Abstract
The emerging antimicrobial resistance (AMR) poses serious threats to the global public health. Conventional antibiotics have been eclipsed in combating with drug-resistant bacteria. Moreover, the developing and deploying of novel antimicrobial drugs have trudged, as few new antibiotics are being developed over time and even fewer of them can hit the market. Alternative therapeutic strategies to resolve the AMR crisis are urgently required. Pathogen-oriented therapy (POT) springs up as a promising approach in circumventing antibiotic resistance. The tactic underling POT is applying antibacterial compounds or materials directly to infected regions to treat specific bacteria species or strains with goals of improving the drug efficacy and reducing nontargeting and the development of drug resistance. This review exemplifies recent trends in the development of POTs for circumventing AMR, including the adoption of antibiotic-antibiotic conjugates, antimicrobial peptides, therapeutic monoclonal antibodies, nanotechnologies, CRISPR-Cas systems, and microbiota modulations. Employing these alternative approaches alone or in combination shows promising advantages for addressing the growing clinical embarrassment of antibiotics in fighting drug-resistant bacteria.
Highlights
After several decades of successful practices using antibiotics to treat bacterial infectious diseases, the emergence of antimicrobial resistance (AMR) has been recognized as a global public health crisis nowadays [1,2,3,4]
Antibioticresistant bacteria kill 700,000 people/year worldwide, and the annual death toll caused by AMR is expected to be 10 million by 2050, disbursing about $100 trillion globally [5, 6]
Antibiotic-Antibiotic Conjugates (AACs) can be composed of two antibiotics with both of their antimicrobial activity for exerting a synergistic effect, or be composed of antibiotics with their bioactive adjuvants, such as inhibitors of efflux pumps or antibiotic-modifying enzymes, for enhancing the effect of antibiotics and improving their pharmacokinetic parameters
Summary
After several decades of successful practices using antibiotics to treat bacterial infectious diseases, the emergence of antimicrobial resistance (AMR) has been recognized as a global public health crisis nowadays [1,2,3,4]. AAC can be composed of two antibiotics with both of their antimicrobial activity for exerting a synergistic effect, or be composed of antibiotics with their bioactive adjuvants, such as inhibitors of efflux pumps or antibiotic-modifying enzymes, for enhancing the effect of antibiotics and improving their pharmacokinetic parameters Despite these advantages, AAC pays more attention to whether it has superior or at least no inferior antibacterial activity compared with classical combination therapy or parental generation, but most current studies are lack of systematic research on the occurrence and mechanism of drug resistance. Some of the disadvantages of AMP conjugates, including high production cost, low oral bioavailability, poor metabolic stability, and undesirable serum stability and immunogenicity, still need to be further studied before they can be used in vivo This drug delivery strategy is expected to provide new treatment options for the fight against pathogen resistance
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