Atypical pneumonia

Question 1

What is the definition of atypical pneumonia?

Answer 1

Typically used to refer to a pneumonia cause by an atypical pathogen

• Mycoplasma pneumoniae
• Legionella pneumophila
• Chlamydophila pneumoniae
• Viruses
• recalcitrant to culture by traditional microbiological techniques

Question 2

What is the atypical pathogen Legionella pneumophila?

Answer 2

• Causes: legionnaires disease
• gram negative rod
• intracellular
• 15 serogroups
• form commensal relationships with amoeba

Question 3

What is the source of Legionella pneumophila?

Answer 3

• ubiquitous in fresh water
• other habitats (human made): air con, showers, fountains
• in nature, replicate within amoeba (protection from environmental stress)
• biofilm formation reported

Question 4

How is Legionella pneumophila transmitted ?

Answer 4

• Human to human spread not reported until 2016

- Typically inhalation of contaminated aerosols

Question 5

Describe Legionella pneumophila replication in alveolar macrophages

Answer 5

• Inhalation of contaminated aerosol leading to established infection.
• Intracellular replication of LP in alveolar macrophage
• Legionella replication can occur within macrophage
• LAMP – marker of digestive vacuole developing
• With legionella, vacuole starts to take on various membrane bound organelles within the macrophage (ER, mitochondria, ribosomes) – now an environment the legionella can use for replication rather than being broken down and digestive. Pathogen is able to escape the macrophage and infect another one

Question 6

What is the clinical presentation of Legionella pneumophila?

Answer 6

Generally most severe of atypical pneumonias
Incubation period 2-10 days

Initial phase (2d) 
Flu like illness

Then…
Fever, myalgias, confusion
Non productive cough
Potential acute renal failure

Case mortality rate – variable (up to 24%)

Question 7

What is the atypical pathogen Mycoplasma pneumoniae?

Answer 7

Very Small (1-2μm x 0.1-0.2 μm)

No cell wall - has triple membrane structure to protect it

Limited biosynthetic capability

Rarely found free living in nature

Require rich, complex growth media for in vitro culture - difficult to grow

Genome is so small – useless in terms of making its own ‘stuff’: needs to scavenge a lot from the host in order to get all the necessary nutrients

Question 8

What is the clinical presentation of Mycoplasma pneumoniae?

Answer 8

Insidious onset – sore throat, malaise…

day 3: Chest symptoms
Dry cough - infective
Often paroxysmal cough, similar to whooping cough

Radiographic changes
Bilateral pneumonia (20% cases)

Question 9

What may cause paroxysmal cough?

Answer 9

• toxin production
• Previously thought to not produce toxin due to genome size, but…
• Community acquired respiratory distress syndrome toxin (CARDS)
  
  • Surface binding via phosphatidylcholine and sphingomyelin
  • Similarities with Pertussis Toxin (2nd year Public)
  • Cessation of cilia movement (stops)
  • Cellular vacuolation

Question 10

What is the generalised treatment for atypical pneumonia (non-pregnant adult)?

Answer 10

1st line macrolide. One of the following options
Clarithromycin (14-21d, b.d.s)
Azithromycin (4d, once daily, orally OR 5d, once daily, IV)
Erythromycin (14-21d, q.d.s)

Macrolides cover AP and numerous CAP causes. IV formulations are also available should the patient be unable to take drugs orally.

OR… 1st line Tetracycline
Doxycycline (14d, b.d.s)
2nd line Fluoroquinolone
Levofloxacin (5d, once daily)

Doxycycline covers most AP and CAP causes but is also first-line treatment for zoonotic atypical pathogens, including Chlamydophila and Coxiella

Question 11

What is the generalised treatment for atypical pneumonia (pregnant or child)?

Answer 11

1st line macrolide. One of the following options
Azithromycin (children > 3 months or adults)
Erythromycin (14-21d, q.d.s)
Clarithromycin (children > 3 months or adults; 14-21d)

Macrolides cover AP and numerous CAP causes. IV formulations are also available should the patient be unable to take drugs orally.

2nd line doxycycline or Fluoroquinolone – Due to resistance?
Consult specialist for dose
Doxycycline not recommended in children <12y or pregnant women. – can cause permanent discolouration of teeth in under 12s and foetal skeletal development in pregnant women

*If you are dealing with Macrolide resistant organism – you will need to look for alternatives
There are no beta-lactams as they target the bacterium cell wall, and as mycoplasma have no cell wall, they would be useless