Abstract: The increasingly severe issue of bacterial multidrug resistance has made restoring the susceptibility of multidrug-resistant strains to the classic aminoglycoside antibiotic amikacin an urgent priority in current research on antimicrobial potentiation. This study focused on a high-risk subtype within stationary-phase multidrug-resistant Klebsiella pneumoniae, namely carbapenem-resistant Klebsiella pneumoniae（CRKP). Using ultrapure water to establish a low-ion environment and 0.9% NaCl as a physiological osmotic pressure control, we conducted drug concentration gradient and time-kill assays, and verified the broad-spectrum bactericidal effect of this strategy across multiple clinical CRKP isolates. The results demonstrated that Hypoionic Shock significantly enhanced the bactericidal activity of amikacin against clinical multidrug-resistant Klebsiella pneumoniae, with a concentration-dependent potentiation effect; this effect was also applicable to gentamicin and tobramycin. These findings provide a novel in vitro research approach for the prevention and control of clinical multidrug-resistant Gram-negative bacteria, and also suggest that simply adjusting the ionic strength of the administration environment may enhance the therapeutic efficacy of existing aminoglycoside antibiotics in local infections（such as urinary tract infections and intra-abdominal infections), offering a simple and feasible adjunctive strategy for delaying the emergence of antimicrobial resistance.