Next Article in Journal
Local Antibiotic Delivery Options in Prosthetic Joint Infection
Next Article in Special Issue
The Potential of Bacteriophage-Antibiotic Combination Therapy in Treating Infections with Multidrug-Resistant Bacteria
Previous Article in Journal
Editorial for the Special Issue: “Current Technique for Antibiotic Susceptibility Test: Advantages and Limitations; Need for Next-Generation Test”
Previous Article in Special Issue
Phage Therapy vs. the Use of Antibiotics in the Treatment of Salmonella-Infected Chickens: Comparison of Effects on Hematological Parameters and Selected Biochemical Markers
 
 
Search for Articles:
Title / Keyword
Author / Affiliation / Email
Journal
Article Type
 
 
Advanced Search
 
Section
Special Issue
Volume
Issue
Number
Page
 
Journals
Antibiotics
Volume 12
Issue 4
10.3390/antibiotics12040751
antibiotics-logo
Submit to this Journal Review for this Journal Propose a Special Issue
► Article Menu

Article Menu

share Share announcement Help format_quote Cite question_answer Discuss in SciProfiles thumb_up
...
Endorse textsms
...
Comment
first_page
settings
Order Article Reprints
Font Type:
Arial Georgia Verdana
Font Size:
Aa Aa Aa
Line Spacing:
Column Width:
Background:
Review

A Century of Clinical Use of Phages: A Literature Review

by
Kevin Diallo
1,* and
Alain Dublanchet
2
1
Department of Infective and Tropical Diseases and Internal Medicine, University Hospital of la Reunion, 97448 Saint-Pierre, France
2
Independent Researcher, 2465 Rue Céline Robert, 94300 Vincennes, France
*
Author to whom correspondence should be addressed.
Antibiotics 2023, 12(4), 751; https://doi.org/10.3390/antibiotics12040751
Submission received: 25 February 2023 / Revised: 9 April 2023 / Accepted: 10 April 2023 / Published: 13 April 2023
(This article belongs to the Special Issue Antibiotics vs. Phage Therapy, 2nd Edition)
Browse Figure
Review Reports Versions Notes

Abstract

:
Growing antibiotic resistance and the broken antibiotic market have renewed interest in the use of phages, a century-old therapy that fell into oblivion in the West after two decades of promising results. This literature review with a particular focus on French literature aims to complement current scientific databases with medical and non-medical publications on the clinical use of phages. While several cases of successful treatment with phages have been reported, prospective randomized clinical trials are needed to confirm the efficacy of this therapy.

1. Introduction

Growing antibiotic resistance and the broken antibiotic market currently pose a major threat to global health. In this context, new therapeutic strategies are needed to avoid returning to the pre-antibiotic era. One potential solution is the use of phages, a century-old therapy that fell into oblivion in the West after two decades of promising results. Phages (or bacteriophages) are bacteria-specific viruses that inject their genome into bacterial cells and use the bacterial metabolism to replicate. The life cycle of phages is either lytic or lysogenic. During the lytic cycle, the injected phage genome replicates and destroys the bacterial cell, thus inhibiting bacterial growth. During the lysogenic cycle, the injected genome remains in the host’s genome, where it enters a dormant state [1,2]. Lytic phages will be the focus of this literature review, as only they have the capacity to destroy infected bacteria.
Phages are well absorbed enterally and transmucosally [3]. They have short half-lives in vivo as they are rapidly destroyed by the immune system, in particular the reticulo-endothelial system. When they infect their target bacteria, however, they can multiply exponentially [4]. Phages have been classified by the International Committee for Taxonomy of Viruses into 12 families, with Straboviridae, Autographiviridae, and Drexlerviridae accounting for over 95% of identified phages [5]. Phages present several advantages: they self-replicate; they have greater specificity than antibiotics; they can be used in patients with allergy to antibiotics; they have a low rate of side effects; their production cost is low; they can be administered through different routes; they can present synergistic effects when combined with antibiotics; they are effective against biofilm; and in the case of bacterial resistance to a specific phage, other phages can be used against the resistant bacterium [1,6]. However, phages also have disadvantages: phage treatment can be initiated only after the causative agent has been identified; multi-bacterial infections require cocktails containing several phages; phage preparations must be sterilized; phage preparations have to be very clean and endotoxin free; phage treatment can induce an immune response in humans; pharmacokinetic data on the action of phages in the human body are lacking; and phages have yet to be properly classified by regulatory agencies [1,6,7].
Many cases of successful treatment with phages have been reported over the last century. Yet, several of these reports are missing from current scientific databases: some fell into oblivion before the advent of databases, others were published in non-medical outlets, and others were written in languages other than English [8]. While many case reports of treatment with phages have an insufficient level of proof, a century of experimentation cannot be ignored.
This literature review with a particular focus on French literature aims to complement current scientific databases with medical and non-medical publications on the clinical use of phages in humans.

2. Context

2.1. History of Phage Therapy

Phages were first described as ultra-microscopic viruses by Frederick Twort in 1915 and characterized as bacteriophages by Félix d’Hérelle two years later [9,10]. They were introduced in the former Eastern Bloc by a student of d’Hérelle, George Eliava, who founded a research institute specifically dedicated to phage therapy in Tbilissi, Georgia, in 1923.
In the 1920s and 1930s, phages were used worldwide for several indications in humans. Several large pharmaceutical companies produced commercial phage preparations at the time: Eli Lilly (Indianapolis, IN, USA) in the early 1930s, Abbott Labs (Chicago, IL, USA) in the early 1930s, and Bristol-Myers Squibb (New York, NY, USA) from the early 1930s to the 1940s [11]. However, phage therapy failed to impose itself in the West due to inconsistent treatment results, a poor understanding of phages’ mechanism of action, and the advent of broad-spectrum antibiotics [1]. The therapy was discredited in two reports published in 1934 and 1941 by Eaton and Krueger [12,13,14,15,16]. While some Western companies continued to produce phages afterwards (in particular for the food processing industry), the use of phages in humans was largely abandoned.
In the former Eastern Bloc, the institute founded by Eliava in Georgia continued to carry out major research on phage therapy and supplied phage products to the USSR throughout the 20th century. Renamed the G. Eliava Institute of Bacteriophages, Microbiology, and Virology in 1988, it pursued its research activities after the fall of the Iron Curtain. In Russia, phages are now produced commercially by the company Microgen.
In 2005, a Phage Therapy Unit was created at the Hirszfeld Institute of Immunology and Experimental Therapy in Wrocław, Poland. This unit is now the second largest center for phage research in Europe after the G. Eliava Institute.
Since the mid-2000s, growing antibiotic resistance has prompted institutes and pharmaceutical laboratories all over the world to create their own phage banks on the model of the G. Eliava Institute [17]. These include: Adaptive Phage Therapeutics in the United States, Biobank, First Affiliated Hospital of Xi’an Jiaotong University, Institute for Protein Science and Phage Research in China, the Bacteriophage Bank of Korea [18], the Israeli Phage Bank at the Hebrew University of Jerusalem in Israel [19], the National Collection of Type Cultures, the Bacteriophage Collection in the United Kingdom, Fagenbank in the Netherlands, DMZ in Germany, Queen Astrid Military Hospital in Belgium, and Pherecydes Pharma in France.
Despite this renewed interest in phage therapy, the efficacy of phages has yet to be demonstrated.

2.2. Legal Framework for the Use of Phage Therapy in Humans

Phages are classified as drugs in the US and as medicinal products in the EU [20]. Like other drugs, they are subject to marketing and manufacturing authorization from the Food and Drug Administration (FDA) in the US and the European Medicines Agency (EMA) in the EU.
To obtain marketing authorization, phage therapies must first be validated in preclinical in vitro and in vivo studies. Once these are completed, phase I to IV clinical trials are required to confirm their safety and efficacy in humans. To date, no phage therapy has reached phase IV of clinical trials.
To receive manufacturing authorization, phage products must comply with good manufacturing practice (GMP) standards, which involve a high level of purification and sterilization. However, given the lack of fit between these standards and the viral nature of phages, no phage product has so far been approved for use in humans by the EMA or the FDA. Phage production is authorized only for compassionate use and clinical research under Article 37 of the Declaration of Helsinki.
Marketing regulations and GMP standards are barriers limiting pharmaceutical investment in phage therapy [20].

2.3. Safety of Phage Therapy in Humans

The human body is routinely exposed to large numbers of endogenous phages. Since phages are composed only of proteins and DNA and do not release toxins when they die, their toxicity is low in humans. Phages must nevertheless be purified to reduce their virulence and ensure their safe administration [3].
Bacteria destroyed by phages can release bacterial toxins, and excessive bacterial lysis often causes immune system reactions. These phenomena, however, occur mainly when phages are administered intravenously. Other routes of administration can be used safely.
In 2009, Merabishvili et al. proposed a quality control for the safe use of purified phage cocktails against Staphylococcus aureus and Pseudomonas aeruginosa [21]. In 2014, an international panel composed of 29 experts from ten countries developed quality, safety, and efficacy requirements for sustainable phage therapy products [22]. Such requirements could replace current GMP standards, which would facilitate the use of phage therapy in humans.

2.4. Use of Phages in Food Processing and Plant Disease Control

Several studies have shown the efficacy and safety of using phage products in food processing and plant disease control [23,24,25,26].
Intralytix (Columbia, MA, USA) markets three phage products for food processing: ListShield™ against Listeria monocytogenes, EcoShield™ against Escherichia coli, and SalmoFresh™ against Salmonella spp. Omnilytics (Sandy, UT, USA) sells several phage products, including Agriphage™, for use in agriculture. Elanco (Greenfield, IN, USA) markets Finalyse™, an anti-bacterial spray targeting E. coli O157. In Europe, Micreos (Wageningen, The Netherlands) produces Listex™ and Salmonelex™, both of which were approved by the FDA. APS Biocontrol (Dundee, SC, UK) produces Biolyse®, a phage product sprayed on potatoes during processing. All these products have been approved by the FDA and/or the EMA [6].

3. Literature Review of a Century of Clinical Use of Phages

A search of the MEDLINE database was performed without language restrictions to identify articles on phage therapy published between 1922 and 2022. The following keywords were used: (phage OR phage therapy OR bacteriophage) AND (treatment OR use OR therapy) AND (clinical OR human). The titles and abstracts of identified articles were screened for inclusion. Prospective randomized clinical trials, literature reviews, prospective non-randomized clinical trials, and isolated case reports evaluating the clinical use of phages were included in the review. We excluded articles that did not deal with the use of phages in humans and those referring to articles already cited that did not bring new cases to our analysis.
The reference lists of selected articles were perused to identify other relevant publications on phage therapy. These publications consisted of books, theses, and medical and non-medical articles published between 1915 and 2022. Publications in languages other than English were considered, with a particular focus on French literature. All identified publications describing cases of phage therapy were included in the review.
The main prospective randomized clinical trials, literature reviews, and prospective non-randomized clinical trials are presented in Table 1.
Isolated case reports published after 1945 are shown in Table 2, while those published prior to 1945 appear in Table 3. We took 1945 as a cut-off year as this corresponds to the period when broad-spectrum antibiotic therapy was introduced and phage therapy lost credibility in the West. Moreover, phages were mostly used in isolation before 1945 and were generally combined with antibiotics after that date.
Studies were considered to have demonstrated the efficacy of phage treatment if 50% of evaluated patients had a favorable outcome. Studies that did not specify the number of improvements or cures were classified as unspecified. Figure 1 shows the distribution of articles on phage therapy for the main clinical foci of infection.

