Antimicrobial resistance has escalated into one of the gravest public-health crises of the 21st century.(p1) Multidrug-resistant (MDR) Gram-negative pathogens, such as Pseudomonas aeruginosa, Klebsiella pneumoniae, and Acinetobacter baumannii, now cause >700 000 deaths annually, and projections warn of 10 million casualties per year by 2050 if current trends persist.(p2) Conventional antibiotics are losing efficacy at alarming speed; for example, 30–50% of clinical P. aeruginosa isolates are already resistant to three or more drug classes.(p3) Developing a new antibiotic can take 10–15 years and costs >US$1 billion, yet clinical attrition exceeds 90%, making it economically unattractive for pharmaceutical companies to address the most urgent resistance threats.(p4) Consequently, there is a widening gap between the rapid evolution of resistant pathogens and the slow generation of effective counter-measures.

In this landscape, drug repurposing offers a pragmatic alternative. The transition metal gallium (Ga3+), already US Food and Drug Administration (FDA) approved for intravenous use in hypercalcemia, is able to disrupt bacterial iron metabolism and to kill both planktonic and biofilm organisms at micromolar concentrations.(p5) A Phase I/II program in patients with cystic fibrosis with chronic P. aeruginosa lung infection confirmed the safety of gallium nitrate and, although the 2016 Phase II trial (NCT02354859) missed its primary endpoint, gallium nitrate still achieved a significant reduction in sputum P. aeruginosa burden versus placebo.(p6),(p7) Nevertheless, crucial translational questions relating to optimal formulation, pharmacokinetics in infected tissues, synergy with host iron-withholding defences, and resistance risk, remain largely unexplored.(p8) Filling these knowledge gaps could position gallium-based therapeutics as a rapid, cost-effective response to the antibiotic-resistance pandemic. Here, we review recent mechanistic, preclinical, and translational insights into gallium-based antimicrobials, underscoring their potential as a next-generation, resistance-breaking strategy against the escalating global crisis of MDR bacteria.