Outcomes of patients with suspected or confirmed melioidosis:A prospective multi-national, multicenter, observational study.

BACKGROUND: Melioidosis is an infectious disease caused by the Gram-negative bacterium Burkholderia pseudomallei. The disease is difficult to diagnose and treat. Here, we investigated outcomes of patients with suspected or confirmed melioidosis in Laos and Thailand. METHODOLOGY: We conducted a prospective, multinational, multicenter, observational study at Mahosot Hospital (MH) in Laos, and Srinagarind Hospital (SRH) and Sunpasitthiprasong Hospital (SUH) in Thailand. We enrolled adult patients (age ≥ 18 years) with suspected or confirmed melioidosis. For suspected-melioidosis cases, patients who had septic shock, had sepsis with at least one risk factor associated with melioidosis (including diabetes mellitus, chronic kidney disease, thalassemia major, malignancy and immunosuppressive therapy) or were prescribed ceftazidime or meropenem by attending physicians were enrolled, provided they were within 24 hours of hospitalization at the study hospitals. For confirmed-melioidosis cases, patients who had a clinical specimen tested positive for B. pseudomallei by either culture or antigen-detecting immunofluorescence microscopy were enrolled. The primary endpoints were 28-day and 90-day mortality. PRINCIPAL FINDINGS: From November 2023 to October 2024, 627 patients were screened and 200 patients were enrolled (43 for suspected-melioidosis and 157 for confirmed-melioidosis). Five of 43 patients enrolled with suspected-melioidosis (12%) were subsequently diagnosed with culture-confirmed melioidosis since enrollment. 28-day and 90-day mortality were 14% (6/43) and 23% (10/43) in suspected-melioidosis patients, respectively; and 25% (39/157) and 36% (57/157) in confirmed-melioidosis patients, respectively. In multivariable Cox regression models, higher Sequential Organ Failure Assessment (SOFA) score at enrollment and intensive care unit (ICU) admission on the day of enrollment were strongly associated with mortality outcomes. Admission to SRH and longer duration of symptoms prior to enrollment were independently associated with survival outcomes. CONCLUSIONS: Future clinical trials aiming to reduce mortality in patients with suspected or confirmed melioidosis should consider stratification based on the severity of organ dysfunction at enrollment. Differences in mortality between study sites may reflect residual confounding and should be carefully considered in sample size calculations.