Emerging CRISPR-Cas, Antibody, and Nanomedicine Strategies Against Antimicrobial Resistance in Critical Care

Abstract

Antimicrobial resistance (AMR) has become one of the defining threats to survival in intensive and neonatal intensive care units, where vulnerable hosts, invasive devices, and heavy empirical antibiotic exposure converge to select for multidrug- and extensively drug-resistant ESKAPE and non-aeruginosa Pseudomonas pathogens. We conducted a narrative-scoping synthesis of the peer-reviewed literature identified through targeted searches and, restricted to English-language articles addressing AMR mechanisms and next-generation, non-traditional therapeutics in critical care; reference lists were hand-searched, and findings were organized thematically rather than statistically pooled. Four convergent, non-traditional pillars emerged — programmable CRISPR-Cas and CRISPRi genomic tools, monoclonal antibodies and bioconjugates, antimicrobial and anticancer peptides (notably proline-rich peptides), and stimuli-responsive nanozymes and exosomal carriers — each capable of bypassing classical resistance mechanisms while, at least in preclinical models, sparing commensal microbiota. Persistent translational barriers include bedside diagnostic blindness to biofilm-embedded organisms, an unresolved neonatal and pediatric pharmacokinetic/pharmacodynamic void, and stewardship frameworks that still largely ignore the human resistome. Bridging bench-to-bedside gaps will require standardized biofilm models, dedicated pediatric PK/PD trials, artificial-intelligence-assisted therapeutic design, and microbiome-conscious stewardship, particularly given resource disparities across low- and middle-income settings.