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Additionally, polystyrene-based resins (PS resins), especially those crosslinked with divinylbenzene (i.e., P(St-DVB) resins), proved to be a good choice as a matrix substrate for disinfect agents such as silver [25], quaternary ammonium salts [26], N-halamine [27], chitosan [28], antimicrobial peptides [29], etc. In this way, materials for the purification of drinking water can be obtained, thanks to the low cost of P(St-DVB) resins, their good mechanical strength, high porosity, and absorbency [25; 26; 27; 28; 29; 30]. In this context, we recently reported the broad-spectrum bactericidal potency of a water-soluble cationic polystyrene-based copolymer (P5) obtained by copolymerizing the 4-ammonium butyl styrene hydrochloride salt (4-ABSTY), synthetized by us and chosen as an active monomer, with di-methyl-acrylamide (DMAA), chosen as the uncharged co-monomer [31]. On these results, aiming to develop a resin intrinsically capable of efficiently reducing the bacterial load in water, without the need for additional antibacterial agents losable during the purification processes, in this study, we synthesized the cationic cross-linked copolymer, namely resin R4, analogous to the water-soluble P5. This was accomplished by a one-step procedure, using the reverse-phase suspension copolymerization technique. In particular, the 4-ABSTY hydrochloride salt (M4 in this work, Figure 1) previously used as an active cationic monomer to obtain the water-soluble copolymer P5 was re-synthesized and copolymerized with DMAA in the presence of AAEA as a cross-linker under opportune conditions, later described, obtaining R4. R4 was fractionated by sieving to achieve a central body of particles (>96% of the total amount subjected to sieving) with little dispersed granulometry, and very homogenous porosity, and first characterized by attenuated-total-reflectance (ATR) Fourier transformed infrared (FTIR) spectroscopy, to assess the presence of all predicted functional groups. Optical microscopy examinations were carried out both on R4, as obtained from polymerization, and on the swollen resin obtained after swelling it to its maximum swelling capability to evaluate its morphology and particle size in both cases, and to estimate its hydrophilicity and swelling capability in water. The water loss and swelling rate over time experiments were also conducted and reported to obtain the water release and absorption profiles. The determination of the maximum swelling capability was also used to confirm its high capacity to absorb water and determine its porosity. The content of NH3+ groups, essential to allow electrostatic interactions with the negatively charged surface of the bacteria and to capture, inhibit, and/or kill them, was determined following the method of [PERSON] and [PERSON] and confirmed using the results obtained by potentiometric titrations. The antibacterial properties of R4 were assessed first by carrying out classical time-kill experiments, exposing several clinical MDR isolates of fecal origin, including strains of _E. coli_, Group B _Salmonella_ species, and species of the genus _Enterococcus_, to R4 for 4 h. Then, the same experiments were conducted on a mixture of strains from each of the previous species to investigate the potential negative or positive impact on the antibacterial efficiency of R4 of the co-existence of more bacterial species. Finally, the optimal contact time between aqueous samples containing a mixture of the same bacteria, which simulated a real contaminated water, and R4 in a hypothetical column disinfection system to have the best decontaminating activity of R4 was assessed.