A Case Report: Synergistic Benefit of Levofloxacin-Azithromycin Combination Therapy in Severe Legionella Pneumonia

Abstract

Background Studies have shown no significant difference between fluoroquinolone versus macrolide use in reducing mortality in patients with Legionella pneumonia. However, the effects of using both antibiotics simultaneously are not well elucidated. A study analyzing in vitro synergy reported significant synergy for clarithromycin-levofloxacin and azithromycin-levofloxacin against Legionella strains, and with similar findings in other in vitro studies, combination therapy has been suggested to enhance bactericidal activity in severe cases of Legionella. Case description A 58-year-old female presented to ED for worsening shortness of breath, productive cough, and diarrhea. CXR showed multifocal airspace disease, concerning for multifocal pneumonia. Azithromycin and ceftriaxone were started and switched to vancomycin and piperacillin/tazobactam. BMP revealed hyponatremia and urine legionella antigen came back positive. Azithromycin was restarted while the other empiric antibiotics were discontinued. Repeat CXR showed worsening infiltrates, ARDS criteria were met, and intubation was performed due to increased oxygen requirements. Without significant improvement with azithromycin, levofloxacin was added. The next day, CXR showed improved infiltrates while the patient began to display signs of clinical stability. Conclusion Observing the patient’s improvement after the addition of levofloxacin to azithromycin, we hypothesize a synergistic relationship between the antibiotic pair. Prior case studies on severe Legionella pneumonia have likewise demonstrated the efficacy of combination therapy with macrolides plus quinolones as both patients survived. Like the case presented here, combination therapy was successful when monotherapy with levofloxacin or azithromycin failed. Clinical Significance In severe Legionella, physicians should consider macrolide-quinolone dual therapy when macrolide alone initially fails. It is unclear if the patient presented would have survived without adding levofloxacin to the antibiotic regimen.