Antimicrobial-resistance in clinically harmful bacteria contaminating household drinking water in Eastern Uganda highlights urgent need for enhanced antibiotic resistance stewardship.

Antimicrobial resistance (AMR) is escalating especially in waterborne bacteria, feared to cause over ten-million annual global deaths by 2050. In Eastern Uganda, bacterial contamination of household drinking water containers and sources such as boreholes is increasingly reported, but data on related AMR and contamination enables are scarce, complicating redress. On 260 random water samples, conventional culture and Kirby-Bauer disk diffusion assays were applied at Makerere University. Pre-validated semi structured questionnaires aided studying the contamination enablers. Thematic synthesis, descriptive and inferential statistics (p < 0.05), were used to analyze data, with STATA version-15. Bacterial (167 isolates), representing eleven species were obtained from 41.2% of samples (mainly from jerricans), mostly Escherichia coli (N = 47, 28.1%), and Klebsiella spp (N = 34, 20.4%). Over 59 (49.2%) of isolates were resistant to at least one high-powered drug; 34% were multi-drug resistant. E. coli showed highest resistance to Cefoxitin (48%), K. pneumoniae to Ceftazidime (28%), and Salmonella spp to Nalidixic acid (70%). Contamination enablers emerged in seven themes, the largest being type of water source (N = 11), and sociodemographic (N = 7). Hence, this water is largely unsafe, and some of these bacteria are associated with persistent epidemics, including typhoid fever in Eastern Uganda, warranting concerted efforts to avert the burden.