3.1. Prospective Randomized Clinical Trials

Our search of the MEDLINE database identified nine prospective randomized trials evaluating phage therapy.
In 2021, Leitner et al. performed a randomized placebo-controlled clinical trial at the Alexander Tsulukidze National Centre of Urology in Tbilisi, Georgia, to assess the efficacy of Pyophage in 97 men with urinary tract infection [30]. Between 2017 and 2018, 28 men received Pyophage, 32 a placebo, and 37 an antibiotic treatment. No difference in treatment success rates was observed between the three groups.
In 2019, Febvre et al. and Gingin et al. presented the results of the Bacteriophage for Gastrointestinal Health (PHAGE) study, which aimed to determine the safety and tolerability of phages in healthy adults with mild to moderate gastrointestinal distress [39,40]. The PHAGE study was a randomized, double-blind, placebo-controlled crossover intervention, in which 32 patients received a treatment containing four strains of phages (LH01-Myoviridae, LL5-Siphoviridae, T4D-Myoviridae and LL12-Myoviridae) and a placebo, each for a period of 28 days. Febvre et al. reported that phage consumption caused minimal disruption to the gut microbiota. Gindin et al. found no effect of treatment sequence on comprehensive metabolic panel outcomes.
In 2019, Ooi et al. published the results of a phase I clinical trial assessing the safety, tolerability, and preliminary efficacy of intranasal doses of experimental phage cocktail AB-SA01 in patients with recalcitrant chronic rhinosinusitis who had positive S. aureus cultures sensitive to AB-SA01 [46]. Three cohorts of three patients each received successive intranasal doses of AB-SA01 twice daily at a concentration of 3 × 10⁸ PFU for seven days (cohort 1), 3 × 108 PFU for 14 days (cohort 2), and 3 × 109 PFU for 14 days (cohort 3). Treatment was well tolerated overall, and no serious adverse events or deaths were reported. Preliminary efficacy results showed favorable outcomes, with clinical and microbiological evidence of infection eradication in two of the nine evaluated patients.
The results of the “PhagoBurn” phase I/II randomized clinical trial were published in 2018 by Jault et al. [52]. The aim of this trial was to compare the efficacy and tolerability of a cocktail of anti-P. aeruginosa phages to standard of care (silver sulfadiazine) in the treatment of burn wound infections. Twenty-seven patients were randomly allocated to receive a topical application of either treatment daily for 7 days, with 14 days of follow-up. Safety was evaluated in all patients who received at least one phage dressing (treatment group) or one silver sulfadiazine dressing (control group). However, in this study, the applied phage titer was extremely low, which contributed to clinical failure. The trial was stopped before termination due to insufficient efficacy of their phage cocktail.
The 2016 trial by Sarker et al., supported by a grant from Nestlé Nutrition and Nestlé Health Science, assessed the safety and efficacy of a T4-like phage cocktail compared to the Microgen ColiProteus phage cocktail and a placebo in Bangladeshi children hospitalized with acute bacterial infection or diarrhea [52]. No adverse event attributable to the oral application of phages was reported. Treated children had higher fecal phage prevalence and titers than those who received a placebo. However, the oral phages failed to achieve intestinal replication and to improve diarrhea outcome, possibly because phage coverage was insufficient and E. coli pathogen titers were too low.
In 2009, Rhoads et al. conducted a phase I trial to evaluate the safety of a phage cocktail for the treatment of venous leg ulcers in humans [59]. Forty-two patients with chronic venous leg ulcers were included, 39 of whom completed the trial. The ulcers were treated with either a saline control or a phage preparation targeting P. aeruginosa, S. aureus, and E. coli for a period of 12 weeks. Follow-up continued through week 24. No adverse events attributable to the phage cocktail were observed. No significant difference was found between the test and control groups in terms of frequency of adverse events, rate of cure or frequency of cure.
In 2009, Wright et al. published the results of a phase I/II trial assessing the safety and efficacy of the phage preparation Biophage-PA in patients with chronic otitis caused by an antibiotic-resistant strain of P. aeruginosa [60]. A total of 24 patients randomized into two groups of 12 were treated with a single dose of Biophage-PA or a placebo and were followed up 7, 21, and 42 days after local application by the same otologist. The main outcomes were the symptoms observed by physicians (erythema, inflammation, ulceration, granulation, polyps, amount of discharge, type of discharge, and odor) and those reported by patients (discomfort, itchiness, wetness, and smell). No adverse events were observed. In the phage-treated group, pooled clinical indicators significantly improved, and P. aeruginosa counts significantly decreased from baseline, demonstrating the efficacy of the phage preparation.
In 2005, Bruttin et al. evaluated the safety of E. coli phage T4 in 15 healthy adult volunteers [62]. All patients included in this crossover study received a low dose of phage T4 (103 plaque-forming units (PFU)/mL), a high dose of phage (10⁵ PFU/mL), and a placebo in their drinking water. No adverse event related to the application of phage T4 was reported. Phage T4 was detected in a dose-dependent manner in the feces of patients orally exposed to phages. However, oral phage application did not result in a decrease in total fecal E. coli counts. Moreover, no substantial replication of phage T4 was observed in the commensal population of E. coli.
Three of the four trials evaluating the clinical efficacy of phages showed negative results. As the other trials were designed to evaluate the safety, tolerability and/or preliminary efficacy of phage therapy, one cannot conclude on the clinical efficacy of phages based on their results.

3.2. Literature Reviews

Twenty-one literature reviews evaluating the efficacy of phage therapy were identified. The following nine reviews covered the largest number of patients.
The 2021 literature review by Genevière et al. included 20 case reports of 51 patients treated with phages for bone and joint infections [28]. The overall success rate was 71%.
In 2020, Clarke et al. published a literature review of 17 case reports assessing the safety and efficacy of phage therapy in 277 patients with bone and joint infections [33]. Clinical resolution was observed in 93.1% of cases.
The efficacy of phage therapy was evaluated in two meta-analyses: one by Abedon et al. (2011) and the other by Kutter et al. (2014) [53,57]. Both meta-analyses included studies carried out in the former Eastern Bloc. The disparity in methods used and the wide variety of treated infections make it difficult to conclude on the efficacy of evaluated treatments.
In their 2012 literature review, Miecdzybrodzki et al. retrospectively evaluated 153 patients treated with phages at the Hirszfeld Institute of Immunology and Experimental Therapy in Poland between January 2008 and December 2010 [56]. They found phages to be well tolerated and to have overall efficacy.
In 2009, Chanishvili et al. reported several cases of patients treated with phages at the G. Eliava Institute in Georgia [58]. One cannot not conclude on the efficacy of phages due to the disparity in methods used and the range of treated infections.
In their 2000 literature review, Weber-Dabrowska et al. from the Hirszfeld Institute of Immunology and Experimental Therapy in Poland reported 1307 cases of treatment with phages in patients with suppurative bacterial infections caused by different species of multidrug-resistant bacteria [64]. Their conclusions indicated a very high efficacy of phage therapy: complete cure was observed in 85.9% of cases, partial cure in 10.9% of cases, and failure in 3.8% of cases.
Two theses were identified that reviewed cases of patients treated with phages. The thesis by Domrault, published in 1998, reported 557 cases of treatment with phages in patients infected with resistant P. aeruginosa. Treatment was successful in the majority of cases [65]. In his 1931 thesis, the oldest to evaluate phage therapy, Pesce reviewed 622 cases of phage treatment and described his own use of phages in 14 patients with cutaneous infections. Here again, results were mainly positive [67].
The majority of reviews showed positive results. Seven reviews were not referenced in the MEDLINE database. Of these, two were found in articles (one in French and one in English), three in theses (all in French), and two in books (both in English). Thus, our literature review adds more than 1000 patients to the existing data.

3.3. Prospective Non-Randomized Clinical Trials

Three prospective non-randomized clinical trials were identified.
The 2021 prospective study by Patel et al. evaluated the efficacy of phage therapy in 48 patients presenting with a wound that had failed to heal after 6 weeks of conventional therapy [32]. The patients received either a phage for single bacterial infection or a cocktail of phages specific to two or more infecting bacteria. Phage treatment was applied on the wound surface five to seven times over a period of 9 months, and patients were followed for 3 months. A cure rate of 81.2% was obtained.
In 2019, Gupta et al. conducted a prospective study in 20 Indian patients treated with phages for chronic nonhealing wounds infected with E. coli, S. aureus, and P. aeruginosa [41]. A cocktail of customized phages was applied over the wounds in three to five doses. A significant improvement in wound healing was observed, with seven patients cured at Day 21.
In their 1987 prospective study, Cislo et al. evaluated the effectiveness of phage therapy in 31 patients with chronic suppurative skin infections caused by Pseudomonas spp., Staphylococcus spp., Klebsiella spp., Proteus spp., and Escherichia spp. [66]. The outcome was favorable in 23 patients.

3.4. Isolated Case Reports

Our search of the literature identified 95 case reports published since 1945. These reports concerned more than 2500 patients, and the majority showed positive results (87/95). Phage therapy was associated with antibiotic therapy in 71 of the reports. A total of 12 case reports were not referenced in the MEDLINE database. Of these, eight were found in articles (four in French and four in English), and four in theses (all in French). These case reports add 200 patients to the existing data (Table 2). The main indications and the success rate associated were osteoarticular (94%, 16/17), pulmonary (86%, 12/14), skin (91%, 10/11), and digestive (77%, 7/9) infections.
A total of 119 case reports published before 1945 were identified. The majority showed positive results (101/118). These reports concerned nearly 4000 patients. A total of 102 case reports were not referenced in the MEDLINE database. Of the identified case reports, 78 were found in articles (45 in French and 33 in English), and 23 in theses (all in French). More than 2600 patients are thus added to the existing data (Table 3). The main indications and the success rate associated were bacteremia (79%, 15/19), skin (92%, 24/26), and digestive (86%, 12/14) infections.

3.5. Research Prospects

In 2017, Leitner et al. proposed a methodology for randomized controlled trials evaluating the use of phages in the treatment of urinary tract infections [282].
A 2020 literature review by Melo et al. reported the results of preclinical studies on phage treatments conducted in Western countries over the previous ten years [283]. Some of these results are encouraging and suggest the need to conduct randomized clinical trials to confirm the efficacy of phage treatments.

4. Conclusions

This literature review identified multiple cases of successful treatment with phages in patients infected with different types of microorganisms. A total of 120 publications dealing with approximately 4000 patients were added to the existing data. However, the significant publication bias and the non-standardization of methods for the assessment of phage therapy do not allow us to conclude on the efficacy of phages. Relevant pharmacological data, including treatment dosage and duration, should be collected to help standardize evaluation methods. As we have shown previously, the literature also seems to show good results from the combination of phages and antibiotics, by a synergistic effect [284]. Prospective randomized clinical trials could then be conducted to confirm or disprove the clinical efficacy of different phage treatments. Lastly, literature reviews should be performed in different countries to identify non-referenced and/or non-translated publications on phage therapy.

Author Contributions

Conceptualization, K.D. and A.D.; methodology, K.D. and A.D.; writing—review and editing, K.D. and A.D. All authors have read and agreed to the published version of the manuscript.

Funding

This research received no external funding.

Institutional Review Board Statement

Not applicable.

Informed Consent Statement

Not applicable.

Data Availability Statement

Not applicable.

Acknowledgments

The authors would like to thank Arianne Dorval for her editorial assistance.

Conflicts of Interest

The authors declare no conflict of interest.

