Key Facts

Atypical pneumonia refers to pneumonia caused by organisms that do not respond to beta-lactam antibiotics and are not identified on standard Gram stain or culture. The term reflects both the unusual clinical presentation (compared to typical lobar pneumonia) and the atypical organisms responsible.

Epidemiology

• Accounts for ~15-25% of all CAP cases
• Mycoplasma pneumoniae: most common; 4-yearly epidemic cycles, mainly affects ages 5-40
• Legionella: ~2-5% of CAP; higher in summer/autumn; travel-associated; outbreaks from cooling towers
• Chlamydophila pneumoniae: ~5-10%; mild illness, common in young adults
• Chlamydophila psittaci: occupational exposure to birds (psittacosis)
• Coxiella burnetii: Q fever; exposure to livestock/farm animals

Aetiology

• Mycoplasma pneumoniae: smallest free-living bacterium; lacks cell wall (hence beta-lactam resistance)
• Legionella pneumophila: Gram-negative rod; contaminated water, cooling towers, spa pools; serogroup 1 most common
• Chlamydophila pneumoniae/psittaci: obligate intracellular; person-to-person (C. pneumoniae) or bird-to-human (C. psittaci)
• Coxiella burnetii: obligate intracellular; livestock, placental tissue; Q fever

Pathophysiology

• Intracellular organisms evade standard immune defences
• Immune-mediated pathology contributes (Mycoplasma: cold agglutinins, autoimmune haemolysis, cross-reactive antibodies)
• Diffuse interstitial rather than alveolar inflammation → patchy bilateral infiltrates
• Extrapulmonary manifestations reflect systemic immune activation

General Atypical Features

• Gradual onset (over days)
• Dry (non-productive) cough
• Prominent systemic symptoms: headache, myalgia, malaise, fever
• Minimal chest signs despite CXR changes ("walking pneumonia")
• Extrapulmonary features common

Mycoplasma pneumoniae

• Young adults (5-40 years), campus/military outbreaks
• Dry cough, headache, malaise
• Extrapulmonary: erythema multiforme/Stevens-Johnson syndrome, cold agglutinins (autoimmune haemolytic anaemia), myocarditis, pericarditis, encephalitis, Guillain-Barré syndrome, arthritis, bullous myringitis

Legionella pneumophila

• Travel, contaminated water, outbreaks
• High fever, rigors, confusion
• Key triad: confusion, hyponatraemia, deranged LFTs
• GI symptoms: diarrhoea, abdominal pain, nausea
• Can cause severe pneumonia requiring ICU

Chlamydophila psittaci

• Bird exposure (parrots, pigeons, poultry workers)
• Pneumonia with hepatosplenomegaly, rash (Horder spots)

Q Fever (Coxiella burnetii)

• Farm/livestock exposure
• Pneumonia, hepatitis, endocarditis (chronic Q fever)

Red Flags

• Severe Legionella pneumonia (CURB-65 ≥3)
• Mycoplasma with neurological complications (encephalitis, GBS)
• Stevens-Johnson syndrome
• Multi-organ involvement
• Non-response to beta-lactam antibiotics

Bedside

• Pulse oximetry: SpO₂
• Urinary Legionella antigen: rapid result (sensitivity ~70-80% for serogroup 1 only)
• Urinary pneumococcal antigen: to identify co-infection
• CURB-65 score: severity assessment

Bloods

• FBC: leucocytosis or normal WCC; lymphopenia (viral); anaemia (cold agglutinins in Mycoplasma)
• CRP: elevated
• U&Es: hyponatraemia (Legionella)
• LFTs: deranged in Legionella, Q fever, psittacosis
• Cold agglutinins: positive in ~50% of Mycoplasma (IgM anti-I)
• Blood cultures x2: exclude typical organisms
• Mycoplasma IgM serology: acute infection
• Legionella PCR on respiratory sample: more sensitive than urinary antigen

Imaging

• CXR: patchy bilateral infiltrates, interstitial pattern, lower lobe predominance; may be worse than clinical signs suggest
• CT chest: ground-glass opacification, tree-in-bud, patchy consolidation

Special Tests

• Legionella culture (BCYE agar): takes 3-5 days; gold standard
• Mycoplasma PCR (throat swab/sputum): rapid, sensitive
• Paired serology (acute and convalescent, 2-4 weeks apart): 4-fold rise in titre confirms diagnosis
• Complement fixation tests: Mycoplasma, Chlamydophila, Q fever
• Bronchoscopy/BAL: if diagnostic uncertainty or immunocompromised

Non-pharmacological

• Oxygen therapy as needed
• IV fluids if dehydrated
• Isolate if Legionella suspected (prevent nosocomial spread from water systems)
• Notify PHE: Legionella, Q fever, psittacosis are notifiable diseases

Pharmacological

First-line antibiotics (atypical coverage):

• Clarithromycin 500mg BD PO/IV for 7-14 days (most atypicals)
• Or doxycycline 200mg loading then 100mg OD for 7-14 days

Severe Legionella:

• Levofloxacin 500mg OD/BD IV or azithromycin 500mg OD IV
• Consider adding rifampicin 600mg BD in severe/ICU cases
• Duration: 14-21 days

Mycoplasma pneumoniae:

• Clarithromycin 500mg BD or doxycycline 100mg BD for 7-14 days
• Severe/neurological: consider IV clarithromycin or azithromycin
• Corticosteroids for severe immune-mediated complications (encephalitis, SJS)

Chlamydophila/Psittacosis:

• Doxycycline 100mg BD for 14 days (first-line)
• Alternative: clarithromycin

Q Fever:

• Acute: doxycycline 100mg BD for 14 days
• Chronic (endocarditis): doxycycline + hydroxychloroquine for ≥18 months

Surgical/Interventional

• Not typically required
• Drain empyema if present

Referral Criteria

• PHE notification for Legionella, psittacosis, Q fever
• ICU for severe Legionella
• Infectious diseases for complex cases or chronic Q fever
• Environmental health investigation for Legionella outbreaks

• Mycoplasma pneumonia: usually self-limiting; mortality <1%; complications in 5-10%
• Legionella: mortality ~5-10% (up to 30% in immunocompromised or ICU)
• Psittacosis: mortality <1% with treatment; rarely fatal
• Q fever: acute infection usually self-limiting; chronic Q fever endocarditis has significant morbidity
• Overall atypical pneumonia has good prognosis with appropriate antibiotic therapy
• Neurological complications of Mycoplasma (GBS, encephalitis) may cause lasting disability

Atypical Pneumonia Organism Summary

Notifiable Atypical Pneumonia Organisms (UK)