Torvorapanit P.Worasilchai N.Manothummetha K.Srisurapanont K.Thongkam A.Langsiri N.Leksuwankun S.Meejun T.Thanakitcharu J.Lerttiendamrong B.Susaengrat N.Chuleerarux N.Siriyakorn N.Watcharasuwanseree S.Suparatanachatpun P.Chayangsu S.Khemla S.Kajeekul R.Wattanasoontornsakul W.Bansong R.Sakulkonkij P.Wongkamhla T.Diewsurin J.Laohasakprasit K.Kongsakpaisal P.Chayapum P.Chindamporn A.Plongla R.Permpalung N.Mahidol University2025-07-282025-07-282025-06-15Clinical Infectious Diseases Vol.80 No.6 (2025) , 1281-128910584838https://repository.li.mahidol.ac.th/handle/20.500.14594/111428Background Vascular pythiosis, caused by Pythium insidiosum, is a life-threatening disease with high mortality rate in patients with residual disease post-surgery. This study evaluated the effectiveness of a combination therapy of surgery, azithromycin, doxycycline, and itraconazole. Methods In this open-label, Phase II multicenter trial, 51 patients were enrolled. Patients were categorized based on residual disease post-surgery (unresectable lesions, incomplete resection, or persistent symptoms). Patients with residual disease received azithromycin (500 mg daily), doxycycline (100 mg twice daily), and itraconazole (200 mg thrice daily) until beta-d-glucan (BDG) levels were negative (<80 pg/mL) for 3 months. Those without residual disease received the same regimen for 6 months. Outcomes included all-cause mortality at 6 months, adverse events, changes in BDG levels over time, and factors associated with residual disease and mortality. Results At 6 months, the all-cause mortality rate was 15.7%. Mortality in patients with residual disease was 31.5% compared to 6.25% for those without (P =. 04). Lesions above the popliteal artery were a significant predictor of residual disease (incidence rate ratio [IRR] 3.20, 95% confidence interval [CI]: 1.08-11.70). BDG levels decreased over time (odds ratio [OR] 0.82, 95% CI:. 77-.88 per week, P <. 001) but remained higher in the residual disease group (OR 4.29, 95% CI: 1.55-11.92) Conclusions The combination therapy of surgery, azithromycin, doxycycline, and itraconazole improves survival in patients with vascular pythiosis, including those with residual disease. This regimen is well tolerated and should be considered a standard of care, with further research needed for long-term outcomes.MedicineArticleSCOPUS10.1093/cid/ciaf0622-s2.0-1050112445371537659139932261