References

  1. Veiga-Crespo, P.; Villa, T.G. Advantages and disadvantages in the use of antibiotics or phages as therapeutic agents. In Enzybiotics: Antibiotic Enzymes as Drugs and Therapeutics; Villa, T.G., Veiga-Crespo, P., Eds.; John Wiley & Sons, Inc.: Hoboken, NJ, USA, 2009; pp. 27–48. [Google Scholar] [CrossRef]
  2. Clokie, M.R.; Millard, A.D.; Letarov, A.V.; Heaphy, S. Phages in Nature. Bacteriophage 2011, 1, 31–45. [Google Scholar] [CrossRef] [Green Version]
  3. Abedon, S.T.; Thomas-Abedon, C. Phage Therapy Pharmacology. Curr. Pharm. Biotechnol. 2010, 11, 28–47. [Google Scholar] [CrossRef] [PubMed]
  4. Pirnay, J.P.; Merabishvili, M.; Van Raemdonck, H.; De Vos, D.; Gilbert Verbeken, G. Bacteriophage production in compliance with regulatory requirements. In Bacteriophage Therapy: From Lab to Clinical Practice; Methods in Molecular Biology 1693; Azeredo, J., Sillankorva, S., Eds.; Humana Press: New York, NY, USA, 2018; pp. 233–252. [Google Scholar] [CrossRef]
  5. ICTV Report Chapters. Available online: https://ictv.global/report (accessed on 4 April 2023).
  6. Clark, J.R. Bacteriophage therapy: History and future prospects. Future Virol. 2015, 10, 449–461. [Google Scholar] [CrossRef]
  7. Hermoso, J.A.; Garcia, J.L.; Garcia, P. Taking aim on bacterial pathogens: From phage therapy to enzybiotics. Curr. Opin. Microbiol. 2007, 10, 461–472. [Google Scholar] [CrossRef] [PubMed]
  8. Anonymous. Raiders of the lost articles. Nat. Rev. Microbiol. 2010, 8, 610. [Google Scholar] [CrossRef]
  9. Twort, F.W. An investigation on the nature of the ultra-microscopic viruses. Lancet 1915, 2, 1241–1243. [Google Scholar] [CrossRef] [Green Version]
  10. d’Hérelle, F. Sur un microbe invisible antagoniste des bacilles dysentériques. C. R. Acad. Sci. Paris 1917, 165, 373–375. [Google Scholar]
  11. Straub, M.E.; Appelbaum, M. Studies on commercial bacteriophage products. JAMA 1933, 100, 110–113. [Google Scholar] [CrossRef]
  12. Eaton, M.D.; Bayne-Jones, S. Bacteriophage therapy I. Review of the principles and results of the use of bacteriophage in the treatment of infections. JAMA 1934, 103, 1769–1781. [Google Scholar] [CrossRef]
  13. Eaton, M.D.; Bayne-Jones, S. Bacteriophage therapy II. Review of the principles and results of the use of bacteriophage in the treatment of infections. JAMA 1934, 103, 1847–1853. [Google Scholar] [CrossRef]
  14. Eaton, M.D.; Bayne-Jones, S. Bacteriophage therapy III. Review of the principles and results of the use of bacteriophage in the treatment of infections. JAMA 1934, 103, 1934–1939. [Google Scholar] [CrossRef]
  15. Krueger, A.P.; Scribner, E.J. The bacteriophage: I. The bacteriophage, its nature and its therapeutic use. JAMA 1941, 116, 2160–2167. [Google Scholar] [CrossRef]
  16. Krueger, A.P.; Scribner, E.J. The bacteriophage: II. The bacteriophage, its nature and its therapeutic use. JAMA 1941, 116, 2269–2277. [Google Scholar] [CrossRef]
  17. Zaczek, M.; Weber-Dabrowska, B.; Miedzybrodzki, R.; Łusiak-Szelachowska, M.; Górski, A. Phage therapy in Poland-a centennial journey to the first ethically approved treatment facility in Europe. Front. Microbiol. 2020, 11, 1056. [Google Scholar] [CrossRef] [PubMed]
  18. Kyoungeun, C.; Heejoon, M. The Bacteriophage Bank of Korea. J. Target. Infect. Dis. 2016. [Google Scholar]
  19. Yerushalmy, O.; Khalifa, L.; Gold, N.; Rakov, C.; Alkalay-Oren, S.; Adler, K.; Ben-Porat, S.; Kraitman, R.; Gronovich, N.; Shulamit Ginat, K.; et al. The Israeli Phage Bank (IPB). Antibiotics 2020, 9, 269. [Google Scholar] [CrossRef]
  20. Fauconnier, A. Guidelines for bacteriophage product certification. In Bacteriophage Therapy Methods in Molecular Biology; Azeredo, J., Sillankorva, S., Eds.; Methods in Molecular Biology 1693; Humana Press: New York, NY, USA, 2018; pp. 253–268. [Google Scholar] [CrossRef]
  21. Merabishvili, M.; Pirnay, J.P.; Verbeken, G.; Chanishvili, N.; Tediashvili, M.; Lashkhi, N.; Glonti, T.; Krylov, V.; Mast, J.; Van Parys, L.; et al. Quality-controlled small-scale production of a well-defined bacteriophage cocktail for use in human clinical trials. PLoS ONE 2009, 4, e4944. [Google Scholar] [CrossRef]
  22. Pirnay, J.P.; Blasdel, B.G.; Bretaudeau, L.; Buckling, A.; Chanishvili, N.; Clark, J.; Corte-Real, S.; Debarbieux, L.; Dublanchet, A.; De Vos, D.; et al. Quality and safety requirements for sustainable phage therapy products. Pharm. Res. 2015, 32, 2173–2179. [Google Scholar] [CrossRef] [Green Version]
  23. Goodridge, L.D.; Bisha, B. Phage-based biocontrol strategies to reduce foodborne pathogens in foods. Bacteriophage 2011, 1, 130–137. [Google Scholar] [CrossRef] [Green Version]
  24. Sillankorva, S.M.; Oliveira, H.; Azeredo, J. Bacteriophages and their role in food safety. Int. J. Microbiol. 2012, 2012, 863945. [Google Scholar] [CrossRef] [Green Version]
  25. Endersen, L.; O’Mahony, J.; Hll, C.; Ross, P.; McAuliffe, O.; Coffey, A.A. Phage Therapy in the Food Industry. Annu. Rev. Food Sci. Technol. 2014, 5, 327–349. [Google Scholar] [CrossRef] [PubMed]
  26. Jones, J.B.; Vallad, G.E.; Iriarte, F.B.; Obradović, A.; Wernsing, M.; Jackson, L.; Balogh, B.; Momol, T.; Hong, J.C. Considerations for using bacteriophages for plant disease control. Bacteriophage 2012, 2, 208–214. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  27. Suh, G.A.; Lodise, T.P.; Tamma, P.D.; Knisely, J.M.; Alexander, J.; Aslam, S.; Barton, K.D.; Bizzell, E.; Totten, K.M.C.; Campbell, J.L.; et al. Considerations for the Use of Phage Therapy in Clinical Practice. Antimicrob. Agents Chemother. 2022, 66, e0207121. [Google Scholar] [CrossRef] [PubMed]
  28. Genevière, J.; McCallin, S.; Huttner, A.; Pham, T.T.; Suva, D. A systematic review of phage therapy applied to bone and joint infections: An analysis of success rates, treatment modalities and safety. EFORT Open. Rev. 2021, 6, 1148. [Google Scholar] [CrossRef] [PubMed]
  29. Gibb, B.P.; Hadjiargyrou, M. Bacteriophage therapy for bone and joint infections. Bone Jt. J. 2021, 103, 234–244. [Google Scholar] [CrossRef]
  30. Leitner, L.; Ujmajuridze, A.; Chanishvili, N.; Goderdzishvili, M.; Chkonia, I.; Rigvava, S.; Chkhotua, A.; Changashvili, G.; McCallin, S.; Schneider, M.P.; et al. Intravesical bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: A randomised, placebo-controlled, double-blind clinical trial. Lancet Infect. Dis. 2021, 21, 427–436. [Google Scholar] [CrossRef]
  31. Liu, D.; Van Belleghem, J.D.; de Vries, C.R.; Burgener, E.; Chen, Q.; Manasherob, R.; Aronson, J.; Amanatullah, D.; Tamma, P.; Suh, G. The Safety and Toxicity of Phage Therapy: A Review of Animal and Clinical Studies. Viruses 2021, 13, 1268. [Google Scholar] [CrossRef]
  32. Patel, D.R.; Bhartiya, S.K.; Kumar, R.; Shukla, V.; Nath, G. Use of customized bacteriophages in the treatment of chronic nonhealing wounds: A prospective study. Int. J. Low. Extrem. Wounds 2021, 20, 37–46. [Google Scholar] [CrossRef]
  33. Clarke, A.L.; De Soir, S.; Jones, J.D. The safety and efficacy of phage therapy for bone and joint infections: A systematic review. Antibiotics 2020, 9, 795. [Google Scholar] [CrossRef]
  34. Duplessis, C.A.; Biswas, B. A Review of Topical Phage Therapy for Chronically Infected Wounds and Preparations for a Randomized Adaptive Clinical Trial Evaluating Topical Phage Therapy in Chronically Infected Diabetic Foot Ulcers. Antibiotics 2020, 9, 377. [Google Scholar] [CrossRef]
  35. Fabijan, A.P.; Team, W.B.T.; Lin, R.C.Y.; Ben Zakour, N.; Iredell, J.; Maddocks, S.; Westmead Bacteriophage Therapy Team. Safety of bacteriophage therapy in severe Staphylococcus aureus infection. Nat. Microbiol. 2020, 5, 465–472. [Google Scholar] [CrossRef] [PubMed]
  36. Grubb, D.S.; Wrigley, S.D.; Freedman, K.E.; Wei, Y.; Vazquez, A.R.; Trotter, R.E.; Wallace, T.C.; Johnson, S.A.; Weir, T.L. PHAGE-2 Study: Supplemental Bacteriophages Extend Bifidobacterium animalis subsp. lactis BL04 Benefits on Gut Health and Microbiota in Healthy Adults. Nutrients 2020, 12, 2474. [Google Scholar] [CrossRef] [PubMed]
  37. Steele, A.; Stacey, H.J.; de Soir, S.; Jones, J. The safety and efficacy of phage therapy for superficial bacterial infections: A systematic review. Antibiotics 2020, 9, 754. [Google Scholar] [CrossRef] [PubMed]
  38. Desgranges, F.; Bochud, P.Y.; Resch, G. Infectiologie sur mesure-2. Phagothérapie: De la théorie à l’évidence clinique. Rev. Méd. Suisse 2019, 15, 771–775. [Google Scholar] [CrossRef] [PubMed]
  39. Febvre, H.P.; Rao, S.; Gindin, M.; Goodwin, N.D.M.; Finer, E.; Vivanco, J.S.; Lu, S.; Manter, D.K.; Wallace, T.C.; Weir, T.L. Phage Study: Effects of Supplemental Bacteriophage Intake on Inflammation and Gut Microbiota in Healthy Adults. Nutrients 2019, 11, 666. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  40. Gindin, M.; Febvre, H.P.; Rao, S.; Wallace, T.C.; Weir, T.L. Bacteriophage for Gastrointestinal Health (PHAGE) Study: Evaluating the Safety and Tolerability of Supplemental Bacteriophage Consumption. J. Am. Coll. Nutr. 2019, 38, 68–75. [Google Scholar] [CrossRef]
  41. Gupta, P.; Singh, H.S.; Shukla, V.K.; Nath, G.; Kumar Bhartiya, S. Bacteriophage therapy of chronic nonhealing wound: Clinical study. Int. J. Low. Extrem. Wounds 2019, 18, 171–175. [Google Scholar] [CrossRef]
  42. Jault, P.; Leclerc, T.; Jennes, S.; Pirnay, J.P.; Que, Y.A.; Resch, G.; Rousseau, A.F.; Ravat, F.; Carsin, H.; Le Floch, R.; et al. Efficacy and tolerability of a cocktail of bacteriophages to treat burn wounds infected by Pseudomonas aeruginosa (PhagoBurn): A randomised, controlled, double-blind phase 1/2 trial. Lancet Infect. Dis. 2019, 19, 35–45. [Google Scholar] [CrossRef]
