Antibiotic adjuvants against multidrug-resistant Gram-negative bacteria: important component of future antimicrobial therapy

The swift emergence and propagation of multidrug-resistant (MDR) bacterial pathogens constitute a tremendous global health crisis. Among these pathogens, the challenge of antibiotic resistance in Gram-negative bacteria is particularly pressing due to their distinctive structure, such as highly impermeable outer membrane, overexpressed efflux pumps, and mutations. Several strategies have been documented to combat MDR Gram-negative bacteria, including the structural modification of existing antibiotics, the development of antimicrobial adjuvants, and research on novel targets that MDR bacteria are sensitive to. Drugs functioning as adjuvants to mitigate resistance to existing antibiotics may play a pivotal role in future antibacterial therapy strategies. In this review, we provide a brief overview of potential antibacterial adjuvants against Gram-negative bacteria and their mechanisms of action, and discuss the application prospects and potential for bacterial resistance to these adjuvants, along with strategies to reduce this risk. [Display omitted] •Critical-priority Gram-negative bacteria on the WHO Bacterial Priority Pathogens List are a serious health concern.•The spread of the resistant gene tet(X3)/tet(X4) makes Tigecycline with adjunctive therapy an indispensable strategy.•Utilizing nutritional immune strategies to restrict bacterial iron uptake presents a novel adjuvant concept.•Lactobacillus plantarum as "Postbioticst" enhanced the antibiofilm effect of tobramycin.•β-lactam antibiotics/β-lactamase inhibitors are promising antibiotic-adjuvant combinations for future antimicrobial therapy.