Table 2. Synergism Strategies Involving AMPs and Antibiotics.

peptide	antibiotic	bacteria	types of activity and experimental assaysa	proposed mechanisms of action (AMP; antibiotic)	ref
FK16	vancomycin	P. aeruginosa PAO1	synergism (FICI = 0.25) in vitro tests	membrane rupture; inhibition of cell wall synthesis	(48)
		P. aeruginosa ATCC 19660	synergism (FICI = 0.37) in vitro tests
		P. aeruginosa OS	synergism (FICI = 0.37) in vitro tests
L11W	penicillin	multidrug-resistant S. epidermidis	synergism (FICI = 0.31) in vitro tests	membrane disruption; inhibition of cell wall synthesis	(49)
	ampicillin		synergism (FICI = 0.28) in vitro tests	membrane disruption; inhibition of cell wall synthesis
	erythromycin		synergism (FICI = 0.28) in vitro tests	membrane disruption; binding to 50S ribosomal subunits, blocking protein synthesis
L12W	penicillin	multidrug-resistant S. epidermidis	synergism (FICI = 0.28) in vitro tests	membrane disruption; inhibition of cell wall synthesis	(49)
	ampicillin		synergism (FICI = 0.25) in vitro tests	membrane disruption; inhibition of cell wall synthesis
	erythromycin		synergism (FICI = 0.28) in vitro tests	membrane disruption; binding to 50S ribosomal subunits, blocking protein synthesis
I1WL5W	penicillin	multidrug-resistant S. epidermidis	synergism (FICI = 0.28) in vitro tests	membrane disruption; inhibition of cell wall synthesis	(49)
	ampicillin		synergism (FICI = 0.25) in vitro tests	membrane disruption; inhibition of cell wall synthesis
	erythromycin		synergism (FICI = 0.28) in vitro tests	membrane disruption; binding to 50S ribosomal subunits, blocking protein synthesis
	tetracycline		synergism (FICI = 0.28) in vitro tests	membrane disruption; binding to 30S ribosomal subunits, blocking protein synthesis
I4WL5W	penicillin	multidrug-resistant S. epidermidis	synergism (FICI = 0.18) in vitro tests	membrane disruption; inhibition of cell wall synthesis	(49)
	ampicillin		synergism (FICI = 0.15) in vitro tests	membrane disruption; inhibition of cell wall synthesis
	erythromycin		synergism (FICI = 0.31) in vitro tests	membrane disruption; binding to 50S ribosomal subunits, blocking protein synthesis
Sphistin	rifampicin	P. aeruginosa ATCC 9027	synergism (FICI = 0.31) in vitro tests	membrane disruption; inhibition of RNA synthesis	(50)
	azithromycin		synergism (FICI = 0.31) in vitro tests	membrane disruption; inhibition of protein synthesis
Sph12–38	rifampicin	P. aeruginosa ATCC 9027	synergism (FICI = 0.37) in vitro tests; complete wound healing in vivo model between 5 and 7 days	membrane disruption; inhibition of RNA synthesis	(50)
	azithromycin		synergism (FICI = 0.22) in vitro tests; complete wound healing in vivo model between 4 and 5 days	membrane disruption; inhibition of protein synthesis
Esc(1–21)	colistin	A. baumannii (four distinct strains)	synergism (FICI = 0.25–0.37) in vitro tests	membrane perturbation in both	(36, 54)
BP203	rifampicin	colistin-resistant E. coli	synergism (FICI = 0.31–0.50) in vitro tests	b; inhibition of cell wall synthesis	(51, 55)
	meropenem	colistin-resistant K. pneumoniae	synergism (FICI = 0.25–0.50) in vitro tests	b; inhibition of cell wall synthesis
	chloramphenicol		synergism (FICI = 0.14–0.37) in vitro tests	b; inhibition of protein synthesis
	rifampicin		synergism (FICI = 0.02–0.31) in vitro tests	b; inhibition of RNA synthesis
	ciprofloxacin		synergism (FICI = 0.37) in vitro tests	b; inhibition of type II topoisomerase (DNA gyrase) and topoisomerase IV
	ceftazidime		synergism (FICI = 0.07–0.18) in vitro tests	b; inhibition of cell wall synthesis