  43. Kolenda, C. Phagothérapie et Infections Ostéo-Articulaires: Évaluation de L’activité Antibiofilm et Antibactérienne Intracellulaire D’un Assemblage de Trois Bactériophages Anti-Staphylococcus aureus. Ph.D. Thesis, Faculte de Pharmacie de Lyon, Institut des Sciences Pharmaceutiques et Biologiques, Lyon, Paris, 2019. [Google Scholar]
  44. Kortright, K.E.; Chan, B.K.; Koff, J.L.; Turner, P. Phage therapy: A renewed approach to combat antibiotic-resistant bacteria. Cell Host Microbe 2019, 25, 219–232. [Google Scholar] [CrossRef] [Green Version]
  45. McCallin, S.; Sacher, J.C.; Zheng, J.; Chan, B. Current State of Compassionate Phage Therapy. Viruses 2019, 11, 343. [Google Scholar] [CrossRef] [Green Version]
  46. Ooi, M.L.; Drilling, A.J.; Morales, S.; Fong, S.; Moraitis, S.; Macias-Valle, L.; Vreugde, S.; Psaltis, A.J.; Wormald, P.J. Safety and tolerability of bacteriophage therapy for chronic rhinosinusitis due to Staphylococcus aureus. JAMA Otolaryngol. Head Neck Surg. 2019, 145, 723–729. [Google Scholar] [CrossRef]
  47. Petrovic Fabijan, A.; Khalid, A.; Maddocks, S.; Ho, J.; Gilbey, T.; Sandaradura, I.; Lin, R.; Ben Zakour, N.; Venturini, C.; Bowring, B.; et al. Phage therapy for severe bacterial infections: A narrative review. Med. J. Aust. 2020, 212, 279–285. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  48. El Haddad, L.; Harb, C.P.; Gebara, M.A.; Stibich, M.; Chemaly, R. A systematic and critical review of bacteriophage therapy against multi-drug resistant ESKAPE organisms in humans. Clin. Infect. Dis. 2018, 69, 167–178. [Google Scholar] [CrossRef] [PubMed]
  49. McCallin, S.; Sarker, S.A.; Sultana, S.; Oechslin, F.; Brüssow, H. Metagenome analysis of Russian and Georgian Pyophage cocktails and a placebo-controlled safety trial of single phage versus phage cocktail in healthy Staphylococcus aureus carriers. Environ. Microbiol. 2018, 20, 3278–3293. [Google Scholar] [CrossRef]
  50. Morozova, V.V.; Vlassov, V.V.; Tikunova, N.V. Applications of bacteriophages in the treatment of localized infections in humans. Front. Microbiol. 2018, 9, 1696. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  51. Speck, P.; Smithyman, A. Safety and efficacy of phage therapy via the intravenous route. FEMS Microbiol. Lett. 2016, 363, fnv242. [Google Scholar] [CrossRef] [PubMed]
  52. Sarker, S.A.; Sultana, S.; Reuteler, G.; Moine, D.; Descombes, P.; Charton, F.; Bourdin, G.; McCallin, S.; Ngom-Bru, C.; Neville, T.; et al. Oral phage therapy of acute bacterial diarrhea with two coliphage preparations: A randomized trial in children from Bangladesh. eBioMedicine 2016, 4, 124–137. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  53. Kutter, E.; Borysowski, J.; Miedzybrodzki, R.; Górski, A.; Weber-Dąbrowska, B.; Kutateladze, M.; Alavidze, Z.; Goderdzishvili, M.; Adamia, R. Clinical Phage Therapy. In Phage Therapy: Current Research and Applications; Borysowski, J., Miedzybrodzki, R., Gorski, A., Eds.; Nova Science Publishers: Norfolk, UK, 2014; pp. 257–288. [Google Scholar]
  54. Soothill, J. Use of bacteriophages in the treatment of Pseudomonas aeruginosa infections. Expert Rev. Anti-Infect. Ther. 2013, 11, 909–915. [Google Scholar] [CrossRef] [PubMed]
  55. Loc-Carrillo, C.; Wu, S.; Beck, J.P. Phage therapy of wounds and related purulent infections. Bacteriophages Health Dis. 2012, 24, 185–202. [Google Scholar]
  56. Miedzybrodzki, R.; Borysowski, J.; Weber-Dabrowska, B.; Fortuna, W.; Letkiewicz, S.; Szufnarowski, K.; Pawełczyk, Z.; Rogoz, P.; Kłak, M.; Wojtasik, E.; et al. Clinical aspects of phage therapy. Adv. Virus Res. 2012, 83, 73–121. [Google Scholar] [CrossRef]
  57. Abedon, S.T.; Kuhl, S.J.; Blasdel, B.G.; Kutter, E. Phage treatment of human infections. Bacteriophage 2011, 1, 66–85. [Google Scholar] [CrossRef] [Green Version]
  58. Chanishvili, N. A Literature Review of the Practical Application of Bacteriophage Research. Georgia, T., Ed.; Richard Sharp HPA: Salisbury, UK, 2009; 184p. [Google Scholar]
  59. Rhoads, D.D.; Wolcott, R.D.; Kuskowski, M.A.; Wolcott, B.M.; Ward, L.S.; Sulakvelidze, A. Bacteriophage therapy of venous leg ulcers in humans: Results of a phase I safety trial. J. Wound Care 2009, 18, 237–243. [Google Scholar] [CrossRef] [PubMed]
  60. Wright, A.; Hawkins, C.H.; Anggard, E.E.; Harper, D.R. A controlled clinical trial of a therapeutic bacteriophage preparation in chronic otitis due to antibiotic-resistant Pseudomonas aeruginosa; a preliminary report of efficacy. Clin. Otolaryngol. Allied Sci. 2009, 34, 349–357. [Google Scholar] [CrossRef] [PubMed]
  61. Kutateladze, M.; Adamia, R. Phage therapy experience at the Eliava Institute. Med. Mal. Infect. 2008, 38, 426–430. [Google Scholar] [CrossRef] [PubMed]
  62. Bruttin, A.; Brussow, H. Human volunteers receiving Escherichia coli phage T4 orally: A safety test of phage therapy. Antimicrob. Agents Chemother. 2005, 49, 2874–2878. [Google Scholar] [CrossRef] [Green Version]
  63. Sulakvelidze, A.; Alavidze, Z.; Morris, J.G. Bacteriophage therapy. Antimicrob. Agents Chemother. 2001, 45, 649–659. [Google Scholar] [CrossRef] [Green Version]
  64. Weber-Dabrowska, B.; Mulczyk, M.; Gorski, A. Bacteriophage therapy of bacterial infections: An update of our institutes’s experience. Arch. Immunol. Ther. Exp. 2000, 48, 547–551. [Google Scholar]
  65. Domrault Tanguy, C. Traitements Historiques des Infections Bactériennes par les Bactériophages: Adaptation Éventuelle aux Traitements des Pseudomonas aeruginosa Multirestsistants. Ph.D. Thesis, Faculte de Médecine de Nantes, Nantes, France, 1998. [Google Scholar]
  66. Cislo, M.; Dabrowski, M.; Weber-Dabrowska, B.; Woyton, A. Bacteriophage treatment of suppurative skin infections. Arch. Immunol. Ther. Exp. 1987, 35, 175–183. [Google Scholar]
  67. Pesce, E. Contribution à L’étude du Traitement des Furoncles et des Anthrax par le Bacteriophage. Ph.D. Thesis, University of Lyon Faculty of Medicine, Lyon, France, 1931. [Google Scholar]
  68. Little, J.S.; Dedrick, R.M.; Freeman, K.G.; Cristinziano, M.; Smith, B.E.; Benson, C.A.; Jhaveri, T.A.; Baden, L.R.; Solomon, D.A.; Hatfull, G.F. Bacteriophage treatment of disseminated cutaneous Mycobacterium chelonae infection. Nat. Commun. 2022, 13, 2313. [Google Scholar] [CrossRef]
  69. Doub, J.B.; Ng, V.Y.; Wilson, E.; Corsini, L.; Chan, B. Successful treatment of a recalcitrant Staphylococcus epidermidis prosthetic knee infection with intraoperative bacteriophage Therapy. Pharmaceuticals 2021, 14, 231. [Google Scholar] [CrossRef]
  70. Ferry, T.; Kolenda, C.; Batailler, C.; Gaillard, R.; Gustave, C.A.; Lustig, S.; Fevre, C.; Petitjean, C.; Leboucher, G.; Laurent, F.; et al. Case report: Arthroscopic “debridement antibiotics and implant retention” with local injection of personalized phage therapy to salvage a relapsing Pseudomonas aeruginosa prosthetic knee infection. Front. Med. 2021, 8, 569159. [Google Scholar] [CrossRef] [PubMed]
  71. Johri, A.V.; Johri, P.; Hoyle, N.; Pipia, L.; Nadareishvili, L.; Nizharadze, D. Chronic bacterial prostatitis treated with phage therapy after multiple failed antibiotic treatments–Case Report. Front. Pharmacol. 2021, 12, 692614. [Google Scholar] [CrossRef] [PubMed]
  72. Khatami, A.; Lin, R.C.Y.; Petrovic-Fabijan, A.; Alkalay-Oren, S.; Almuzam, S.; Britton, P.; Brownstein, M.; Dao, Q.; Fackler, J.; Hazan, R.; et al. Bacterial lysis, autophagy and innate immune responses during adjunctive phage therapy in a child. EMBO Mol. Med. 2021, 13, e13936. [Google Scholar] [CrossRef] [PubMed]
  73. Lebeaux, D.; Merabishvili, M.; Caudron, E.; Lannoy, D.; Van Simaey, L.; Duyvejonck, H.; Guillemain, R.; Thumerelle, C.; Podglajen, I.; Compain, F.; et al. A case of phage therapy against pandrug-resistant Achromobacter xylosoxidans in a 12-year-old lung-transplanted cystic fibrosis patient. Viruses 2021, 13, 60. [Google Scholar] [CrossRef]
  74. Paul, K.; Merabishvili, M.; Hazan, R.; Christner, M.; Herden, U.; Gelman, D.; Khalifa, L.; Yerushalmy, O.; Coppenhagen-Glazer, S.; Harbauer, T.; et al. Bacteriophage rescue therapy of a vancomycin-resistant Enterococcus faecium Infection in a one-year-old child following a third liver transplantation. Viruses 2021, 13, 1785. [Google Scholar] [CrossRef]
  75. Ramirez-Sanchez, C.; Gonzales, F.; Buckley, M.; Biswas, B.; Henry, M.; Deschenes, M.V.; Horne, B.; Fackler, J.; Brownstein, M.J.; Schooley, R.T.; et al. Successful treatment of Staphylococcus aureus prosthetic joint infection with bacteriophage therapy. Viruses 2021, 13, 1182. [Google Scholar] [CrossRef]
  76. Tan, X.; Chen, H.; Zhang, M.; Zhao, Y.; Jiang, Y.; Liu, X.; Huang, W.; Ma, Y. Clinical experience of personalized phage therapy against carbapenem-resistant Acinetobacter baumannii lung infection in a patient with chronic obstructive pulmonary disease. Front. Cell Infect. Microbiol. 2021, 11, 631585. [Google Scholar] [CrossRef]
  77. Wu, N.; Dai, J.; Guo, M.; Li, J.; Zhou, X.; Li, F.; Gao, Y.; Qu, H.; Lu, H.; Jin, J. Pre-optimized phage therapy on secondary Acinetobacter baumannii infection in four critical COVID-19 patients. Emerg. Microbes Infect. 2021, 10, 612–618. [Google Scholar] [CrossRef]
  78. Aslam, S.; Lampley, E.; Wooten, D.; Karris, M.; Benson, C.; Strathdee, S.; Schooley, R. Lessons learned from the first 10 consecutive cases of intravenous bacteriophage therapy to treat multidrug-resistant bacterial infections at a single center in the United States. Open Forum Infect. Dis. 2020, 7, ofaa389. [Google Scholar] [CrossRef]
  79. Bao, J.; Wu, N.; Zeng, Y.; Chen, L.; Li, L.; Yang, L.; Zhang, Y.; Guo, M.; Li, L.; Li, J.; et al. Non-active antibiotic and bacteriophage synergism to successfully treat recurrent urinary tract infection caused by extensively drug-resistant Klebsiella pneumoniae. Emerg. Microbes Infect. 2020, 9, 771–774. [Google Scholar] [CrossRef] [Green Version]
