374. A Multicenter Open-Label Single-Arm Clinical Trial of Combination Therapy of Surgery, Itraconazole, Doxycycline, and Azithromycin for Vascular Pythiosis
Authors: Manothummetha Kasama , Torvorapanit Pattama , Susaengrat Nuttapon , Worasilchai Navaporn , Chindamporn Ariya , Chuleerarux Nipat , Bansong Ratiporn , Wattanasoontornsakul Watchara , Oranrigsupak Petchdee , Diewsurin Jaruwan , Payoong Paruspak Paruspak , Kongsakpaisan Prasopchai , Wangsapthawi Ginthasuphang , Siriyakorn Nirada , Thongkam Achitpol , Watcharasuwanseree Sureerat , Thanakitcharu Jaedvara , Leksuwankun Surachai , Meejun Tanaporn , Phongkhun Kasidis , Langsiri Nattapong , Sakulkonkij Parichart , Chayangsu Sunee , Laohasakprasit Kanokwan , Lerttiendamrong Bhoowit , Khemla Supphachoke , Srisurapanont Karan , Kajeekul Rattagan , Chayapum Poom , Plongla Rongpong , Permpalung Nitipong 
Published: November 2023

Abstract

Background
Vascular pythiosis, caused by Pythium insidiosum, is a neglected, life-threatening condition which carried a 100% mortality rate, within 3 months, among patients with residual disease after surgery, regardless of antifungal treatment. Recently, Thai P. insidiosum isolates were found to susceptible to doxycycline and azithromycin, with evidence of synergy. We report results of a clinical trial from 15 centers in Thailand (Thai Clinical Trial Registry number TCTR20191217006).

Methods
This study enrolled patients with vascular pythiosis who had 2 of the 4 diagnostic criteria: consistent clinical presentation, positive serum P. insidiosum-specific antibodies, positive cultures, or positive histopathology. All received surgery, itraconazole, doxycycline, and azithromycin. Patients were followed up until 6 months after diagnosis. Subsequent follow-ups after 6 months were at the clinician’s discretion if there were any concerns for residual diseases or unresectable arterial lesions.

Results
40 patients were enrolled, with a median age (interquartile range [IQR]) of 51 (45-56) years. 38 (95%) had major thalassemia, 1 (2.5%) had liver cirrhosis, and 1 (2.5%) had myeloproliferative syndrome. None had known immunocompromised conditions. After surgery, 14 (35%) still had residual diseases. At 6 months after diagnosis, 3 (7.5%) patients died (disseminated pythiosis, sepsis with multi-organ failure, and ESBL Klebsiella pneumoniae bacteremia). Among patients with residual disease, 1 (7.1%) died and 13 are still alive. Median follow-up time (IQR) among patients with residual disease was 385 (209-622) days. There were no statistical differences in time from onset to surgery and time from onset to first antimicrobial between patients with and without residual disease after surgery (Table). One patient had to stop doxycycline prematurely due to photosensitivity.
Patient characteristics
IQR: interquartile range; N: number

Conclusion
The new treatment combination with surgery, itraconazole, azithromycin, and doxycycline improved survival among patients with vascular pythiosis who had residual disease.

Disclosures
Nitipong Permpalung, MD, MPH, Alcimed: Advisor/Consultant|CareDx: Grant/Research Support|Cidara Therapeutics: Grant/Research Support|Clarion: Advisor/Consultant|ClearView: Advisor/Consultant|IMMY Diagnostics: Grant/Research Support|Merck: Grant/Research Support|Scynexis: Grant/Research Support