From:  Exploiting bacteriophage as a potential new generation antibiotic alternative: hypothetical prototype and clinical progress

 History of bacteriophage therapy studies.

YearCountryPathogenDiseaseDescription
1919FranceShigellaBacterial dysenteryTreatment of children suffering from severe dysentery using previously isolated phages.
1921FranceStaphylococcusCarbunculosis and furunculosisThe injection of phages near the base of the carbuncles and furuncles in 6 patients led to a reduction in swelling, pain, and fever.
1927IndiaV. choleraeCholeraThis study was the first to use intravenous administration of bacteriophages by Asheshov in India.
1929USAStaphylococcusChronic furunculosisSubcutaneous treatment of 208 patients showed 78% with no recurrent infections.
1929USAStaphylococcusSepticemiaRemarkable success.
1931EgyptYersinia pestisBubonic plagueIn 1927, d’Herelle treated 4 cases of bubonic plague successfully by injecting bacteriophages into the buboes.
1932USAS. aureusMeningitisRemarkable success.
1936USAStaphylococcusStaphylococcal bacteraemiaRelatively successful treatment in 100 of patients.
1936FranceStaphylococcusSurgical infectionsCure of abscesses using polyvalent phages.
1936GeorgiaSalmonella typhiTyphoid feverTreatment of 21 patients resulted in a drop of 10.8% in mortality and 43.2% in complications.
1936GeorgiaSalmonella and ShigellaAcute colitisAll 43 patients with colitis were cured after treatment using “bacti-intesti-phage”.
1936GeorgiaS. typhiPeritonitis caused by intestinal perforations in typhoid feverMortality was reduced from 85% to 20–35%.
1942USAStaphylococcusStaphylococcal bacteraemiaVery positive results in the treatment of 500 patients.
1946USASalmonellaTyphoid feverThe results were inconclusive; however, the positive results were astounding and encouraged them to continue the research.
1949CanadaSalmonellaTyphoid feverSeveral phage cocktails were used to treat 100 patients. The most successful one reduced the mortality rate from 20% to 2%.
1968RussiaSalmonella and ShigellaAcute colitisAll 43 patients with colitis were cured after treatment using “bacti-intesti-phage”.
1974RussiaProteus, Staphylococcus, and StreptococcusPeritonitis, osteomyelitis, lung abscesses, and postsurgical wound infectionsSubcutaneous or through surgical wounds administration of phages in 236 patients resistant to antibiotics with a success rate of 92%.
1976RussiaAbscessing pneumoniaA complex treatment was given to the patients, including intensive antibacterial therapy, immunotherapy, bacteriophage, protein preparations, vitamin therapy, and fresh blood transfusion.
1978RussiaE. coli and ProteusAntibiotic-associated intestinal dysbiosisA combination of phages and Bifidobacteria was used to restore the intestinal microbiota in 500 infants.
1978RussiaE. coli, Proteus, Staphylococcus, and StreptococcusSuppurative surgical infectionsA comparison between commercial phage preparations and phages selected against bacterial strains isolated from patients was done. The selected phages were more effective in treating 60 patients.
1979FranceEnterobacter, Klebsiella, Proteus, Providencia, and S. aureusChronic orthopaedic infectionsSeven cases of chronic orthopaedic infections were successfully treated with phages.
1980RussiaE. coli, Proteus, Staphylococcus, and StreptococcusLung and pleural infectionsTreatment of 45 patients using the combination of phages and antibiotics.
1981RussiaE. coli and ProteusBacterial dysenteryA combination of phages and bifidobacteria was used to treat 59 immunosuppressed leukaemia patients. The treatment was reported to be more effective than antibiotics.
1981–1986PolandE. coli, Klebsiella, Pseudomonas, Salmonella, Shigella, and StaphylococcusGastrointestinal tract, skin, head, and neck infectionsPhages were administered to over 1,000 patients in a series of studies. The success rates varied between 91% and 96%.