  80. Cano, E.J.; Caflisch, K.M.; Bollyky, P.L.; Van Belleghem, J.; Patel, R.; Fackler, J.; Brownstein, M.; Horne, B.; Biswas, B.; Henry, M.; et al. Phage therapy for limb-threatening prosthetic knee Klebsiella pneumoniae infection: Case report and in vitro characterization of anti-biofilm activity. Clin. Infect. Dis. 2021, 73, e144–e151. [Google Scholar] [CrossRef] [PubMed]
  81. Doub, J.B.; Ng, V.Y.; Johnson, A.J.; Slomka, M.; Fackler, J.; Horne, B.; Brownstein, M.; Henry, M.; Malagon, F.; Biswas, B. Salvage bacteriophage therapy for a chronic MRSA prosthetic joint infection. Antibiotics 2020, 9, 241. [Google Scholar] [CrossRef] [PubMed]
  82. Exarchos, V.; Tkhilaishvili, T.; Potapov, E.; Starck, C.; Trampuz, A.; Schoenrath, F. Successful bacteriophage treatment of infection involving cardiac implantable electronic device and aortic graft: A Trojan horse concept. Eur. Soc. Cardiol. 2020, 22, 597. [Google Scholar] [CrossRef] [PubMed]
  83. Ferry, T.; Kolenda, C.; Batailler, C.; Gustave, C.A.; Josse, J.; Laurent, F.; Batailler, C.; Lustig, S.; Malatray, M.; Petitjean, C. Phage Therapy as Adjuvant to Conservative Surgery and Antibiotics to Salvage Patients With Relapsing, S. aureus Prosthetic Knee Infection. Front. Med. 2020, 7, 570572. [Google Scholar] [CrossRef]
  84. Gainey, A.B.; Burch, A.K.; Brownstein, M.J.; Brown, D.; Fackler, J.; Horne, B.; Biswas, B.; Bivens, B.; Malagon, F.; Daniels, R. Combining bacteriophages with cefiderocol and meropenem/vaborbactam to treat a pan-drug resistant Achromobacter species infection in a pediatric cystic fibrosis patient. Pediatr. Pulmonol. 2020, 55, 2990–2994. [Google Scholar] [CrossRef]
  85. Mulzer, J.; Trampuz, A.; Potapov, E.V. Treatment of chronic left ventricular assist device infection with local application of bacteriophages. Eur. J. Cardiothorac. Surg. 2020, 57, 1003–1004. [Google Scholar] [CrossRef]
  86. Rostkowska, O.M.; Międzybrodzk, R.; Miszewska-Szyszkowska, D.; Górski, A.; Durlik, M. Treatment of recurrent urinary tract infections in a 60-year-old kidney transplant recipient. The use of phage therapy. Transpl. Infect. Dis. 2021, 23, e13391. [Google Scholar] [CrossRef]
  87. Rubalskii, E.; Ruemke, S.; Salmoukas, C.; Boyle, E.; Warnecke, G.; Tudorache, I.; Shrestha, M.; Schmitto, J.; Martens, A.; Rojas, S.; et al. Bacteriophage therapy for critical infections related to cardiothoracic surgery. Antibiotics 2020, 9, 232. [Google Scholar] [CrossRef]
  88. Aslam, S.; Pretorius, V.; Lehman, S.M.; Morales, S.; Schooley, R. Novel bacteriophage therapy for treatment of left ventricular assist device infection. J. Heart Lung Transplant. 2019, 38, 475–476. [Google Scholar] [CrossRef]
  89. Aslam, S.; Courtwright, A.M.; Koval, C.; Lehman, S.; Morales, S.; Langlais Furr, C.L.; Rosas, F.; Brownstein, M.; Fackler, J.; Sisson, B.; et al. Early clinical experience of bacteriophage therapy in three lung transplant recipients. Am. J. Transplant. 2019, 19, 2631–2639. [Google Scholar] [CrossRef]
  90. Corbellino, M.; Kieffer, N.; Kutateladze, M.; Balarjishvili, N.; Leshkasheli, L.; Askilashvili, L.; Tsertsvadze, G.; Rimoldi, S.G.; Nizharadze, D.; Hoyle, N.; et al. Eradication of a multi-drug resistant, carbapenemase-producing Klebsiella pneumoniae isolate following oral and intra-rectal therapy with a custom-made, lytic bacteriophage preparation. Clin. Infect. Dis. 2020, 70, 1998–2001. [Google Scholar] [CrossRef] [PubMed]
  91. Dedrick, R.M.; Guerrero-Bustamante, C.A.; Garlena, R.A.; Russell, D.; Ford, K.; Harris, K.; Gilmour, K.; Soothill, J.; Jacobs-Sera, D.; Schooley, R.; et al. Engineered bacteriophages for treatment of a patient with a disseminated drug-resistant Mycobacterium abscessus. Nat. Med. 2019, 25, 730–733. [Google Scholar] [CrossRef] [PubMed]
  92. Duplessis, C.A.; Stockelman, M.; Hamilton, T.; Merril, G.; Brownstein, M.; Bishop-lilly, K.; Schooley, R.; Henry, M.; Horne, B.; Sisson, B.; et al. A case series of emergency investigational new drug applications for bacteriophages treating recalcitrant multi-drug resistant bacterial infections: Confirmed safety and a signal of efficacy. J. Intensive Crit. Care 2019, 5, 11. [Google Scholar]
  93. Djebara, S.; Maussen, C.; De Vos, D.; Merabishvili, M.; Damanet, B.; Win Pang, K.; De Leenheer, P.; Strachinaru, I.; Soentjens, P.; Pirnay, J.P. Processing phage therapy requests in a brussels military hospital: Lessons identified. Viruses 2019, 11, 265. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  94. Gilbey, T.; Ho, J.; Cooley, L.A.; Fabijan, A.P.; Iredell, J. Adjunctive bacteriophage therapy for prosthetic valve endocarditis due to Staphylococcus aureus. Med. J. Aust. 2019, 211, 142–143.e1. [Google Scholar] [CrossRef] [Green Version]
  95. Kuipers, S.; Ruth, M.M.; Mientjes, M.; de Sévaux, R.; van Ingen, J. Successful treatment of chronic relapsing urinary tract infection with bacteriophages in a renal transplant recipient-a Dutch case report. Antimicrob. Agents Chemother. 2019, 20, e01281-19. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  96. Law, N.; Logan, C.; Yung, G.; Langlais Furr, C.L.; Lehman, S.; Morales, S.; Rosas, F.; Gaidamaka, A.; Bilinsky, I.; Grint, P. Successful adjunctive use of bacteriophage therapy for treatment of multidrug-resistant Pseudomonas aeruginosa infection in a cystic fibrosis patient. Infection 2019, 47, 665–668. [Google Scholar] [CrossRef]
  97. Maddocks, S.; Petrovic-Fabijan, A.; Ho, J.; Lin, R.; Ben Zakour, N.; Dugan, C.; Kliman, I.; Branston, S.; Morales, S. Bacteriophage therapy of ventilator-associated pneumonia and empyema caused by Pseudomonas aeruginosa. Am. J. Respir. Crit. Care Med. 2019, 200, 1179–1181. [Google Scholar] [CrossRef]
  98. Nir-Paz, R.; Gelman, D.; Khouri, A.; Sisson, B.M.; Fackler, J.; Alkalay-Oren, S.; Khalifa, L.; Rimon, A.; Yerushalmy, O.; Bader, R.; et al. Successful treatment of antibiotic resistant polymicrobial bone infection with bacteriophages and antibiotics combination. Clin. Infect. Dis. 2019, 69, 2015–2018. [Google Scholar] [CrossRef]
  99. Onsea, J.; Soentjens, P.; Djebara, S.; Merabishvili, M.; Depypere, M.; Spriet, I.; De Munter, P.; Debaveye, Y.; Nijs, S.; Vanderschot, P.; et al. Bacteriophage application for difficult-to-treat musculoskeletal infections: Development of a standardized multidisciplinary treatment protocol. Viruses 2019, 11, 891. [Google Scholar] [CrossRef] [Green Version]
  100. Tkhilaishvili, T.; Winkler, T.; Muller, M.; Perkaa, C.; Trampuz, A. Bacteriophages as adjuvant to antibiotics for the treatment of periprosthetic joint infection caused by multidrug-resistant Pseudomonas aeruginosa. Antimicrob. Agents Chemother. 2019, 64, e00924-19. [Google Scholar] [CrossRef] [Green Version]
  101. Aslam, S.; Gilbey, T.; Maddocks, S.; Morales, S.; Lehman, S.; Branston, S.; Fabijan, A.P.; Langlais Furr, C.L.; Rosas, F.; Bilinsky, I.; et al. Safety and efficacy of bacteriophage therapy: Analysis of clinical case. Open Forum Infect. Dis. 2018, 5, S47. [Google Scholar] [CrossRef]
  102. Aslam, S.; Yung, J.; Dan, S.; Reed, S.; LeFebvre, M.; Logan, C.; Taplitz, R.; Law, N.; Golts, E.; Afshar, K.; et al. Bacteriophage Treatment in a Lung Transplant Recipient. J. Heart Lung Transplant. 2018, 37, S155–S156. [Google Scholar] [CrossRef]
  103. Chan, B.K.; Turner, P.E.; Kim, S.; Mojibian, H.; Elefteriades, J.; Narayan, D. Phage treatment of an aortic graft infected with Pseudomonas aeruginosa. Evol. Med. Public Health 2018, 2018, 60–66. [Google Scholar] [CrossRef] [Green Version]
  104. Ferry, T.; Leboucher, G.; Fevre, C.; Herry, Y.; Conrad, A.; Josse, J.; Batailler, C.; Chidiac, C.; Medina, M.; Lustig, S.; et al. Salvage Debridement, Antibiotics and Implant Retention (“DAIR”) With Local Injection of a Selected Cocktail of Bacteriophages: Is It an Option for an Elderly Patient with Relapsing Staphylococcus aureus Prosthetic Joint Infection? Open Forum Infect. Dis. 2018, 5, ofy269. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  105. Ferry, T.; Boucher, F.; Fevre, C.; Perpoint, T.; Château, J.; Petitjean, C.; Josse, J.; Chidiac, C.; L’hostis, G.; Leboucher, G.; et al. Innovations for the treatment of a complex bone and joint infection due to XDR Pseudomonas aeruginosa including local application of a selected cocktail of bacteriophages. J. Antimicrob. Chemother. 2018, 73, 2901–2903. [Google Scholar] [CrossRef] [Green Version]
  106. Fish, R.; Kutter, E.; Wheat, G.; Blasdel, B.; Kutateladze, M.; Kuhl, S. Compassionate Use of Bacteriophage Therapy for Foot Ulcer Treatment as an Effective Step for Moving Toward Clinical Trials. Methods Mol. Biol. 2018, 1693, 159–170. [Google Scholar] [CrossRef]
  107. Fish, R.; Kutter, E.; Bryan, D.; Wheat, G.; Kuhl, S. Resolving Digital Staphylococcal Osteomyelitis Using Bacteriophage-A Case Report. Antibiotics 2018, 7, 87. [Google Scholar] [CrossRef] [Green Version]
  108. Hoyle, N.; Zhvaniya, P.; Balarjishvili, N.; Bolkvadze, D.; Nadareishvili, L.; Nizharadze, D.; Wittmann, J.; Rohde, C.; Kutateladze, M. Phage therapy against Achromobacter xylosoxidans lung infection in a patient with cystic fibrosis: A case report. Res. Microbiol. 2018, 169, 540–542. [Google Scholar] [CrossRef]
  109. LaVergne, S.; Hamilton, T.; Biswas, B.; Kumaraswamy, M.; Schooley, R.T.; Wooten, D. Phage therapy for a multidrug-resistant Acinetobacter baumannii craniectomy site infection. Open Forum Infect. Dis. 2018, 5, ofy064. [Google Scholar] [CrossRef] [Green Version]
