Escherichia coli is responsible for diseases of varying severity. The “K” antigen designates the capsular polysaccharides on the bacterial surface, which are mostly similar to those of highly pathogenic bacteria. The K1 antigen is often found in pathogenic E. coli. Aim: While the published studies on the AST profile of K1-positive E. coli have focused on pregnant women or newborns, this study aimed to characterize the AST profile of K1-positive E. coli independently of the clinical sample of isolation. Over a 4-week-long period, all patients hospitalized/consulting at the Poitiers University Hospital presenting a determined AST on E. coli were prospectively included to define their K1-status (Pastorex Meningitis) and to collect the clinical (age/sex) or biological metadata (AST/MIC). Among the 296 included samples, no differential representation was observed between K1 results regarding sample nature. K1-negative results were associated with multiple antibiotic-resistance (12.3% vs. 33.0%; p < 0.01). AST phenotypes differed between these groups, with a higher proportion of K1-negativity among resistant strains, especially on β-lactams (ureidopenicillin, 25.8% vs. 14.9%; and ampicillin/inhibitor, 50.0% vs. 26.8%; p < 0.05) or quinolone (19.8% vs. 7.0%) and sulfamethoxazole-trimethoprim (30.2% vs. 12.3%) (p < 0.01). This study analyzed E. coli ASTs in clinical samples of all types, regarding their K1-antigen status.