MAP-0403 J-2	colistin	colistin-resistant E. coli	synergism (FICI = 0.31–0.50) in vitro tests	b; membrane perturbation	(51, 56)
		chloramphenicol	synergism (FICI = 0.50) in vitro tests	b; inhibition of protein synthesis
		rifampicin	synergism (FICI = 0.18–0.50) in vitro tests	b; inhibition of RNA synthesis
		ceftazidime	synergism (FICI = 0.25–0.37) in vitro tests	b; inhibition of cell wall synthesis
	chloramphenicol	colistin-resistant K. pneumoniae	synergism (FICI = 0.25–0.37) in vitro tests	b; inhibition of protein synthesis
		rifampicin	synergism (FICI = 0.07–0.37) in vitro tests	b; inhibition of RNA synthesis
		ciprofloxacin	synergism (FICI = 0.37) in vitro tests	b; inhibition of type II topoisomerase (DNA gyrase) and topoisomerase IV
		ceftazidime	synergism (FICI = 0.12–0.50) in vitro tests	b; inhibition of cell wall synthesis
A3-APO	colistin	K. pneumoniae K97/09	synergism (FICI = 0.08) in vitro tests; increased survival rate by 100% in vivo tests	disintegrates bacterial membrane and inhibits the 70 kDa heat shock protein DnaK; membrane perturbation	(47, 57)
	imipenem	A. baumannii BAA-1605	synergism (FICI = 0.08) in vitro tests	disintegrates bacterial membrane and inhibits the 70 kDa heat shock protein DnaK; inhibition of cell wall synthesis
Chex1-Arg20c	meropenem	E. coli UNT167-1	synergism (FICI = 0.38) in vitro tests	membrane rupture; inhibition of cell wall synthesis	(47, 58)
	ceftazidime	Burkholderia pseudomallei 1026b	increased survival rate by 80% in vivo tests	membrane rupture; inhibition of cell wall synthesis
Tridecaptin M	rifampicin	A. baumannii ATCC 19606	synergism (FICI = 0.31) in vitro tests	membrane permeability; inhibition of RNA synthesis	(52, 59)
	vancomycin		synergism (FICI = 0.31) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	clarithromycin		synergism (FICI = 0.31) in vitro tests	membrane permeability; binding to 50S ribosomal subunits, blocking protein synthesis
	imipenem		synergism (FICI = 0.37) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	ceftazidime		synergism (FICI = 0.28) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	ceftazidime	A. baumannii ATCC 2803	synergism (FICI = 0.31) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	rifampicin	A. baumannii AB1	synergism (FICI = 0.27) in vitro tests	membrane permeability; inhibition of RNA synthesis
	vancomycin		synergism (FICI = 0.31) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	rifampicin	A. baumannii AB2	synergism (FICI = 0.28) in vitro tests	membrane permeability; inhibition of RNA synthesis
	vancomycin		synergism (FICI = 0.31) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	rifampicin	A. baumannii GMCH05	synergism (FICI = 0.25) in vitro tests	membrane permeability; inhibition of RNA synthesis
	vancomycin		synergism (FICI = 0.28) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	ceftazidime		synergism (FICI = 0.28) in vitro tests	membrane permeability; inhibition of cell wall synthesis
	rifampicin	A. baumannii ATCC 19606	bacterial death below the detection limit in 4 h in an ex vivo blood infection model	membrane permeability; inhibition of RNA synthesis
Esc(1–21)-1c	erythromycin	P. aeruginosa PAO1	synergism (FICI = 0.37) in vitro tests	membrane perturbation; binding to 50S ribosomal subunits, blocking protein synthesis	(53, 54)
	chloramphenicol		synergism (FICI = 0.25) in vitro tests	membrane perturbation; inhibition of protein synthesis
	tetracycline		synergism (FICI = 0.37) in vitro tests	membrane perturbation; binding to 30S ribosomal subunits, blocking protein synthesis

^aFICI, Fractional Inhibitory Concentration Index.

^bNot reported.

^cARV-1502 is the commercial name.