  110. Patey, O.; McCallin, S.; Mazure, H.; Liddle, M.; Smithyman, A.; Dublanchet, A. Clinical indications and compassionate use of phage therapy: Personal experience and literature review with a focus on osteoarticular infections. Viruses 2018, 11, 18. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  111. Ujmajuridze, A.; Chanishvili, N.; Goderdzishvili, M.; Leitner, L.; Mehnert, U.; Chkhotua, A.; Kessler, T.; Sybesma, W. Adapted Bacteriophages for Treating Urinary Tract Infections. Front. Microbiol. 2018, 9, 1832. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  112. Duplessis, C.; Biswas, B.; Hanisch, B.; Perkins, M.; Henry, M.; Quinones, J.; Wolfe, D.; Estrella, L.; Hamilton, T. Refractory Pseudomonas Bacteremia in a 2-Year-Old Sterilized by Bacteriophage Therapy. J. Pediatric Infect. Dis. Soc. 2018, 7, 253–256. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  113. Jennes, S.; Merabishvili, M.; Soentjens, P.; Pang, K.W.; Rose, T.; Keersebilck, E.; Soete, O.; François, P.M.; Teodorescu, S.; Verween, G.; et al. Use of bacteriophages in the treatment of colistin-only-sensitive Pseudomonas aeruginosa septicaemia in a patient with acute kidney injury-a case report. Crit. Care 2017, 21, 129. [Google Scholar] [CrossRef] [Green Version]
  114. Kiladze, N.; Chanishvili, N.; Shulaia, T.; Bendeliani, Z.; Zaichenko, Y. Phages in treatment of some deep skin purulent infections. Lviv Clin. Bull. 2017, 2, 39–43. [Google Scholar] [CrossRef]
  115. Schooley, R.T.; Biswas, B.; Gill, J.J.; Hernandez-Morales, A.; Lancaster, J.; Lessor, L.; Barr, J.J.; Reed, S.L.; Rohwer, F.; Benler, S.; et al. Development and use of personalized bacteriophage-based therapeutic cocktails to treat a patient with a disseminated resistant Acinetobacter baumannii infection. Antimicrob. Agents Chemother. 2017, 61, e00954-17. [Google Scholar] [CrossRef] [Green Version]
  116. Totté, J.E.E.; van Doorn, M.B.; Pasmans, S.G.M.A. Successful treatment of chronic Staphylococcus aureus-related dermatoses with the topical endolysin staphefekt sa.100: A report of 3 cases. Case Rep. Dermatol. 2017, 9, 19–25. [Google Scholar] [CrossRef]
  117. Zhvania, P.; Hoyle, N.S.; Nadareishvili, L.; Nizharadze, D.; Kutateladze, M. Phage therapy in a 16-year-old boy with Netherton syndrome. Front. Cell. Infect. Microbiol. 2017, 4, 94. [Google Scholar] [CrossRef] [Green Version]
  118. Fish, R.; Kutter, E.; Wheat, G.; Blasdel, B.; Kutateladze, M.; Kuhl, S. Bacteriophage treatment of intransigent diabetic toe ulcers: A case series. J. Wound Care 2016, 25, S27–S33. [Google Scholar] [CrossRef]
  119. Ujmajuridze, A.; Jvania, G.; Chanishvili, N.; Goderdzishvili, M.; Sybesma, W.; Managadze, L.; Chkhotua, A.; Kessler, T. Phage therapy for the treatment for urinary tract infection: Results of in-vitro screenings and in-vivo application using commercially available bacteriophage cocktails. Eur. Urol. Suppl. 2016, 15, e265. [Google Scholar] [CrossRef]
  120. Fadlallah, A.; Chelala, E.; Legeais, J.M. Corneal infection therapy with topical bacteriophage administration. Open Ophthalmol. J. 2015, 9, 167–168. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  121. Rose, T.; Verbeken, G.; De Vos, D.; Merabishvili, M.; Vaneechoutte, M.; Lavigne, R.; Jennes, S.; Zizi, M.; Pirnay, J.P. Experimental phage therapy of burn wound infection: Difficult first steps. Int. J. Burns Trauma 2014, 4, 66–73. [Google Scholar] [PubMed]
  122. Khawaldeh, A.; Morales, S.; Dillon, B.; Alavidze, Z.; Ginn, A.N.; Thomas, L.; Chapman, S.J.; Dublanchet, A.; Smithyman, A.; Iredell, J.R. Bacteriophage therapy for refractory Pseudomonas aeruginosa urinary tract infection. J. Med. Microbiol. 2011, 60, 1697–1700. [Google Scholar] [CrossRef] [PubMed]
  123. Kvachadze, L.; Balarjishvili, N.; Meskhi, T.; Tevdoradze, E.; Skhirtladze, N.; Pataridze, T.; Adamia, R.; Topuria, T.; Kutter, E.; Rohde, C. Evaluation of lytic activity of staphylococcal bacteriophage Sb-1 against freshly isolated clinical pathogens. Microb. Biotechnol. 2011, 4, 643–650. [Google Scholar] [CrossRef] [Green Version]
  124. Patey, O.; Asselineau, A.; Dublanchet, A. Traitement par Phagothérapie de Deux Ostéites Chroniques en Échec Thérapeutique. In Proceedings of the 11ème Journées Nationales d’Infectiologie, Montpellier, France, 2010. [Google Scholar]
  125. Górski, A.; Targonska, M.; Borysowski, J.; Weber-Dabrowska, B. The potential of phage therapy in bacterial infections of the eye. Ophthalmologica 2009, 223, 162–165. [Google Scholar] [CrossRef]
  126. Letkiewicz, S.; Miedzybrodzki, R.; Fortuna, W.; Weber-Dabrowska, B.; Górski, A. Eradication of Enterococcus faecalis by phage therapy in chronic bacterial prostatitis-case report. Folia Microbiol. 2009, 54, 457–461. [Google Scholar] [CrossRef]
  127. Miedzybrodzki, R.; Fortuna, W.; Weber-Dabrowska, B.; Górski, A. A retrospective analysis of changes in inflammatory markers in patients treated with bacterial viruses. Clin. Exp. Med. 2009, 9, 303–312. [Google Scholar] [CrossRef]
  128. Dublanchet, A.; (Intermunicipal hospital center of Villeneuve-Saint-Georges, Villeneuve-Saint-Georges, France); Ketari, M.; (Intermunicipal hospital center of Villeneuve-Saint-Georges, Villeneuve-Saint-Georges, France). Otite externe à staphylocoque doré traitée par les bacteriophages, 2007. Unpublished work.
  129. Duez, J.M.; (University hospital center of Dijon); Dupret-Louzeau, A.M.; (University hospital center of Dijon); Neuwirth, C.; (University hospital center of Dijon). Case report od phagetherapy of a P. aeruginosa pulmonary infected patient, 2007. Unpublished work.
  130. Leszczynski, P.; Weber-Dabrowska, B.; Kohutnicka, M.; Luczak, M.; Górecki, A.; Górski, A. Successful eradication of methicillin-resistant Staphylococcus aureus (MRSA) intestinal carrier status in a healthcare worker-case report. Folia Microbiol. 2006, 51, 236–238. [Google Scholar] [CrossRef]
  131. Marza, J.; Soothill, J.; Boydell, P.; Collyns, T.A. Multiplication of therapeutically administered bacteriophages in Pseudomonas aeruginosa infected patients. Burns 2006, 32, 644–666. [Google Scholar] [CrossRef]
  132. Weber-Dabrowska, B.; Zimecki, M.M.K.; Kochanowska, I.; Kochanowska, I.; Lusiak-Szelachowska, M. Alternative therapies in antibiotic-resistant infection. Adv. Med. Sci. 2006, 51, 242–244. [Google Scholar]
  133. Jikia, D.; Chkhaidze, N.; Imedashvili, E.; Mgaloblishvili, I.; Tsitlanadze, G.; Katsarava, R.; Glenn Morris, J.; Sulakvelidze, A. The use of a novel biodegradable preparation capable of the sustained release of bacteriophages and ciprofloxacin, in the complex treatment of multidrug-resistant Staphylococcus aureus-infected local radiation injuries caused by exposure to Sr90. Clin. Exp. Dermatol. 2005, 30, 23–26. [Google Scholar] [CrossRef] [PubMed]
  134. Weber-Dabrowska, B.; Mulczyk, M.; Gorski, A. Bacteriophages as an efficient therapy for antibiotic-resistant septicemia in man. Transplant. Proc. 2003, 35, 1385–1386. [Google Scholar] [CrossRef] [PubMed]
  135. Markoishvili, K.; Tsitlanadze, G.; Katsarava, R.; Morris, J.G.; Sulakvelidze, A. A novel sustained-release matrix based on biodegradable poly(ester amide)s and impregnated with bacteriophages and an antibiotic shows promise in management of infected venous stasis ulcers and other poorly healing wounds. Int. J. Dermatol. 2002, 41, 453–458. [Google Scholar] [CrossRef] [PubMed]
  136. Weber-Dabrowska, B.; Mulczyk, M.; Gorski, A. Bacteriophage therapy for infections in cancer patients. Clin. Appl. Immunol. Rev. 2001, 1, 4. [Google Scholar] [CrossRef]
  137. Abdul-Hassan, H.S.; El-Tahan, K.; Massoud, B.; Gomaa, R. Bacteriophage therapy of Pseudomonas burn wound sepsis. Ann. Med. Burn. Club 1990, 3, 262–264. [Google Scholar]
  138. Slopek, S.; Weber Dabrowska, B.; Dabrowski, M.; Kucharewicz-Krukowska, A. Results of bacteriophage treatment of suppurative bacterial infections in the years 1981–1986. Arch. Immunol. Ther. Exp. 1987, 37, 69–83. [Google Scholar]
  139. Slopek, S.; Kucharewicz-Krukowska, A.; Weber-Dabrowska, B.; Dabrowski, M. Results of bacteriophage treatment of suppurative bacterial infections. VI. Analysis of treatment of suppurative staphylococcal infections. Arch. Immunol. Ther. Exp. 1985, 33, 261–273. [Google Scholar]
  140. Slopek, S.; Kucharewicz-Krukowska, A.; Weber-Dabrowska, B.; Dabrowski, M. Results of bacteriophage treatment of suppurative bacterial infections. V. Evaluation of the results obtained in children. Arch. Immunol. Ther. Exp. 1985, 33, 241–359. [Google Scholar]
  141. Slopek, S.; Kucharewicz-Krukowska, A.; Weber-Dabrowska, B.; Dabrowski, M. Results of bacteriophage treatment of suppurative bacterial infections. IV. Evaluation of results obtained in 370 cases. Arch. Immunol. Ther. Exp. 1985, 33, 219–240. [Google Scholar]
  142. Slopek, S.; Durlakowa, I.; Weber-Dabrowska, B.; Dabrowski, M.; Kucharewicz-Krukowska, A. Results of bacteriophage treatment of suppurative bacterial infections. III. Detailed evaluation of the results obtained in further 150 cases. Arch. Immunol. Ther. Exp. 1984, 32, 317–335. [Google Scholar]
  143. Slopek, S.; Durlakova, I.; Weber-Dabrowska, B.; Kucharewicz-Krukowska, A.; Dabrowski, M.; Bisikiewicz, R. Results of bacteriophage treatment of suppurative bacterial infections. I. General evaluation of the results. Arch. Immunol. Ther. Exp. 1983, 31, 267–291. [Google Scholar]
  144. Kress, D.W.; Graham, W.P.; Davis, T.S.; Miller, S.H. A preliminary report on the use of Staphage Lysate for treatment of hidradenitis suppurativa. Ann. Plast. Surg. 1981, 6, 393–395. [Google Scholar] [CrossRef] [PubMed]
  145. Lang, G.; Kher, P.; Mathevon, H. Bactériophages et chirurgie orthopédique-A propos de sept cas. Rev. Chir. Orthop. Reparatrice Appar. Mot. 1979, 65, 33–37. [Google Scholar] [PubMed]
  146. Grimont, P.A.D.; Grimont, F.; Lacut, J.Y.; Issanchou, A.M.; Aubertin, J. Traitement d’une endocardite à Serratia par les bactériophages (lettre). Nouv. Presse Méd. 1978, 7, 225. [Google Scholar]
