Mycoplasma/Legionella Flashcards

1
Q

Primary atypical pneumonia

A

Acute infectious pulmonary disease caused by:

Mycoplasma pneumoniae (most common)
Rickettsia 
Chlamydia 
Coxiella burnetii -- Q fever
Adenoviruses 
Parainfluenza virus 
EBV
RSV

Extensive but tenuous pulmonary infiltration and by fever, malaise, myalgia, sore throat, and a cough which at first is nonproductive but becomes productive and paroxysmal

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2
Q

Signs and symptoms of atypical pneumonia

A

insidious onset, fever, malaise, myalgia, headache, sore throat and cough (usually non-productive). Constitutional symptoms often predominate over respiratory symptoms

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3
Q

Expected sputum analysis of atypical pneumonia

A

variable amount; gram stain and routine culture often show only mouth flora

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4
Q

Chest xray of atypical pneumo

A

Pulmonary involvement often greater than expected from mild physical findings. Often see patchy or peribronchial infiltrates, either unilaterally or bilaterally, often with predominantly lower-lobe involvement. Lobar consolidation and pleural effusions are uncommon.

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5
Q

Mycoplasma pneumoniae structure

A

Size – 125-250 nm; smallest free-living organisms.

Pleomorphic (can be almost any shape) – lack cell wall rigidity and can pass through filters.

Colonies – small, slow-growing. Forms small granular colonies without “fried-egg” appearance after incubation for one week or more (different from most colonies).

No cell walls NO peptidoglycan

Resistant to all cell wall-active antibiotics such as penicillins and cephalosporins, and they do not trigger innate immune responses directed against peptidoglycan, teichoic acid, or lipopolysaccharide.

Stain poorly with Gram stain.

Plasma membranes contain sterols, which must be obtained from the growth medium. Mycoplasmas do not synthesize amino acids, metabolize lipids, or synthesize cholesterol.

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6
Q

Growth and nutrition of mycoplasma

A

Can grow on complex but cell-free media; require amino acids, fatty acids, and sterols plus appropriate osmotic conditions

Grow slowly in culture (division time >6 hours for M. pneumoniae, colony formation requires 10-21 days).

Associated in nature with humans and other animals (not free-living).

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7
Q

Priamry disease caused by M. pneumoniae

A
Atypical Pneumonia
Tracheobronchitis
Wheezing in infants
Pharyngitis
Rhinitis
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8
Q

How is M. pneumoniae usually transmitted?

A

respiratory droplets

Attaches to ciliated epithelial cells in the trachea and bronchi of the lower respiratory tract

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9
Q

Specialized structures of M. pneumoniae

A

Elongated shape when it attaches to surfaces.

Specialized tip structure with a dense core that consists of unique cytoskeletal elements. This unique cytoskeletal structure appears to participate both in binary division and in gliding motility of M. pneumoniae on surfaces.

Attachment factor = protein P1 and a complex of other interacting proteins. Protein P1 exhibits antigenic variation among different isolates of M. pneumoniae. The P1 attachment protein is concentrated on the cell membrane overlying this specialized tip structure, although smaller amounts are present in other parts of the cell membrane.

Cell membrane receptor(s) for attachment of M. pneumoniae: sialoglycoconjugates and sulfated glycolipids have been implicated

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10
Q

What are the mechanisms of host injury of mycoplasma?

A

Immobilization of cilia of respiratory epithelial cells (ciliostasis) facilitates microbial contamination of lower respiratory tract and interferes with clearance of microbes and secretions.

Produces H202 and other reactive oxygen species that contribute to tissue damage.

M. pneumoniae infection elicits production of many cytokines (including TNF-α, IFN-γ, IL-1β, IL-2, IL-4, IL-5, IL-6, IL-8, IL-10 and IL-18) that contribute both to clearance of the bacteria and to the disease process.

A novel ADP-ribosylating toxin (CARDS-TX) was reported in 2006 and shown to cause damage to cells in culture that resembles cytopathic effects seen in the respiratory epithelium of infected animals.

