Antimicrobial Strategies in the Era of Resistance: It Is Too Early to Give Up Antibiotic Therapy
Abstract
The alarming rise of antimicrobial resistance constitutes a critical global health challenge, threatening the efficacy of conventional antibiotic therapies. Despite this crisis, abandoning antibiotics is premature; instead, a deliberate integration of traditional and emerging antimicrobial approaches is urgently required. The worldwide proliferation of resistant pathogens reflects decades of monotherapy, inadequate stewardship, and the persistent expectation that each new drug class would resolve resistance crises. This review provides a comprehensive overview of the fundamental mechanisms underlying antibiotic action and bacterial resistance, including reduced membrane permeability, efflux pump activity, target modification, and enzymatic inactivation. Building on this foundation, a broad spectrum of innovative antimicrobial strategies designed to complement or enhance antibiotic efficacy was critically examined. These approaches include natural products with intrinsic antimicrobial properties, immunotherapy to modulate host defenses, and antimicrobial photodynamic therapy (aPDT), which utilizes light-activated photosensitizers to generate reactive oxygen species and achieve localized microbial destruction. Notably, aPDT can overcome bacterial resistance, thereby restoring antibiotic effectiveness. Light delivery to infection sites is feasible across nearly all anatomical locations, whether by direct application, fiber optics, or endoscopic methods. Additional promising…
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