M1.2 Human pythiosis

Abstract

Meet the expert session, September 22, 2022, 8:00 AM - 9:00 AMHuman pythiosis is a rare, life-threatening infection, which is generally caused by Pythium insidiosum, a fungal-like oomycete. Four forms of human pythiosis are described: 1) vascular pythiosis affecting the patient's arteries causing arteritis, thrombosis, and gangrene; 2) ocular pythiosis, mainly causing infections of the cornea; 3) skin and soft tissue infections (cutaneous and subcutaneous pythiosis); and 4) disseminated pythiosis. Vascular pythiosis is associated with high morbidity and has a mortality rate of 10%-40%, which attributes to difficulties in diagnosis of the infection and the lack of effective standard treatment. Rice farmers and patients with thalassemia are at risk for vascular infection. Early diagnosis of Pythium infection requires a high index of clinical suspicion and is essential for good treatment results. Microscopic morphology of Pythium spp. resembles other non-septate hyphae, such as agents of mucormycosis. Definite laboratory diagnosis includes tissue cultivation with zoospore induction, polymerase chain reaction (PCR), and detection of Pythium antibodies. Radical surgery together with immunotherapy, and anti-fungal agents (e.g., terbinafine and itraconazole) have previously been used for the treatment of human pythiosis. However, patients with incomplete surgical resection had almost 100% mortality. A novel therapeutic approach and reliable biomarkers are needed to improve patient outcomes. There are several studies demonstrating excellent in vitro activity of antibacterial agents, especially macrolides, tetracyclines, and oxazolidinone against P. insidiosum. There are also evidences of synergy among antibacterial classes such as tetracyclines and macrolides. In 2019, Susaengrat, et al. reported successful treatment of two patients, who had inoperable intra-abdominal vascular pythiosis, with adjunctive antibacterial agents as salvage therapy. The medications included itraconazole in combination with doxycycline and azithromycin or clarithromycin. This case report also confirmed the result of a previous study by Worasilchai, et al. (2018) that serum 1,3-beta-D-glucan (BDG) is useful for monitoring disease activity. The ongoing multicenter prospective study is conducted to evaluate the use of antibacterial agents (azithromycin and doxycycline) with itraconazole and surgery in vascular pythiosis and to evaluate the alternative markers such as erythrocyte sedimentation rate (ESR) and c-reactive protein (CRP). Torvorapanit, et al. (2021) reported preliminary results of 10 patients, which demonstrated favorable outcomes. It was shown that 2/4 patients with the residual disease could successfully be treated with mediations. ESR and CRP declined over time after treatment and Spearman's correlation between ESR and BDG was 0.65, and between CRP and BDG was 0.6. The study aims to recruit 50 patients, which should attest the usefulness of antibacterial agents and these markers in patients with vascular pythiosis.