tendon rupture, mania, seizures, hallucination
- avoided in peds because of potential effect on growing cartilage
If you have GI problems, confusion and 2-3 days later get pneumonia what should you think?
legionella!
