Approach

The main goals of Legionellapneumonia treatment are eradication of infection and management of complications. Empirical antibiotic therapy targeted for Legionella species should be included in the initial management of severe community-acquired and hospital-acquired pneumonia until a specific microbiological diagnosis is made.[4] Recovery is most likely if the appropriate antibiotics are given early.[59]​ The patient should be closely monitored for complications, such as respiratory failure, parapneumonic effusion, lung abscess, and empyema. Patients who show signs of deterioration should be managed in the intensive care unit (ICU).

Pontiac fever (non-pneumonic legionellosis) usually resolves spontaneously in 3-5 days and there is no role for antimicrobial drugs.[10]

Antibiotic therapy

An antibiotic that has intracellular activity is required because Legionella survive and replicate within cells.[60][61]​​ Using an antibiotic with activity against atypical bacteria (including Legionella) is recommended by the Infectious Diseases Society of America/American Thoracic Society (IDSA/ATS) in all patients at the time of diagnosis of community-acquired pneumonia (CAP), before a causative pathogen is known.[54][62]​​ However, there is no international consensus for this approach. The British Thoracic Society (BTS) and UK National Institute for Health and Care Excellence (NICE) guidelines reserve use of agents that target atypical pathogens for patients with moderate to severe CAP or when Legionella infection is suspected based on clinical and/or epidemiological features.[63][64][65]​​[66]

The patient should be treated with a fluoroquinolone, such as levofloxacin, or a newer macrolide, such as azithromycin or clarithromycin.[67] Erythromycin was used in early outbreaks and noted to be better than beta-lactam antibiotics (e.g., penicillins) but has been superseded by the newer macrolides and levofloxacin.[68] Observational studies have shown improved outcomes in patients receiving levofloxacin as opposed to erythromycin or clarithromycin, but others found them to be equivocal.[69][70][71]

The annotated British Thoracic Society guidelines for CAP in 2015 favour use of a fluoroquinolone.[65] If there is a known patient allergy to these drugs, or they are not available, then a tetracycline may be tried.

Systemic fluoroquinolone antibiotics may cause serious, disabling, and potentially long-lasting or irreversible adverse events. These include, but is not limited to: tendinopathy/tendon rupture; peripheral neuropathy; arthropathy/arthralgia; aortic aneurysm and dissection; heart valve regurgitation; dysglycaemia; and central nervous system effects including seizures, depression, psychosis, and suicidal thoughts and behaviour.[72]​ Prescribing restrictions apply to the use of fluoroquinolones, and these restrictions may vary between countries. In general, fluoroquinolones should be restricted for use in serious, life-threatening bacterial infections only. Some regulatory agencies may also recommend that they must only be used in situations where other antibiotics, that are commonly recommended for the infection, are inappropriate (e.g., resistance, contraindications, treatment failure, unavailability). Consult your local guidelines and drug formulary for more information on suitability, contraindications, and precautions.

The dose and route of administration of treatment (oral versus intravenous) is guided by severity, underlying risk factors, consciousness level, and gastrointestinal disorders.[4]

The recommendations from the IDSA/ATS guidelines for CAP treatment may be applied to patients with Legionnaires' disease in that, when a patient is clinically stable, intravenous therapy may be changed to oral therapy, followed by patient discharge.[54]

No response to initial therapy or severely ill

Patients with persistent fever, productive cough, hypoxia, hypercapnia, worsening pulmonary function, and systemic signs of sepsis with hypotension may benefit from a combination of fluoroquinolone and macrolide therapy.[73] However, caution is recommended as this combination has significant potential toxicity, such as prolongation of the QT interval and torsades de pointes arrhythmia.[74] Combination therapy with a macrolide or quinolone plus rifamycins (rifampin, rifampicin) has been studied, but is not advocated, even in severe cases, due to poorer outcomes. This is likely related to induction of liver metabolism of the macrolide or quinolone by the rifamycin.[75]

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