Table 1.

Antibiotic adjuvants

Mode of action		Adjuvant	Antibiotic	Commercial combination	Reference
Inhibition of vital physiology pathways	Complete inhibition of the folic acid biosynthetic pathway	–	Sulfamethoxazole/Trimethoprim	Septra® and Bactrim®	Reeves (1971)
	Inhibition of the synthesis and repair of the bacterial cell wall	Fosfomycin	Gentamicin, Amikacin, Ceftazidime, Cefepime, Ciprofloxacin, Levofloxacin, and Aztreonam	–	Kastoris et al. (2010)
	Oxidative stress outbreak	Tellurite	Ampicillin, Cefotaxime, Tetracycline, Chloramphenicol, Gentamicin	–	Molina-Quiroz et al. (2012)
	Cell shape alterations	Compound 1, A22, pivmecillinam, and echinomycin	Novobiocin	–	Taylor et al. (2012)
Inhibition of antibiotic resistance elements	β-lactamase inhibitors	Clavulanic acid	Amoxicillin	Augmentin®	Brown et al. (1976); Drawz and Bonomo (2010)
			Ticarcillin	Timentin®	Drawz and Bonomo (2010)
			Meropenem	–	Hugonnet et al. (2009)
		Sulbactam	Ampicillin	Unasyn®	Drawz and Bonomo (2010)
		Tazobactam	Piperacillin	Tazocin® and Zosyn®	Drawz and Bonomo (2010)
	Dehydropeptidase I inhibitor	Cilastatin	Imipenem	Tienam®	Balfour et al. (1996)
Enhance the uptake of the antibiotic through the bacterial membrane	Antibiotics that damage the cell wall improving uptake of other antibiotics	β-lactams, bacitracin, vancomycin, cycloserine	Aminoglycosides (Streptomycin, Gentamicin)	–	Chanbusarakum and Murray (1978); Moellering et al. (1986); Barnes et al. (2005)
	Binds to and interferes with the integrity of the LPS-containing outer membrane layer	Colistin (polymyxin E)	Rifampin or Vancomycin	–	Aoki et al. (2009); Gordon et al. (2010)
	Damages the bacterial membrane	Eugenol (from Eugenia aromatic)	Vancomycin	–	Hemaiswarya and Doble (2009)
		Phenylpropanoids	Amikacin, Ampicillin, Ciprofloxacin, Erythromycin and Vancomycin	–	Hemaiswarya and Doble (2010)
	Permeabilizes the bacterial membrane	Loperamid	Tetracyclines	–	Ejim et al. (2011)
Blocking of efflux pumps	Competitive inhibition	Tretacycline analogues	Tetracyclines	–	Van Bambeke et al. (2010)
		Fluoroquinolone analogues	Fluoroquinolones, Macrolides	–	Van Bambeke et al. (2010)
		Aminoglycoside analogues	Gentamicin	–	Van Bambeke et al. (2010)
Change the physiology of resistant cells	Dispersal of biofilms to planktonic cells	Antibiofilm exopolysaccharides	Combined with high-spectrum antibiotics	–	Rendueles et al. (2013)
		d-aminoacids	Combined with high-spectrum antibiotics (Ciprofloxacin, Tobramycin)	–	Kolodkin-Gal et al. (2010)
		Nitric Oxide (NO)	Tobramycin	–	Barraud et al. (2006)