ICU Fellowship Snippet – Legionella Pneumonia

A 59-year-old male presents to an outer metropolitan hospital, supported by a non-tertiary ICU, with severe respiratory failure. He gives a history of a week of cough, myalgia, fevers and increasing shortness of breath. What is your differential diagnosis?

Written by Dr Madhuri Anupindi

There are many potential causes for this presentation, most likely infectious aetiologies, whether bacterial, viral, fungal or parasitic, although his presentation may also be secondary to non-infectious causes.

Infectious:

• Bacterial
  • Community-acquired pneumonia, e.g. streptococcus pneumoniae, mycoplasma, h. influenzae, legionella
  • Infective endocarditis
  • Sepsis from another source with multi-organ involvement e.g. septic joint, meningitis, soft tissue infection
• Viral
  • Influenza or viral pneumonia such as COVID
  • CMV
  • EBV
• Fungal
  • Cryptococcal meningitis
  • Candidemia
  • Aspergillosis
  • PJP
• Parasitic
  • Malaria

Non-infectious

• Cardiovascular
  • Cardiac failure
  • PE
  • Diffuse alveolar haemorrhage
  • Mitral valve prolapse
• Inflammatory/infiltrative
  • Sarcoidosis
  • Vasculitis
  • Eosinophilic pneumonitis
  • Aspiration pneumonitis
  • Pancreatitis with SIRS response
• Autoimmune
  • SLE
• Neoplastic
  • Lymphoma/haem malignancy
  • Lymphangitis carcinomatosis
• Drug toxicity or chemical pneumonitis
• COPD or asthma exacerbation
• Neuromuscular
  • Neurogenic pulmonary oedema
  • Neuromuscular disease

What other aspects of the history would be important to help confirm a specific infective aetiology for his presentation?

Presenting complaint:

• Any other localising symptoms (apart from respiratory) e.g. soft tissue, neurological à may be sepsis with respiratory involvement

Co-morbidities:

• Immunosuppression e.g. malignancy, steroid use, renal failure: infections in the immunocompromised host
• Lung disease e.g. asthma, COPD: increased risk of pneumonia
• Previous splenectomy: risk of encapsulated organisms
• Presence of lines e.g. ports or devices: risk of infection
• Smoking: increases risk of pneumonia e.g. legionella, pneumococcal, staph
• Heavy alcohol use: increases risk of pneumonia e.g. H.influenzae, strep pneumoniae, legionella
• Intravenous drug use: risk of blood-borne infections, endocarditis, staph aureus

Exposures:

• Unwell contacts: may help identify the organism/route of transmission
• Travel and immunisation history: endemic organisms and travel-related infectious diseases
• Unprotected sex: risk of HIV – seroconversion illness or immunocompromise
• Recent antibiotic use, hospitalisation, residential care: risk of multi-resistant organisms
• Exposure to birds: risk of Chlamydia Psittacosis
• Recent gardening: Legionella Longbeachae
• Recent exposure to tropics in wet season/flooding: melioidosis, leptospirosis
• Work or encounters with farm animals e.g. working in abattoir, vets, shearers – risk of chlamydia, Q fever

Further history reveals that he is otherwise healthy, has a 20 pack year smoking history but no history of other drug or alcohol use. He has been at a conference in London (remained in the city) and returned ten days ago. What investigations would you perform to aid in your diagnosis of the infection causing his respiratory failure?

Blood tests:

• FBC: leucocytosis or leukopenia and neutrophilia could indicate bacterial cause, lymphocytosis could indicate viral
• Atypical serology (Mycoplasma, Legionella, Chlamydia)
• Blood culture: bacteria
• UEC: hyponatremia more common in Legionella
• LFTs: deranged LFTs more common in Legionella, Chlamydia psittacosis or Q fever infection

Imaging

• CXR: lobar consolidation likely bacterial pneumonia such as Strep pneumoniae, multi-lobar or cavitation may suggest Staph aureus
• CT chest

Other:

• Sputum MCS if productive cough present
• Urinary antigens: Strep. pneumoniae and Legionella pneumophila
• Respiratory viral nasopharyngeal swab: influenza A and B, COVID, RSV, Parechovirus, Human Parainfluenza , Enterovirus, Adenovirus, Metapneumovirus, Bordetella – also tests for Mycoplasma Pneumoniae

The Legionella urinary antigen comes back positive. Outline the transmission and other methods available to diagnose Legionella Pneumophila?

Legionella are aerobic, gram-negative intracellular bacilli. There are  over 50 species however the two most common that are pathogenic in humans is Legionella Pneumophilia (mostly serogroup 1) and Legionella Longbeachae. Legionella pneumophila thrive in warm water and thus grow readily in closed manmade water systems such as inside plumbing fixtures. It is transmitted via inhalation of aerosols, mostly from contaminated water sources such as showers, pools, humidifiers, aquariums and air conditioning systems. It can also rarely occur by aspiration of contaminated water or ice. It cannot be spread person to person.

The urinary antigen only detects Legionella Pneumophila serogroup 1, not Legionella Longbeachae species but it is a very rapid test. Other methods available to diagnose L. Pneumophila are:

• PCR:
  • Can be used on sputum, urine and serum and is fast but not available in some labs
  • Sensitivity 95%, specificity > 99%
  • Can detect species other than Pneumophila
• Serology
  • For most accurate interpretation requires acute and convalescent serology 4 weeks apart
    • Criteria for positive include a 4x increase in titre to 1:128 or higher
    • A single high titre IgG or positive IgM is suggestive of infection but not confirmatory
  • Sensitivity of paired serology is 80 – 90% and specificity is > 99%
  • More useful for epidemiologic information
• Culture
  • Considered the gold standard but requires specialised media and generally a bronchoscopic sample. Expectorated sputum can be used but are less ideal due to contamination with oral flora and relatively low Legionella content.
  • Slower: takes 5 -7 days to grow and is technically difficult

What antimicrobial therapy would be suitable for Legionella Pneumophila?

As this patient has severe respiratory failure requiring ICU admission, he requires treatment for high-severity Legionella pneumonia with Azithromycin 500mg IV or Ciprofloxacin 400mg IV q8hourly. Combination therapy with Azithromycin and Ciprofloxacin or with Rifampicin plus Azithromycin or Ciprofloxacin is occasionally used in high-severity cases but has not been shown to improve outcomes. Duration of therapy is generally 7 – 10 days unless the patient is immunocompromised or develops complications.

What are the public health implications of Legionella infection in your patient?

Legionella is a notifiable disease requiring the public health unit’s notification. They will then interview the patient (and/or relative) about possible exposures. If two cases are linked by time and place than sources of infection are assessed.