Bacterial Pneumonia 2 Flashcards
Legionella
Gram?
Intracellular?
Free-living form?
natural environment
unnatural environment
Gram(-) Rods
Stains poorly by Gram or H&E – requires silver or IF in tissue sections
Facultative Intracellular Parasites
Free-living form is motile (flagella); intracellular form is non-motile
natural environment: intracellular parasites of freshwater protozoa
unnatural environment: biofilms in commercial water systems, aspirated by humans
Legionella replicates within phagocytic cells
legionella begins living in a biofilm on warm water or in soil and is taken up by phagocytosis
contained in an altered phagosome - bo merged to a lysosome
becomes motile and escapes the phagocome
lyses the cell and spreads to another
humans are an unnatural “dead end” host for legionella
Legionella virulence factors
mip - unknown, required to invade monocytes
dor/Icm locus - type IV secretion system (involved in altering the endosome)
pilE & pilD - pilus formation (attachment)
mak - unknown
mil - unknown
pmi - unknown
pep/pro - zinc metalloprotease (escape)
Three outcomes of legionella infection in humans
- asymptomatic seroconversion
- pontiac fever - fever, incubates hours - 2 days, resolves without complication
- legionnaires disease - pneumonia, suppression of kidney function, incubates 2-10 days, usually resolves with hospitalization and treatment, can be fatal
Risk factors for legionnaires disease
Increasing Age Immunosuppression Smoking Chronic heart or lung disease Chronic swallowing disorder Male For outbreak LD, travel is a common factor: conventions and weddings at hotels
Occurrence and Mortality
Where are hotspots for nosocomial LD outbreaks
~80% of cases are isolated; ~20% present as members of an outbreak
Reportable
Outbreaks are a simultaneously-exposed group: NOT contagious
8000 - 18000 hospitalizations/year in US; 2nd most common pneumonia ICU admit (after pneumococcal)
34% mortality in US in 1985, 11.5% in 1998
Mortality Decreasing because of:
Prompt diagnosis
Early use of appropriate antibiotics
Hospitals are hot spots for LD outbreaks:
Large numbers of at-risk individuals
Old, complex plumbing
Hot water tanks at reduced temperature to prevent scalding
(Fix: thermal mixing valves)
Presentation of LD
Altered mental status Headache High fever/chills Pneumonia/Cough/Chest pain Pancreatitis Acute Renal Failure Diarrhea
Diagnosis of legionella infection
Method #1
Urine antigen test: Commercial ELISA kit
Fast: cell wall component is excreted starting ~3days after symptom onset; test complete in hours Reliably detects the LP1 strain of L pneumophila - causes 90% of LD in US Testing significantly associated w/ reduced mortality
Method 2
Much slower (~1wk)
Technically demanding
Detects many strains and species of Legionella
27% fatality rate among culture-positive, urine-test-negative patients
Tx of Legionella infections
Pontiac Fever often resolves w/o treatment
LD requires an antibiotic that penetrates infected cells:
Levofloxacin (bonus: covers M. pneumoniae and S. pneumoniae)
Azithromycin
Old-school: erythromycin
Post-acute care for LD
Many patients who recover from LD experience
Fatigue
Neurological symptoms
Neuromuscular symptoms
Cough
For up to 17 months. Most recover completely within one year.
Coxiella burnetti: Q fever
Previously grouped with Rickettsia, now a Proteobacteria (closest related pathogen: Legionella)
Zoonosis of asymptomatic infection of ruminants
Transmitted to humans by inhalation of aerosols of infected ruminant urine, feces, birthing matter (no vector!)
Extremely infectious: <10 IUs can cause disease, dried samples remain infectious for months
C. burnetti bacteriology
In humans, multiplies within aveolar monocytes and macrophages, travels in them to liver, spleen, bone marrow.
Virulence factors: acid phosphatase, superoxide dismutases help bacteria survive in FUSED lysosome-endosome
Fairly common in Netherlands, France, Spain, becoming a problem among military & medical personnel in Iraq
C. burnetti pathogenesis/presentation
Fever, chills, sweats Severe headache Dry Cough Pneumonia (~50%) Hepatitis Complications of pregnancy Rare: rash, endocarditis Rarely Fatal Reportable
C. burnetti diagnosis and treatment
Same as Rickettsia: immunohistochemical methods, ELISA, immunofluorescence -> doxcycline or fluoroquinolones
Prevention: Vaccine is available to farm & veterinary personnel and military stationed in Middle East
Mycoplasma pneumoniae - atypical pneumonia
Smallest freeliving organisms (0.3micrometer diameter)
Strictly aerobic
No cell wall (defining characteristic usually peptidoglycan cell wall): little Gram staining, penicillins&cephalosporins ineffective
Only prokaryotic cell membrane that contains cholesterol
Difficult to grow on media, require special nutrients
Colonies have a “fried-egg” shape
Only one serotype, but immunity is incomplete (can recur)
Mycoplasma v myobacter
Mycoplasma pathogenesis
Reside on mucosal surfaces of respiratory and genital tracts
Transmitted by inhalation of respiratory aerosols
Causes tracheobronchitis, bronchiolitis, 5-10% progress to atypical
“walking pneumonia”
Mycoplasma pathogenesis
P1 adhesin binds respiratory epithelial cells
Ciliostasis → dry cough, exacerbates chronic bronchitis, asthma
Local inflammation from bacterial wastes
Tissue destruction by CARDS exotoxin, related to pertussis toxin
Mycoplasma pathogenesis
Intracellular penetration possible
Causes ~20% of community-acquired pneumonias that require admission, more that don’t
Very low mortality <0.1%
Antibodies against mycoplasma (“cold-agglutinins”) cross-react with red blood cell membranes, so patients may become anemic; resolves spontaneously with disease. (this wan’t in the lecture last year)
Mycoplasma diagnosis
Exam: nonspecific upper- or lower-airway, fever, aches&pains, oropharyngeal inflammation, erythematous tympanic membranes, conjunctivitis, rash, lung sounds may include moderate ronchi and rales
Chest radiograph often looks worse than the patient
Lab: self-limited and antibiotic- responsive, labwork not usually required. Culture and molecular testing are available. May be anemic.
Mycoplamsa treatment
Fluoroquinolones cover mycoplasma and all similarly-presenting bacterial infections
Erythromycin, azithromycin, clarithromycin, tetracycline all work slightly better against mycoplasma (intracelluar for tetra)
Longer treatment courses (14-21d) needed because of M’s slow growth, intracellular penetration
Macrolide resistance is emerging in Japan and China
“Other” mycoplasma
Ureaplasma urealyticum and U. parvum can cause male urethritis, possibly also premature birth
M. genitalium can contribute to male urethritis, female cervicitis and PID
Ureaplasma and mycoplasma may both cause bacteremic pneumonia in very premature infants
All can be passed by direct contact, vertically, or nosocomial