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11
Q

Treatment of mycoplasma

A

oral doxycycline (not in kids)
or
macrolides (e.g., erythromycin, clarithromycin, or azithromycin)
or
fluoroquinolones (levofloxacin, moxifloxacin, or gemifloxacin)

Several regimens of intravenous antibiotics are used to treat hospitialized patients with community-acquired pneumonia.

Resistance to macrolides is emerging in M. pneumoniae

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12
Q

Structure and staining of legionella

A

Motile, pleomorphic gram-negative rod (stains poorly with gram stain); non-spore forming.

The bacteria are easily stained by fluorescent antibody methods or silver stains, but staining is less sensitive than culture for detecting them

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13
Q

Growth requirements of legionella

A

Growth occurs over a wide temperature range, requires cysteine and iron, and is fastidious.

Optimal growth in the laboratory occurs on buffered charcoal-yeast extract (BCYE) medium at 35C, and growth is slow (2-6 days to form colonies).

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14
Q

Other characteristics of Legionella (oxidase positive or negative? Catalase positive or negative? Antibiotic susceptibility? What does it produce?)

A

Oxidase and catalase positive.

Resistant to penicillin because it produces a β-lactamase.

Also produces a hemolysin and a cytotoxin.

Does weird coiling phagocytosis that is distinct but unclear how important it is

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15
Q

Pontiac Fever

A

Caused by Legionella infection

Acute, self-limited febrile illness (no pneumonia)

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16
Q

Legionnaires’ disease

A

Symptoms can be extremely variable from mild to severe.

The incubation period is long.

Often the disease presents as pneumonia with fever, malaise, chills, cough (90% of cases), chest pain, headache, diarrhea (30-50% of cases). Extra-pulmonary symptoms are more common that for many other bacterial pneumonias

17
Q

Route of entry of Legionella

A

inhalation, aspiration

Spread by inhalation or ingestion of water from aquatic ecosystems or potable water distribution systems contaminated with Legionella.

The role of contaminated non-potable water from cooling systems appears to be less important than indicated by early studies.

Legionnaire’s disease is not transmitted from person-to-person.

18
Q

How does Legionella avoid host defense mechanisms?

A

By living within macrophages (a facultative intracellular
pathogen).

Inhibits endosome-lysosome fusion. Endosomes become associated with endoplasmic reticulum to form “ribosome-studded” phagosomes.

19
Q

Patterns of disease with legionella

A

can occur in sporadic, endemic, and epidemic forms; higher incidence in late summer, early fall; low attack rate (less than 5%)

20
Q

Diagnosis of Legionella infection

A
Demonstration of bacteria in tissue or secretions:
Cultures
Sputum
Silver stain
immunofluorescence 

Urine antigen test

Serology

Molecular diagnostic tests

21
Q

Treatment of Legionella infection

A

Newer macrolides (such as azithromycin or clarithromycin)

quinolones (such as levofloxacin, ciprofloxacin or moxifloxacin)

a ketolide (telithromycin)

tetracyclines (doxycycline, minocycline, tetracycline, tigecycline)

and others (trimethoprim-sulfzmethoxazole, rifampin).

22
Q

CARDS-TX

A

“Community Acquired Respiratory Distress Syndrome Toxin (CARDS TX)”

Significant virulence factor for M. pneumoniae

Amino acid sequence homology with the enzymatically active S1 subunit of pertussis toxin

Shares three active-site motifs with several bacterial ADP ribosylating toxins

Purified toxin has ADP ribosylating activity, induces cytopathic effects and vacuolization in mammalian cells, and causes slowing and disorganized ciliary movement plus histopathological changes in baboon tracheal organ cultures

Patients with acute M. pneumoniae infections develop antibodies against CARDS TX

23
Q

Diagnosis of M. pneumo

A

Difficult b/c takes a long time to culture and complement fixation and cold aglutinin tests are used more for epidemiology than for practical diagnosing purposes

Can use a combo of PCR and serology for diagnosis

24
Q

Clinical clues suggestive of Legionnaire’s disease

A

Diarrhea

High fever (greater than 40 C and 104 F)

Numerous neutrophils but no organisms on Gram stain of sputum

Hyponatremia

Failure to respond to beta-lactam drugs and
aminoglycosides

Water supply contaminated with Legionella

Onset of symptoms within 10 days of hospital discharge