Monoclonal Antibodies as Precision Adjuncts in the Era of Antimicrobial Resistance

Antimicrobial resistance has created an urgent need for therapeutic strategies that complement the increasingly limited antibiotic armamentarium against multidrug-resistant (MDR) bacterial pathogens. Monoclonal antibodies (mAbs) offer a mechanistically distinct approach by targeting bacterial virulence factors, toxins, surface antigens, secretion systems and biofilm-associated pathways rather than conventional antimicrobial targets. Preclinical studies and early clinical trials have demonstrated biological activity, particularly against Pseudomonas aeruginosa and Staphylococcus aureus , but clinical efficacy has remained inconsistent. Key barriers include antigenic heterogeneity, target accessibility, biofilm-associated protection, disease timing, tissue penetration and dependence on host immune function. Importantly, most clinical programmes have not been designed specifically around MDR populations, leaving their role in resistant infections incompletely defined. Future development should prioritise conserved and accessible targets, multispecific antibody engineering, optimised Fc function, genomic-guided target selection and biomarker-informed patient selection. Rational combination with antibiotics or other targeted therapies may further enhance efficacy. Rather than replacing antibiotics, mAbs may ultimately serve as precision adjuncts for infections in which conventional antimicrobial therapy is increasingly compromised.