TABLE 2.

Overview of alternatives to current antibiotics discussed in this review.

Class	Examples	Mode of action	Effective against	Clinical trial stage	Link
Novel antibiotics	Gepotidacin (GSK2140944, Glaxo SmithKlein, UK)	Synthetic drug, triazaacenaphtylene bacterial topoisomerase inhibitors	UTI and urogenital gonorrhea (Neisseria gonorrhoeae)	Phase III	https://www.gsk.com/en-gb/media/press-releases/gsk-starts-a-phase-iii-clinical-programme-for-a-potential-first-in-class-antibiotic-gepotidacin/
	Murepavadin (Polyphor AG, Switzerland)	Synthetic peptidomimetic drug, targets bacteria outer membrane protein	Cystic fybrosis (Pseudomonas aeruginosa)	Phase I (after discontinued Phase III for intravenous formulation)	https://www.polyphor.com/pol7080/
Antimicrobial resistance inhibitors	Beta-lactamase inhibitors	Inhibit serine beta-lactamase enzymes	ESKAPE pathogens	Approved	Ma et al. (2020)
	Efflux pump inhibitors	Prevent removal of antibiotic from the bacterial cell	ESKAPE pathogens	Preclinical tests	Sharma et al. (2019)
Bacteriocins	Nisin	Generates pores in the cell membrane	ESKAPE pathogens; C. difficile	Preclinical tests finished	Dijksteel et al. (2021) and Ma et al. (2020)
	Mersacidin	Inhibits cell wall biosynthesis	MRSA; VRE
	Enterocin	Generates pores in the cell membrane	Salmonella enterica
	NAI-107/NAI-108	Inhibits cell wall biosynthesis	MRSA, VRE, Neisseria gonorrhoeae		Brunati et al. (2018)
Bacteriophages	Biophage-PA	A cocktail of 6 bacteriophages (bacterial viruses) that infect bacteria, replicate in them, and then lyse them in order to infect other surrounding cells	Chronic otitis (P. aeruginosa)	Phase I/II completed	Wright et al. (2009)
	Exebacase (ContraFect, United States)	Bateriophage lysins	Bloodstream infections (S. aureus including MRSA)	Phase II completed	https://www.contrafect.com/pipeline/exebacase
	N-Rephasin (Intron Biotechnology, South Korea)			Phase II	https://intodeworld.com/the-worlds-first-clinical-trial-with-endolysin-based-bio-drug/
Nanoparticles	Silver, gold, copper, zinc, and iron NPs	Generate reactive oxygen species that disrupts membranes, inhibit cytochromes, destabilize ribosomes, damage DNA	Salmonella typhi, S. aureus (including MRSA), E. coli, P. aeruginosa, S. enterica, K. pneumoniae	Preclinical	Fatima et al. (2020)
Sequence-specific antimicrobials	Eligobiotics (Eligo Bioscience, France)	CRISPR-Cas based system; if DNA contains sites homologous to a guide RNA, the system becomes activated and DNA is fragmented by CRISPR-Cas nuclease	ESBL-E. coli; can be tailored to specific bacteria or AMR gene	Preclinical	https://anr.fr/Project-ANR-16-CE18-0021
Anti-virulence drugs	Essential oils of cinnamon, clove, thyme, marjoram	Inhibits quorum sensing mechanisms and thus prevents expression of virulence/pathogenic factors	ESKAPE pathogens	Preclinical	Alibi et al. (2020)
	Nanoparticles				Ali et al. (2020)
	Bacteriocins				Melian et al. (2019)
	Monoclonal antibodies		ESKAPE pathogens; C. difficile; B. Anthracis	Preclinical & clinical Phase I/II/III; FDA-approved	Zurawski and McLendon (2020)
Vaccination	–	Build up host immunity to a pathogen prior to a host encounter with that pathogen	E. coli, S. aureus, P. aeruginosa, and K. pneumoniae	Preclinical & clinical Phase I/II	Ma et al. (2020)