1982RussiaStaphylococcusLung and pleural infectionsFull recovery was reported in 82% of the patients treated with phages as opposed to 64% of patients treated with antibiotics.
1984RussiaShigellaBacterial dysenteryThe double-blinded study showed a 10-fold lower incidence of dysentery in those treated with phages.
1984RussiaP. aeruginosa and S. aureus-A prophylactic mouthwash was administered to patients with acute leukemia.
1986PolandE. coli, Klebsiella, Proteus, Pseudomonas, and StaphylococcusBacterial monoinfections and polyinfectionsThe immunogenic effects of therapeutic phages were evaluated in 57 patients, showing an insignificant impact.
1986PolandStaphylococcus and several Gram-negative bacteriaSuppurative infectionsDuring therapy, phages seemed to infiltrate the blood circulation and urinary tract.
1987PolandE. coli, Klebsiella, Proteus, Pseudomonas, and StaphylococcusSuppurative skin infectionsA success rate of 74% in 31 patients with chronically infected skin ulcers was observed upon phage administration.
1988RussiaPseudomonas and StaphylococcusPost-surgical infectionsTherapeutic phages were administered to 65 of 131 cancer patients, while the others received antibiotics. Phage therapy was successful in 82% of the patients in comparison to 61% success using antibiotics.
1991RussiaEnterococcus, E. coli, P. aeruginosa, Proteus, Staphylococcus, and StreptococcusInfectious allergosisA total of 1,380 patients with infectious allergosis were treated using 3 different regimens: antibiotics, phages, and a mixture of both. The rates of success were 48%, 86%, and 83%, respectively.
1992RussiaKlebsiella ozaenae, K. pneumoniae, and K. RhinoscleromatisPurulent inflammatory diseasesThe administration of Klebsiella bacteriophages was successful in treating 109 patients with Klebsiella infections.
1993RussiaSalmonella and ShigellaBacterial dysentery and salmonellosisA total of 1,646 children were successfully treated with phages and a combination of antibiotics and phages, where antibiotics alone were ineffective.
1994PolandE. coliRecurrent subphrenic abscessA case of recurrent subphrenic abscess caused by an antibiotic-resistant strain of E. coli was successfully treated with phages.
1995RussiaE. coli, Proteus, and StaphylococcusInflammatory urogenital diseasesAdapted phages were used to treat 46 patients. The treatment was successful in 92% of the patients, while 84% showed bacterial clearance.
1999PolandK. pneumoniaeCerebrospinal meningitisOral administration of a phage preparation successfully cleared bacteria from cerebrospinal fluid in a newborn.
2001RussiaProteus, Staphylococcus, and StreptococcusBurn woundsPyophage treatment in patients with burn wounds reduced septic complications, had a 2-fold reduction of Staphylococci and Streptococci, a 1.5-fold reduction of Proteus, and a full reduction of E. coli.
2002Republic of GeorgiaE. coli, Proteus, Pseudomonas, and StaphylococcusUlcers and woundsPhageBioDerm was administered and showed a 70% rate of success.
2009UKP. aeruginosaChronic otitisBacteriophage significantly reduced the numbers of P. aeruginosa in the phage-treated group in chronic otitis externa patients.
2015FranceS. aureusEye corneal abscess and interstitial keratitisBacteriophage eye drops with successful results after 6 months.
2017NetherlandsS. aureusDermatosesSuccessful treatment of chronic S. aureus with endolysin Staphefekt phage.
2017Republic of GeorgiaStaphylococciNetherton syndromeSuccessful treatment of manifestations of Netherton syndrome.
2017BelgiumP. aeruginosaP. aeruginosa septicaemia and acute kidney injuryTreatment of colistin-only-sensitive P. aeruginosa septicaemia.

The Table is adapted with the permission of [36]. Copyright remains with the author(s) or their institution(s).