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

Abstract

Case description A 58-year-old female presented to ED for worsening shortness of breath x1 week. She was also reported to have a productive cough and diarrhea. CXR upon arrival showed multifocal airspace disease, concerning for multifocal pneumonia. Azithromycin and ceftriaxone were started and switched to vancomycin and piperacillin/tazobactam. BMP revealed hyponatremia, and not surprisingly, urine legionella antigen came back positive. Azithromycin was then restarted while ceftriaxone, vancomycin, and piperacillin/tazobactam were all discontinued. Repeat CXR continued to show worsening infiltrates. Intubation was performed as ARDS criteria was met with unchanged infiltrates and increasing 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. Both patients in the documented cases survived. Similar to the case presented, combination therapy was found to be successful when monotherapy with levofloxacin or azithromycin failed. In a separate study analyzing in vitro synergy, erythromycin, clarithromycin, and azithromycin, each in combination with ciprofloxacin and levofloxacin were tested against 41 isolates of Legionella. Significant synergy was reported for the clarithromycin- levofloxacin and azithromycin-levofloxacin combinations, acknowledging the enhanced effect of using these antibiotics simultaneously. Clinical Significance In severe Legionella, physicians ought to consider macrolide-quinolone dual therapy when levofloxacin or azithromycin alone initially fails. It is unclear if the patient presented survives without both levofloxacin and azithromycin.