Legionnaires' Disease

Legionnaires' disease is a severe pneumonia caused by Legionella species, most commonly Legionella pneumophila serogroup one. It is acquired by inhaling aerosolised water contaminated with the organism (cooling towers, hot water systems, spa pools, humidifiers).

It is distinguished from other causes of community acquired pneumonia by multisystem involvement and specific epidemiological associations. The organism is intracellular, so it needs specific rather than standard empirical antibiotic therapy.

Pathophysiology and epidemiology

The organism proliferates within environmental water systems, particularly in biofilms and in association with free living amoebae. Humans are infected by inhaling contaminated aerosols, not by person to person transmission.

Once inhaled, the organism is engulfed by alveolar macrophages but survives and replicates intracellularly, evading normal phagocytic killing.

Beta lactam antibiotics do not achieve adequate intracellular concentration and are ineffective. Agents with good intracellular penetration are required.

A prodrome of headache, malaise and myalgia over one to two days precedes the onset of high fever, often with rigors, and a relatively unproductive cough. This differs somewhat from the productive cough typical of pneumococcal pneumonia.

Extrapulmonary features are characteristic and help raise suspicion:

• gastrointestinal symptoms (watery diarrhoea, abdominal pain, nausea), occurring in a substantial proportion and sometimes preceding respiratory symptoms
• confusion and other neurological features, disproportionate to the degree of hypoxia
• relative bradycardia in relation to the degree of fever, a classically described though inconsistently present sign

Hyponatraemia is a characteristic and relatively specific laboratory finding. It reflects a combination of inappropriate antidiuretic hormone secretion and direct renal tubular effects, and should raise suspicion for this pathogen in a patient with pneumonia.

Risk factors include smoking, chronic lung disease, immunosuppression, older age, diabetes, and a relevant exposure history (recent travel with hotel or cruise ship stay, exposure to spa pools, or occupational exposure to cooling towers or water systems).

Urinary antigen testing is the most widely used and rapid diagnostic test. It detects Legionella pneumophila serogroup one, which accounts for the large majority of clinical disease, with good sensitivity and specificity.

It does not detect other serogroups or non pneumophila species. Recognise this limitation where clinical suspicion remains high despite a negative result.

Sputum culture on specific selective media (buffered charcoal yeast extract agar) detects all Legionella species and serogroups and permits strain typing for epidemiological investigation. It takes several days and has lower sensitivity than urinary antigen testing in routine practice.

Polymerase chain reaction on respiratory specimens offers rapid, sensitive detection across species and serogroups where available. Paired serology (acute and convalescent, four to six weeks apart) can retrospectively confirm the diagnosis where other testing has been negative or unavailable.

Chest radiography shows non specific patchy or lobar consolidation, often more extensive than the clinical picture suggests. No radiographic feature distinguishes it from other causes of bacterial pneumonia.

Fluoroquinolones are first line treatment, given excellent intracellular penetration and clinical outcome data.

• Levofloxacin 750 mg once daily (intravenous or oral).
• Ciprofloxacin 400 mg intravenously twice daily (or 750 mg orally twice daily).
• Use the intravenous route for more severe disease, then transition to oral therapy once clinically stable.

Macrolides are an effective alternative, particularly azithromycin 500 mg once daily (intravenous or oral). Its long tissue half life means a shorter course is typically needed. Older macrolides such as erythromycin are now rarely used because of a less favourable adverse effect and interaction profile.

Beta lactam antibiotics, including penicillins and cephalosporins, are ineffective because of inadequate intracellular penetration. Do not rely on them as monotherapy, even where a broad spectrum agent might otherwise seem reasonable for pneumonia of unclear cause.

Duration of treatment:

• 7 to 10 days with a fluoroquinolone, or 5 days with azithromycin, for mild to moderate disease.
• 10 to 14 days (or longer, up to 21 days) for severe disease, immunocompromised hosts, or slow clinical response.

Combination therapy (fluoroquinolone plus a macrolide) is reserved for the most severe or immunocompromised presentations. Rifampicin was historically considered but is now rarely added, given limited evidence of additional benefit.

Supportive care follows standard severe pneumonia principles. It includes supplemental oxygen, careful fluid management given the propensity for hyponatraemia and the risk of both under and over correction, and escalation to intensive care for respiratory failure or septic shock.

Notify public health authorities, given the potential for a point source outbreak. Environmental investigation of the likely exposure source (recent travel accommodation, occupational water systems) is an important measure to prevent further cases.