BACKGROUND: Streptococcus suis is an emerging pathogen causing invasive zoonotic infections in humans. Antimicrobial resistance (AMR) to penicillin, macrolides, and tetracyclines has emerged in S. suis-infected swine. AMR among zoonotic S. suis strains causes a critical concern for human infection and antimicrobial treatment options. Thus, the study aims to delineate the clinical characteristics and to explore the changing pattern of the antimicrobial susceptibility (AST) of S. suis infection in humans. METHODS: We conducted a chart review of adult patients with culture-confirmed S. suis infection in any body sites at Siriraj Hospital, Bangkok, Thailand, between May 2007 and May 2023. We also reviewed the AST profile of S. suis isolates during the study period. RESULTS: Over 16 years, 86 adult patients with S. suis infection were identified (59.3% male, mean age 59.29 ± 14.46 years). Of them, 60.5% had comorbidities (hypertension 43%, dyslipidemia 23.3%, diabetes mellitus 20.9%, alcoholism 19.8%), and 35.0% had swine contact a median of 1 (0.0-6.5) days before onset. Clinical presentations included septicemia (91.9%), meningitis (30.2%), endocarditis (26.7%), and septic arthritis (9.3%), leading to multiorgan dysfunction (32.5%), cardiopulmonary failure (26.8%), renal failure (17.4%), and septic shock (14.0%). Mortality was 7%. Definitive therapy primarily used ceftriaxone (76.7%) or penicillin (8.1%) as a basis regimen. Among S. suis isolates tested, 48.2% were susceptible to penicillin (median MIC 0.064 [0.047‒0.094] µg/mL), 96.5% were susceptible to ceftriaxone (median MIC 0.380 [0.110‒0.500] µg/mL), and susceptibility to vancomycin, ofloxacin, tetracyclines, and clindamycin was 100%, 96.4%, 4.8%, and 1.2%, respectively. Penicillin MICs increased significantly (p <
0.002), while other agents' profiles remained stable. CONCLUSIONS: S. suis can cause severe human infection, leading to fatal complications. S. suis displayed an upward trend of penicillin MICs and resistance to several antimicrobial agents. These findings underscore the need to monitor emerging resistance.