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Effective antibiotic therapy for legionnaire’s disease is based on anti-Legionella activity and high antibiotic concentrations in alveolar macrophages.
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Antibiotics used for legionnaire’s disease include doxycycline, quinolones, and azithromycin. Alternately, tigecycline, trimethoprim-sulfamethoxazole, and rifamycin are also effective in legionnaire’s disease.
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Legionnaire’s disease outcomes depend not only on effective anti-Legionella therapy but also, importantly, on host factors (ie,
Antimicrobial Therapy for Legionnaire’s Disease: Antibiotic Stewardship Implications
Section snippets
Key points
Background
Effective antibiotic therapy against legionnaire’s disease depends on the antibiotic’s degree of anti-Legionella activity and ability to concentrate in alveolar macrophages (AMs), the primary site of infection in the lung in legionnaire’s disease.1, 2, 3, 4, 5, 6, 7, 8, 9, 10 Antibiotics with anti-Legionella activity that do not penetrate into AMs are clinically ineffective.7, 11, 12 The anti-Legionella antibiotic concentrations in AMs range from 10 to 30 times greater than serum concentrations.
Pharmacokinetic considerations
Historically, optimal monotherapy for legionnaire’s disease has been with doxycycline, a quinolone, or azithromycin.16, 19, 20, 22, 32 Therapeutic failures have been related to host factors.34, 35 Particularly in severe cases, rifampin or TMP-SMX have been used in combination with another anti-Legionella antibiotic.36 However, taking into account the multiple factors previously mentioned, combination therapy in legionnaire’s disease has no proven advantage over well-chosen monotherapy (eg,
Antibiotic stewardship considerations
In CAPs, if the diagnosis of legionnaire’s disease is highly likely or proven, early monotherapy with doxycycline, azithromycin, or a quinolone provides optimal legionnaire’s disease therapy.11, 12, 50 Reasons to not add another antibiotic to the regimen in legionnaire’s disease patients include worsening infiltrates on chest radiograph (CXR), volume depletion, abdominal pain, acute renal failure, or persistent fevers (during the first week of therapy). Because there is no acquired resistance
Community-acquired pneumonia combination therapy versus monotherapy
In practice, therapeutic decisions regarding anti-Legionella coverage relate to 2 clinical considerations. First, if the diagnosis of legionnaire’s disease is most likely clinically based on characteristic clinical findings in legionnaire’s disease, then monotherapy with doxycycline, azithromycin, or a quinolone are optimal regardless of legionnaire’s disease severity.50, 63 Second, the more common clinical scenario is that of CAP of unknown cause and the decision is whether to add an anti-
Summary
Therefore, if several clinical predictors are present and suspicion of legionnaire’s disease is high, doxycycline, azithromycin, or a respiratory quinolone provides optimal empiric monotherapy. Early IV-to-oral switch completes 2 weeks of therapy for normal hosts and 3 weeks of therapy for those with impaired CMI with legionnaire’s disease. Not all CAP cases should be tested for legionnaire’s disease. Only patients with characteristic findings of legionnaire’s disease (ie, clinical predictors)
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