  147. Marcuk, L.M.; Nikiforov, V.N.; Scerbak, J.F.; Levitov, T.A.; Kotljarova, R.I.; Naumsina, M.S.; Davydov, S.U.; Monsur, K.A.; Rahman, M.A.; Latif, M.A. Clinical studies of the use of bacteriophage in the treatment of cholera. Bull. World Health Organ. 1971, 45, 77–83. [Google Scholar]
  148. Courtieu, A.L.; Duboeuf, C.; Bogenmann, J.; Maka, G.; Longeray, C. Gastro-entérite à rechute par une Salmonella panama devenant résistante aux antibiotiques utilisés. Stérilisation par les bactériophages. J. Méd. Lyon 1965, 46, 1481–1486. [Google Scholar]
  149. Devaux, G. La prophylaxie des gastro-entérites infantiles. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1962. [Google Scholar]
  150. Bertoye, A.; Courtieu, A.L. Traitement des infections à bacilles pyocyaniques par des bactériophages adaptés par sélection. J. Méd. Lyon 1960, 41, 739–751. [Google Scholar]
  151. Bertoye, A.; Gaillard, L.; Courtieu, A.L. Les bactériophages adaptés dans le traitement des infections à germes résistants aux antibiotiques. J. Méd. Lyon 1959, 40, 465–471. [Google Scholar]
  152. Martin, P. Méningite post-traumatique à pyocyaniques traitée par un bactériophage adapté intrarachidien. Acta Chir. Belg. 1959, 58, 85–90. [Google Scholar]
  153. Sedallian, P.; Bertoye, A.; Gauthier, J.; Muller, J.M.; Courtieu, A.L. Méningite purulente à colibacilles traitée par un bactériophage adapté intrarachidien. Lyon Méd. 1958, 90, 509–512. [Google Scholar]
  154. Raiga, A. La phagothérapie pré-opératoire. Guérison des ostéites fistulisées. Résultats éloignés de 10 et 11 ans. Bull. Mémoires Société Chir. Paris 1953, 43, 164. [Google Scholar]
  155. Feihl, J.P. La Thérapeutique des Staphylococcies par le Bacteriophage. Ph.D. Thesis, Université de Lausanne, Lausanne, Switzerland, 1949. [Google Scholar]
  156. Pouch, R.M. Contribution à L’étude de la Nature et du Traitement par le Bactériophage des Abcès de la Marge de L’anus. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1949. [Google Scholar]
  157. Raiga, A. Guérison d’un phlegmon staphylococcique de la paume de la main par la phagothérapie, sans intervention chirurgicale, avec conservation intégrale des mouvements. Bull. Mémoires Société Chir. Paris 1948, 38, 238. [Google Scholar]
  158. MacNeal, W.J.; Blevins, A.; McGrath, R. Septic staphylococcemia successfully treated by penicillin and bacteriophage. Arch. Intern. Med. 1947, 79, 391–400. [Google Scholar] [CrossRef] [PubMed]
  159. Knouf, E.G.; Ward, W.E.; Reichle, P.A.; Bower, A.G.; Hamilton, P. Treatment of typhoid fever with type specific bacteriophage. JAMA 1946, 132, 134–138. [Google Scholar] [CrossRef]
  160. MacNeal, W.J.; Filak, L.; Blevins, A. Conjoined action of penicillin and bacteriophages. J. Lab. Clin. Med. 1946, 31, 974–981. [Google Scholar]
  161. MacNeal, W.J.; Poindexter, C.A.; Marty, F.N. Apparent arrest of staphylococcal endocarditis. Am. Heart, J. 1945, 29, 403–408. [Google Scholar] [CrossRef]
  162. Recoules-Arché, J.L. Emploi du Bactériophage de D’hérelle dans la Prophylaxie et le Traitement des Infections Cutanées. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1945. [Google Scholar]
  163. MacNeal, W.J.; Frisbee, F.C.; Blevins, A. Bacteriophage therapy of staphylococcic septic obstruction of cavernous sinus: II. Report of cases. Arch. Ophthalmol. 1943, 29, 341–368. [Google Scholar] [CrossRef]
  164. MacNeal, W.J.; Frisbee, F.C.; Blevins, A. Recoveries of staphylococcic meningitis following bacteriophage therapy. Arch. Otolaryngol. 1943, 37, 507–525. [Google Scholar] [CrossRef]
  165. MacNeal, W.J.; Frisbee, F.C.; McRae, M.A. Staphylococcemia 1931 to 1940: Five hundred patients. Am. J. Clin. Pathol. 1942, 12, 281–294. [Google Scholar] [CrossRef]
  166. MacNeal, P.S.; Foster, D.B. Staphylococci (Staph. aureus) meningitis treated with asparagin bacteriophage; two cases. Am. J. Med. Sci. 1941, 202, 874–879. [Google Scholar] [CrossRef]
  167. MacNeal, W.J. Recent developments in bacteriophage therapy (staphylococci). N. Y. State J. Med. 1941, 41, 1531–1536. [Google Scholar]
  168. MacNeal, W.J. Bacteriophage therapy; specific therapeutic shoc-hugh young reaction. Arch. Surg. 1941, 43, 579. [Google Scholar] [CrossRef]
  169. Raiga, A. Traitement des Plaies de Guerre par le Bactériophage de d’Hérelle; Amédée Legrand et Jean Bertrand: Paris, France, 1941. [Google Scholar]
  170. Longacre, A.B.; Zaytzeff-Jern, H.; Meleney, F.L. Treatment of Staphylococcic septicemia with bacteriophage. Surg. Gynecol. Obs. 1940, 70, 1–11. [Google Scholar]
  171. MacNeal, W.J. Use of asparagin bacteriophage in treatment of acute hematogenous osteomyelitis. Surg. Gynecol. Obs. 1940, 71, 766. [Google Scholar]
  172. Huet, F. Traitement des Abcès du sein par le Bactériophage Anti-Staphylococcique. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1938. [Google Scholar]
  173. Batier, H. Etude de la Bactériophagie dans le Traitement de la Colibacilloses. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1937. [Google Scholar]
  174. Burnet, W.M.; Salberg, J.B. Gonorrhea in female: Report of series of cases treated with gonococcus lysate. Am. J. Syph. Gonor Ven. Dis. 1937, 2, 64–71. [Google Scholar]
  175. Gross, A. Des Septicémies à Staphylocoques (Formes Chirurgicales, Ostéomyélites Exceptées) et de leur Traitement par le Bactériophage Intraveineux. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1937. [Google Scholar]
  176. MacNeal, W.J. The infectious organism in osteomyelitis: Part II. Bacteriophage and Serum Therapy. J. Bone Jt. Surg. 1937, 19, 891–903. [Google Scholar]
  177. Raiga, A. Les inoculations intraveineuses de bactériophage. Quelques enseignements fournis par l’étude de 106 cas d’ostéomyélite et de septicémie staphylococciques. Concours Méd. 1937, 12, 905–909. [Google Scholar]
  178. Raiga, A. Guérison par la phagothérapie d’une ostéomyélite aiguë continuant à évoluer malgré trois opérations chirurgicales successives. Bull. Mémoires Société Chir. Paris 1937, 29, 42. [Google Scholar]
  179. Raiga, A. Deux septicémies à staphylocoque guéries depuis quatre et cinq ans. Le processus de la guérison naturelle et son utilisation thérapeutique. Société des Chirurgiens de Paris 1937, 102–113. [Google Scholar]
  180. Thimonnier, A.R. Traitement de Quelques Affections Cutanées par le Bacteriophage. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1937. [Google Scholar]
  181. Bréhant, J. Septicopyohémie à staphylocoque doré, Bactériophage intraveineux. Guérison. Bull. Mémoires Société Natl. Chir. 1936, 62, 1110–1111. [Google Scholar]
  182. Donadieu, R. Le Traitement des infections à staphylocoques par le bactériophage. Ph.D. Thesis, Université de Toulouse, Faculté de Médecine, Toulouse, France, 1936. [Google Scholar]
  183. Du Buit, H. Traitement des Méningites Aiguës par le Bactériophage, Étude Clinique et Expérimentale. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1936. [Google Scholar]
  184. MacNeal, W.J.; Frisbee, F.C. Bacteriophage service to patients with Staphylococcus septicemia. Am. J. Med. 1936, 191, 170–178. [Google Scholar] [CrossRef]
  185. Ward, J.; MacNeal, W.J. One hundred patients with Staphylococcus septicemia receiving bacteriophage service. Am. J. Med. 1936, 191, 179–195. [Google Scholar]
  186. Marion, J. Principes, indications et résultats du traitement des furoncles et anthrax par le bactériophage. Lyon Médical 1936, 158, 2–10. [Google Scholar]
  187. Morrison, S.; Gardner, R.E. The treatment of a lung abscess due to bacillus coli with a lytic filtrate. JAMA 1936, 107, 33. [Google Scholar] [CrossRef]
  188. Raiga, A. Modifications apportées à l’évolution d’un abcès polymicrobien du poumon par une injection intra-veineuse de bactériophage. Bull. Mémoires Société Chir. Paris 1936. [Google Scholar]
  189. Artarit, G. Traitement des Septicémies Staphylococciques par les Injections Intra-Veineuses de Bactériophage de d’Hérelle. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1935. [Google Scholar]
  190. Dunlap, J.E. Staphylococcic meningitis with recovery. JAMA 1935, 104, 1594–1595. [Google Scholar] [CrossRef]
  191. Hamilton, R.L. Sepitcemia. Guthrie Clin. Butletin 1935, 1, 778. [Google Scholar]
  192. Lampert, R.; Boyce, F.F.; McFetridge, E.M. Bacteriophage Therapy. A Clinical study, with special reference to the technique of application. Am. J. Surg. 1935, 29, 435–443. [Google Scholar]
  193. Mériel. Septico-pyohémie Mortelle à Staphylocoque, Suite d’anthrax du dos. Concours Med. 1935, 35, 620–622. Available online: https://gallica.bnf.fr/ark:/12148/bpt6k5417843x/f16.item (accessed on 24 February 2023).
  194. Moore, D.C.; Blinn, A.B.; MacNeal, W.J. Compound fracture complicated by prolonged Streptococcus and Staphylococcus septicemia, with recovery. Am. J. Surg. 1935, 29c, 143–148. [Google Scholar] [CrossRef]
  195. Pretty, H.G. Bacteriophage in the injection treatment of carbuncles, and allied superficial infections. Can. Med. Assoc. J. 1935, 32, 24–29. [Google Scholar] [PubMed]
  196. Récamier, J.; Sobieski, E. Un cas grave de septicémie à staphylocoque guéri par la bactériophage intraveineux. Bull. Mémoires Société Natl. Chir. 1935, 61, 60. [Google Scholar]
  197. Thibairenq, H. Bactériothérapie Locale par le Bacteriophage. Ph.D. Thesis, Université de Montpellier, Faculté de Médecine, Montpellier, France, 1935. [Google Scholar]
  198. Wehrbein, H.L.; Nerb, L. Bacteriophage in the treatment of urinary infections. With an appendix on the technique of phage preparation. Am. J. Surg. 1935, 29, 48–53. [Google Scholar] [CrossRef]
  199. MacNeal, W.J. Specific treatment of septic infections, particularly with aid of bacteriophage. Am. J. Med. Sci. 1934, 184, 623–634. [Google Scholar] [CrossRef]
