Phage therapy: An alternative to antibiotics in the age of multi-drug resistance

Table 1 Published findings on phage therapy in humans and in animal models

Causative agent	Model	Condition	Oral	Result summary1	Ref.
Shigella dysenteriae	Human	Dysentery	Oral	All four treated individuals recovered after 24 h	[1]
Vibrio cholerae	Human	Cholera	Oral	68 of 73 survived in treatment group and only 44 of 118 in control group	[1]
Pseudomonas aeruginosa	Murine	Sepsis	Oral	66.7% reduced mortality	[38]
Clostridium difficile	Hamster	Ileocecitis	Oral	Co-administration with C. difficile prevented infection	[39]
	Hamster	Ileocecitis	Oral dose every 8 h for 72 h	92% reduced mortality	[39]
Vancomycin-resistant Enterococcus faecium	Murine	Bacteremia	i.p.	100% reduced mortality	[41]
β-lactamase producing Escherichia coli	Murine	Bacteremia	i.p.	100% reduced mortality	[42]
Imipenem-resistant P. aeruginosa	Murine	Bacteremia	i.p.	100% reduced mortality	[43]
Acinetobacter baumannii, P. aeruginosa and Staphylococcus aureus	Murine	Sepsis	i.p.	Animals protected against fatal dose of A. baumannii and P. aeruginosa but not S. aureus	[44]
Escherichia coli	Murine	Meningitis and Sepsis	i.p. or s.c.	100% and 50% reduced mortality for meningitis and sepsis, respectively	[45]
MDR Vibrio parahaemolyticus	Murine	Sepsis	i.p. and oral	92% and 84% reduced mortality for i.p. and oral routes, respectively	[46]
S. aureus	Rabbit	Wound infection	s.c.	Co-administration with S. aureus prevented infection	[47]
MDR S. aureus	Human	Diabetic foot ulcer	Topical	All 6 treated patients recovered	[50]
Unclassified bacterial dysentery	Human	Dysentery	Oral	Phage cocktail improved symptoms of 74% of 219 patients	[51]
Salmonella typhi	Human	Typhoid	Oral	In cohort of 18577 children, phage treatment associated with 5-fold decrease in typhoid incidence compared to placebo	[49]
Antibiotic-resistant P. aeruginosa	Human	Chronic Otitis	Oral	Phage treatment safe and symptoms improved in double-blind, placebo-controlled Phase I/II trial	[61]

¹Reduced mortality is for phage-treated groups and are relative to 100% mortality in control animals, unless otherwise specified. MDR: Multi-drug-resistant; i.p.: Intraperitoneal injection; s.c.: Subcutaneous injection.

Table 2 Recently published findings on phage lytic enzymes

	Lytic enzyme	Model	Target pathogens	Result summary	Ref.
Phage-derived lysins	ABgp46	In vitro	MDR Acinetobacter baumannii, Pseudomonas aeruginosa, and Salmonella typhimurium	Cross-inoculation significantly reduced bacterial density	[64]
	PlyF307	Murine	MDR A. baumannii	i.p. treatment rescued mice from lethal bacteremia	[65]
	Cpl-1	Murine	Streptococcus pneumoniae	i.p. treatment rescued mice from lethal pneumonia	[66]
	Cocktail of 6 distinct lysins	In vitro and murine in vivo	MRSA	Effective against biofilms in vitro and protected mice from lethal sepsis	[67]
	PlyCD	In vitro and ex vivo	Clostridium difficile	Reduced C. difficile colonization	[68]
	PlySs2	Murine	Streptococcus pyogenes and MRSA	i.p. treatment reduced mortality from lethal bacteremia	[69]
	PlyG	In vitro	Bacillus anthracis	Eliminated B. anthracis spores and vegetative cells	[71]
Bioengineered chimeric lysins	CHAPK	In vitro	MRSA	Eliminated MRSA and dispersed biofilms	[72]
	ClyH	Murine	MRSA	Treatment rescued mice from bacteremia	[73]
	Cpl-711	Murine	S. pneumoniae	Treatment rescued mice from bacteremia	[74]
	Ply187	Murine	Staphylococcus aureus	Prevented bacterial endophthalmitis	[75]
	Artilysins	Nematode gut	P. aeruginosa	Decolonized P. aeruginosa from gut	[76]
		Human keratinocytes	A. baumannii	Protected cells from bacterial challenge	[76]
Lysin and antibiotic combination therapy	CF-301	Murine	MRSA	Lysin treatment was most effective when combined with vancomycin or daptomycin	[77]
	MR-10	Murine	Burn wound infection	Lysin treatment was most effective when combined with minocycline	[78]

MDR: Multi-drug-resistant; i.p.: Intraperitoneal injection; MRSA: Methicillin-resistant S. aureus.