Abstract
Evidence before this study
Vascular pythiosis is a rare, life-threatening disease and all patients with residual disease after surgery died regardless of adjunctive use of antimicrobial agents. Thus, radical surgery has been the mainstay therapy and surgery with achieving negative surgical margins was the main predictor for survival. Recent study revealed that all patients with persistently elevated serum β-d-glucan (BDG) after surgery developed relapsed disease and died despite documented negative surgical margins on pathology. Hence, serum BDG has been used as a monitoring but is limited by availability and prohibitive cost in regions most often affected. In Thailand,itraconazole and terbinafine had been used as the backbone antimicrobial agents, but use was based solely on anecdotal data. Recent in vitro evidence based on susceptibility data from Thai P. insidiosum isolates with favorable minimum inhibitory concentrations (MICs) of tetracyclines and macrolides demonstrated effectiveness of antibiotic therapy in treating pythiosis. Thus,azithromycin, doxycycline, and itraconazole have become the preferred antimicrobial agents under the King Chulalongkorn Memorial Hospital (KCMH) research protocols.
Added value of this study
This study is a clinical trial testing a new treatment regimen consisting of azithromycin,doxycycline, itraconazole, and surgery. The study included a total of 51 patients, divided into 19 patients with residual disease and 32 patients without residual disease. In the group of patients with residual disease, there was an observed increase in survival rates compared to previous treatments using itraconazole and terbinafine, where all patients with residual disease would die within 3 months. The new treatment regimen found that some patients with residual disease survived beyond 3 months, particularly in those who received azithromycin and doxycycline as part of their treatment. Studies on pathogen susceptibility revealed that Pythium insidiosum is sensitive to azithromycin and doxycycline. Additionally, it was found that the tetracyclines and macrolides classes of antibiotics have a synergistic effect.
These findings demonstrate that the new treatment regimen can significantly improve survival rates and reduce mortality in patients with pythiosis. The inclusion of azithromycin and doxycycline in place of terbinafine allows patients with residual disease to survive beyond 3 months, representing a significant treatment success that should be considered in future treatment guidelines.
