What is the first line treatment for Legionella (Legionnaires' disease)?

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Last updated: May 24, 2025 • View editorial policy

From the Guidelines

The first-line treatment for Legionella pneumonia is azithromycin or levofloxacin, as recommended by the most recent and highest quality study 1.

Key Points

  • Azithromycin is typically dosed at 500 mg IV or orally on day 1, followed by 250 mg daily for a total of 5-10 days.
  • Levofloxacin is given as 750 mg IV or orally once daily for 7-14 days.
  • For severe infections, some experts recommend combination therapy with both agents.
  • Treatment duration should be extended to 14-21 days in immunocompromised patients or those with severe disease.
  • These antibiotics are preferred because they achieve high intracellular concentrations, which is essential since Legionella is an intracellular pathogen that multiplies within alveolar macrophages, as noted in 2 and 1.

Rationale

The preferred treatment for Legionella pneumonia is based on the ability of azithromycin and levofloxacin to penetrate cells and reach the bacteria, as well as their good lung tissue penetration, as discussed in 3 and 4.

Additional Considerations

  • Clinical improvement typically occurs within 3-5 days of appropriate therapy.
  • The duration of treatment may vary depending on the severity of the disease and the patient's response to therapy, as mentioned in 5.

From the FDA Drug Label

Azithromycin for Injection, USP is indicated for the treatment of patients with infections caused by susceptible strains of the designated microorganisms in the conditions listed below... Community-acquired pneumonia due to Chlamydia pneumoniae, Haemophilus influenzae, Legionella pneumophila, Moraxella catarrhalis, Mycoplasma pneumoniae, Staphylococcus aureus, or Streptococcus pneumoniae in patients who require initial intravenous therapy The first line treatment for Legionella infections is Azithromycin (IV), as it is indicated for the treatment of community-acquired pneumonia due to Legionella pneumophila 6.

From the Research

First-Line Treatment for Legionella

  • The first-line treatment for Legionnaires' disease includes either a fluoroquinolone (levofloxacin or moxifloxacin) or a macrolide (azithromycin preferred) 7, 8, 9.
  • Azithromycin or levofloxacin can be considered as first-line therapy for Legionnaires' disease 9.
  • Other antibiotics including tetracyclines, tigecycline, other fluoroquinolones, and other macrolides (especially clarithromycin) are also effective 9.
  • Macrolides and fluoroquinolones are the recommended treatment for Legionnaires' disease, with similar outcomes 10.

Treatment Options

  • Azithromycin has been shown to be efficacious in animal models and in clinical studies of patients with Legionnaires' disease 11.
  • Clarithromycin, azithromycin, and levofloxacin were all found to be efficacious for the treatment of Legionnaires' disease in a prospective, observational study 10.
  • The clinical response of quinolones may be somewhat more favorable compared to macrolides, but the outcome is similar 9.

Recommendations

  • Antibiotics directed against Legionella spp. should be included early as empirical therapy for severe community-acquired pneumonia 7.
  • Inadequate or delayed antibiotic treatment in Legionella pneumonia has been associated with a worse prognosis 7.
  • The preferred therapy for legionellosis in immunocompromised patients is quinolone/macrolide combinations, such as levofloxacin plus azithromycin 8.

References

Guideline

recommendations and guidelines for the treatment of pneumonia in taiwan.

Journal of Microbiology, Immunology and Infection, 2019

Research

Legionnaires' Disease: Update on Diagnosis and Treatment.

Infectious diseases and therapy, 2022

Research

Treatment of legionnaires' disease.

Seminars in respiratory infections, 1998

Research

Treatment strategies for Legionella infection.

Expert opinion on pharmacotherapy, 2009

Research

[Treatment for Legionnaires' disease. Macrolides or quinolones?].

Enfermedades infecciosas y microbiologia clinica, 2006

Research

Azithromycin in the treatment of Legionella pneumonia requiring hospitalization.

Clinical infectious diseases : an official publication of the Infectious Diseases Society of America, 2003

Professional Medical Disclaimer

This information is intended for healthcare professionals. Any medical decision-making should rely on clinical judgment and independently verified information. The content provided herein does not replace professional discretion and should be considered supplementary to established clinical guidelines. Healthcare providers should verify all information against primary literature and current practice standards before application in patient care. Dr.Oracle assumes no liability for clinical decisions based on this content.