TABLE 1.

Major human trials for testing efficacy of phage therapy and reason of failures.

Year	Brief details	Major limitations/findings	References
June 2009 to September 2011	Prospective, single center, randomized, placebo-controlled trial to study the safety and efficacy of T4-like phage cocktail in 6–24-month-old male children presenting acute diarrhoea.	• Oral coliphages showed a safe gut transit in children	Sarker et al. (2016)
		• Failed to achieve intestinal amplification attributed to too low E. coli pathogen titers not enough to support active phage infection.
		• Possible contribution of other pathogens such as Streptococcus spp. as causative agents
2014	• Study on 122 patients at the Phage Therapy Unit in Wrocław with bacterial infections to verify whether phage therapy (PT) can induce anti-phage antibodies when give through various routes (orally, locally, orally/locally, intrarectally, or orally/intrarectally).	• Phage inactivation rates (K value) showed low K values (≤1.73) seen in sera of healthy volunteers and also low K value in patients before PT (K ≤ 1.64). However, in 12.3% of examined patients (n = 15), phages given locally (n = 13) and phages given locally/orally (n = 2) showed high K values in their sera i.e., K > 18 as measured 15–60 days of PT and high phage inactivation was seen especially in patients treated with some S. aureus, P. aeruginosa, and E. faecalis phages	Łusiak-Szelachowska et al. (2014)
	• Anti-phage activity determined in sera from the 122 patients before and during PT, and in sera from 30 healthy volunteers using a neutralization test. Further, levels of anti-phage antibodies determined in sera of 19 patients PT and sera of 20 healthy volunteers using ELISA.
		• Phage inactivation by sera depends on route of administration and phage type.
2004	Double-blind, controlled clinical trial to evaluate the efficacy and safety of a therapeutic bacteriophage preparation (Biophage-PA) targeting antibiotic-resistant P. aeruginosa in chronic otitis in 24 patients	• Phage therapy showed clearing of infection but only in 3 out of 12 cases while there was only a minor reduction in bacterial counts in other participants indicating towards use of low phage dose (2 × 104 PFU) given as one reason.	Wright et al. (2009)
July 2015 to Jan 2017	Randomised, controlled, double-blind phase trial to study efficacy and tolerability of a cocktail of 12 bacteriophages (PP1131) to treat burn wounds infected by P. aeruginosa as compared to standard of care antibiotic	• Trial was halted prematurely due to poor efficacy of phage cocktail mix compared to standard of care (SOC) antibiotic.	Jault et al. (2019)
		• PP1131 titre decreased after manufacturing and participants were given a lower concentration of phages than initially expected.
		• Ancillary study showed that the bacteria isolated from patients with failed PP1131 treatment were resistant to phage doses.