Lytic bacteriophages (phages) have been known to be a potential antibacterial agent for over a century since their first formal discovery and application as a treatment against human bacterial infections in the 1920s. Though subsequent success of antibiotics had quelled investigations into phage as potential anti-infectives, increasing antibiotic resistance has hastened the reemergence of interest in phage therapy. Despite attractive advantages, including widespread prevalence, activity against multidrug-resistant (MDR) bacteria, high specificity, and activity against biofilms, phage therapy is still not considered a mainstream treatment due to several obstacles. First, the lack of reliable data regarding its safety and efficacy in clinical settings. Second, appropriate regulatory guidelines specific to phage therapeutics have not been developed. Finally, the pharmaceutical and biotech industries have not yet developed economical and scalable production processes for widespread adoption of phage therapy. While much progress has been made, many questions remain, such as the safety and toxicity of phage preparations.
Reference | Titration | Characterization | Composition & Purity | ||||
---|---|---|---|---|---|---|---|
Animal Studies | PFU | Genotype | Protein Profile | Sterility | Endotoxin | Host Cell DNA | Other Toxins |
Dufour et al., 2019 [15][67] | |||||||
Fong et al., 2019 [17][60] | |||||||
Drilling et al., 2017 [16][68] | |||||||
Drilling et al., 2014 [21][69] | |||||||
Chhibber et al., 2008 [115][70] | |||||||
Jongsoo et al., 2019 [116][71] | |||||||
Chang et al., 2018 [113][65] | |||||||
Gelman et al., 2018 [117][72] | |||||||
Cheng et al., 2017 [118][73] | |||||||
Oechslin et al., 2016 [18][74] | |||||||
Galtier et al., 2016 [81][12] | |||||||
Jun et al., 2014 [20][41] | |||||||
Takemura-Uchiyama et al. 2014 [119][75] | |||||||
Osanai, et al. 2012 [120][76] | |||||||
Pouillot, et al. 2012 [121][77] | |||||||
Ľubomíra Tóthová et al. 2011 [122][78] | |||||||
Hung, et al. 2011 [123][79] | |||||||
Hawkins, et al. 2010 [124][80] | |||||||
Sunagar, et al. 2010 [19][40] | |||||||
Nishikawa, et al. 2008 [125][81] | |||||||
Case Reports | |||||||
Lebeaux et al., 2021 [22][82] | |||||||
Ferry et al., 2020 [23][83] | |||||||
Bao et al., 2020 [24][84] | |||||||
Cano et al., 2020 [25][85] | |||||||
Rostkowska et al., 2020 [26][86] | |||||||
Doub et al., 2020 [27][87] | |||||||
Rubalskii et al., 2020 [28][88] | |||||||
Gainey et al., 2020 [29][37] | |||||||
Aslam et al., 2019 [30][38] | |||||||
Nir-Paz et al., 2019 [31][89] | |||||||
Tkhilaishvili et al., 2019 [32][90] | |||||||
Onsea et al., 2019 [33][42] | |||||||
Corbellino et al., 2019 [34][91] | |||||||
Susan et al., 2019 [35][61] | |||||||
Gilbey et al., 2019 [36][62] | |||||||
Law et al., 2019 [37][63] | |||||||
RM et al., 2019 [38][43] | |||||||
Duplessis et al., 2019 [10][92] | |||||||
Kuipers et al., 2019 [39][93] | |||||||
LaVergne et al., 2018 [44][94] | |||||||
Ferry et al., 2018 [41][58] | |||||||
Fish et al., 2018 [40][95] | |||||||
Ferry et al., 2018 [45][96] | |||||||
Hoyle et al., 2018 [42][97] | |||||||
Chan et al., 2018 [43][98] | |||||||
Ujmajuridze et al., 2018 [46][39] | |||||||
Schooley et al., 2017 [47][56] | |||||||
Zhvania et al., 2017 [48][99] | |||||||
Jennes et al., 2017 [49][100] | |||||||
Fish et al., 2016 [50][101] | |||||||
Fadlallah et al., 2015 [51][102] | |||||||
Rose et al., 2014 [52][103] | |||||||
Khawaldeh et al., 2011 [53][104] | |||||||
Kvachadze et al., 2011 [54][105] | |||||||
Letkiewicz et al., 2009 [55][106] | |||||||
Clinical Trials | |||||||
Leitner et al., 2020 [56][107] | |||||||
Grubb et al., 2020 [57][11] | |||||||
Fabijan et al., 2020 [58][108] | |||||||
Ooi et al., 2019 [59][109] | |||||||
Febvre et al., 2019 [60][13] | |||||||
Gindin et al., 2018 [61][110] | |||||||
McCallin et al., 2018 [62][57] | |||||||
Sarker et al., 2017 [63][15] | |||||||
McCallin et al., 2013 [64][14] | |||||||
Sarker et al., 2012 [65][16] | |||||||
Rhoads et al., 2009 [66][59] | |||||||
Patrick et al., 2018 [67][111] | |||||||
Sarker et al., 2016 [68][112] | |||||||
Wright et al., 2009 [69][64] |
Safety Monitoring | Safety Endpoints |
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General assessment | Vital signs; physical exam; subjective symptoms |
Labs—Chemistry | Liver function; kidney function; electrolytes; glucose; CRP |
Labs—Hematology | CBC with differential; ESR |
Pharmacology | Absorption; distribution; excretion; metabolism endpoints (e.g., LE50, ED50, TI) |
Immune Response | Non-specific and specific immune responses (e.g., DC, inflammatory factor level; phage specific antibodies) |
Phage Parameters | Phage Preparation Measurements |
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Identify | Morphology |
Potency | Titer |
Sequencing | Genotype; Protein profile |
Bacterial contaminants | Viable bacteria; Endotoxin; Enterotoxin B; Bacterial DNA |
Other impurities | CsCl |
Others | Sterile; PH; shelf time; suspended buffer; osmotic pressure |