  200. MacNeal, W.J.; Frisbee, F.C.; Applebaum, M. II. Use of bacteriophages in treatment of colon bacillus infections of the urinary tract. Arch. Surg. 1934, 29, 633–642. [Google Scholar] [CrossRef]
  201. MacNeal, W.J.; Frisbee, F.C.; Applebaum, M. III. Bacteriophages in treatment of colon bacillus septicemia. Arch. Surg. 1934, 29, 741–747. [Google Scholar]
  202. MacNeal, W.J.; Frisbee, F.C.; Applebaum, M. IV. Bacteriophages in chronic colitis of undetermined causation and in intestinal fistulas. Arch. Surg. 1934, 29, 748–758. [Google Scholar] [CrossRef]
  203. Raiga, A. Guérison d’une artrite purulente du genou à streptocoque et tétragène par une inoculation intra-articulaire de Bactériophage. Bull. Mémoires Société Chir. Paris 1934, 26, 463–466. [Google Scholar]
  204. Raiga, A. Guérison par une inoculation intra-veineuse de bactériophage, d’une pyohémie à staphylocoque. Bull. Mémoires Société Chir. Paris 1934, 26, 555–568. [Google Scholar]
  205. Raiga, A. Deux cas de colite aiguë post-opératoire traités par le bactériophage. Bull. Et Mémoires De La Société Des Chir. De Paris 1934, 405–411. [Google Scholar]
  206. Rosen, T. Contribution à la Thérapeutique du Furoncle de la Lèvre Supérieure, son Traitement par le Bacteriophage. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1934. [Google Scholar]
  207. Salmon, M.; Bouyala, J. Arthrite purulente du genou traitée par la bacté-phagothérapie et l’arthrotomie. Bull. Société Chir. Marseille 1934, 8, 1–3. [Google Scholar]
  208. Zaytzeff-Jern, H.; Howes, E.L.; Meleney, F.L. Studies in bacteriophage, I. The behavior of the bacteriophage and the bacteria in the lesion after the treatment of acute Staphylococcus skin infections with bacteriophage. J. Lab. Clin. Med. 1934, 19, 12. [Google Scholar]
  209. Albee, F.H. The treatment of osteomyelitis by bacteriophage. J. Bone Jt. Surg. 1933, 15, 58–66. [Google Scholar]
  210. Botoiana; Stoiana; Costaesco. Les bactériophages en chirurgie. Bull. Mémoires Société Natl. Chir. 1933, 58, 1506–1507. [Google Scholar]
  211. Boyce, F.F.; Lampert, R.; McFetridge, E.M. Bacteriophagy in the treatment of infections of the superficial and deep tissues, with report of 200 cases. New Orleans Med. Surg. J. 1933, 86, 158–165. [Google Scholar]
  212. Gernez, C.; Breton, A. Contribution au traitement des fièvres typho-paratyphiques par le principe lytique transmissible (ou bactériophage) anti-Éberth préparé par électrophorèse. Presse Méd. 1933, 41, 580–582. [Google Scholar]
  213. Ilieff, J. Contribution à l’étude des affections staphylococciques de la face: Leur traitement par le bactériophage. Ph.D. Thesis, Université de Nancy, Faculté de Médecine, Nancy, France, 1933. [Google Scholar]
  214. Dechaume, M.; Mahé, H. Ostéomyélite du maxillaire supérieur chez un nourrisson de deux mois et demi, traitement par des injections locales de bacté-staphyphage, guérison. Rev. Stomatol. 1933, 35, 275. [Google Scholar]
  215. Mazzuca, P. Contribution à L’étude du Bactériophage, son Emploi en Injections Intraveineuses au Cours de Quelques Septicémies et de Certaines Infections. Ph.D. Thesis, Université d’Alger, Faculté mixte de Médecine et de Pharmacie, Alger, Algérie, France, 1933. [Google Scholar]
  216. Raiga, A. Guérison d’une ostéomyélite prolongée avec arthrite coxofémorale tardive, par une inoculation intraveineuse de Bactériophage. Mutation réversible d’un staphylocoque en streptocoque. Bull. Mémoires Société Chir. Paris 1933, 25, 484. [Google Scholar]
  217. Raiga, A. Guérison par une inoculation intra-veineuse de Bactériophage d’une septicémie à staphylocoque compliquée d’une ostéomyélite à deux foyers, corporéal et lamellaire. Bull. Mémoires Société Chir. Paris 1933, 25, 555. [Google Scholar]
  218. Raiga, A. Deux cas de parotidite aiguë post-opératoire traités par le bactériophage. Bull. Mémoires Société Chir. Paris 1933, 25, 329–338. [Google Scholar]
  219. Ruddell, K.R.; Sicks, O.W.; Loomis, N.S. Observations of the use of bacterial lysates in surgical cases. Am. J. Surg. 1933, 22, 337–342. [Google Scholar] [CrossRef]
  220. Sauvé, L. Un cas de très haute gravité de staphylococcie guérie par des injections intra-veineuses de bactériophage. Concours Med. 1933, 34, 180–181. [Google Scholar]
  221. Bagley, E.C.; Keller, M. Bacteriophage in the treatment of osteomyelitis. A study of ten cases, including three cases complicated by Staphylococcus aureus septicemia. In Proceedings of the Scientific Proceedings of the Thirty-Second Annual Meeting of the American Association of the Pathologists and Bacteriologist, Phladelphia, PA, USA, 18–29 April 1932. [Google Scholar]
  222. Boudet, E. Du traitement de la pyélonéphrite gravidique par le bactériophage de d’Hérelle. Ph.D. Thesis, Université de Montpellier, Faculté de Médecine, Montpellier, France, 1932. [Google Scholar]
  223. Clavier, Q.d.E. Epidémie de dysenterie bacillaire sur l’Armorique. Arch. Médecine Pharm. Nav. 1932, 122, 396–443. [Google Scholar]
  224. Couvy, L.; Lambert, L.; Dufour, V. Le principe lytique transmissible, dit “bacteriophage” du bacille d’YERSIN. Ann. L’institut Pasteur 1932, 48, 541–593. [Google Scholar]
  225. Davenport, G.S.; Johnsen, S.W. Case of dysentery (Flexner) treated by bacteriophage. J. Lab. Clin. Med. 1932, 18, 315–316. [Google Scholar]
  226. MacNeal, W.J. The use of bacteriophages in wound infection and in bacteremias. Am. J. Med. Sci. 1932, 184, 805. [Google Scholar] [CrossRef]
  227. Peyre, E.; Braunberger, M. Quelques exemples de traitement par le Bactériophage. Prog. Med. 1932, 5, 198–201. [Google Scholar]
  228. Schless, R.A. Staphylococcus aureus meningitis: Treatment with specific bacteriophage. Am. J. Dis. Child. 1932, 44, 813–822. [Google Scholar] [CrossRef]
  229. Schultz, E.W. Bacteriophage as a Therapeutic Agent in Genito-Urinary Infections: Part II. Calif. West. Med. 1932, 36, 91–96. [Google Scholar]
  230. Schultz, E.W. Bacteriophage as a therapeutic agent in genito-urinary infections: Part 1. Callif. West. Med. 1932, 36, 33–37. [Google Scholar]
  231. Asheshov, I. The treatment of cholera with bacteriaphage. Indian Med. Gaz. 1931, 66, 179. [Google Scholar]
  232. Barthélemy, M.; Roque, M. Infections chirurgicales traitées et guéries par le bactériophage. Bull. Mémoires Société Natl. Chir. 1931, 67, 437–439. [Google Scholar]
  233. Brisset, M. Essais de thérapeutiques et de prophylaxie avec les bactériophages locaux. Bull. Mémoires Société Natl. Chir. 1931, 58, 1310–1316. [Google Scholar]
  234. Caussade, G.F. Broncho-pneumonie traitée avec succès par le bactériophage. Disparition d’extrasystoles depuis 4 ans. Bull. Général Thérapeutique 1931, 182, 206–207. [Google Scholar]
  235. Cowie, D.M.; Hicks, W.C. Observations on the bacteriophage III. The treatment of colon bacillus infections of the urinary tract by means of subcutaneous and intravesicle of bacteriophage filtrates. Detailed case reports. Methods for preparation of filtrates. J. Lab. Clin. Med. 1931, 17, 681–730. [Google Scholar]
  236. Jusseaume, G.E.J. De L’emploi du Bactériophage de d’Hérelle Comme Traitement des Otites Moyennes Suppurée. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1931. [Google Scholar]
  237. Kahn, B.L. Bacteriophage therapy of pyodermia: Report of twenty cases. Arch. Derm. Syphilol. 1931, 24, 218–227. [Google Scholar] [CrossRef]
  238. Laroyenne; Jarricot. Sur une observation de psoïtis au cours d’une ostéomyélite vertébrale. Lyon Méd. 1931, 147, 418–419. [Google Scholar]
  239. Miraillié, C. Sur un cas d’arthrite gonococcique des deux genoux guéri par deux injections locales de bactériophage antistaphylococcique. Bull. Mémoires Société Natl. Chir. 1931, 57, 871–872. [Google Scholar]
  240. Moure, P. Le traitement des furoncles, des anthrax et des hydrosadénites par les injections du mélange bactériophage-antivirus. Bull. Mémoires Société Natl. Chir. 1931, 57, 657–661. [Google Scholar]
  241. Sassier, P. Guérison rapide d’une ostéomyélite grave par la phagothérapie. Rev. Stomatol. 1931, 33, 432–438. [Google Scholar]
  242. Sauvé, L. Enorme anthrax de la nuque traité par le bactériophage. Bull. Mémoires Société Natl. Chir. 1931, 57, 540. [Google Scholar]
  243. Stout, B.F. Septic cavernous sinus thrombosis; report of 2 cases with recovery of 1 following bacteriophage therapy. J. Lab. Clin. Med. 1931, 3, 28–39. [Google Scholar]
  244. Wiart, P.; Mirallié, C. Arthrite suppurée du genou guérie sans arthrotomie et avec un résultat fonctionnel excellent à la suite d’injections de bactériophage. Bull. Mémoires Société Natl. Chir. 1931, 5, 234–240. [Google Scholar]
  245. Basset, J.J.A. Essai de bactériophagie dans la chancrelle. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1930. [Google Scholar]
  246. Fischer, E. Contribution à L’étude du Traitement des Dermatoses Staphylococciques par le Bactériophage de d’Hérelle en Applications Locales. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1930. [Google Scholar]
  247. Gugelot, N.F.E.C. Le Bactériophage Dans la Thérapeutique des Affections Typhoïdes. Ph.D. Thesis, Université de Lille, Faculté de Médecine, Lille, France, 1930. [Google Scholar]
  248. Michon, L. Le traitement des infections urinaires à colibacilles par le bactériophage. Paris. Méd. 1930, 37, 356–359. [Google Scholar]
  249. Ricard, A.D.; Mourgues, D. Traitement de certaines inflammations et suppurations par le bactériophage. Lyon Chir. 1930, 27, 249–253. [Google Scholar]
  250. Sauvé, L. Un cas de septicémie grave à colibacilles guérie par une injection intraveineuse de bactériophage adapté (autobactériophage). Bull. Mémoires Société Natl. Chir. 1930, 56, 485. [Google Scholar]
  251. Bizard, L. Un cas de furonculose avec anthrax datant de plus de six ans, guéri par le bactériophage de d’Hérelle. J. Méde. Paris 1929, 27, 569che. [Google Scholar]
  252. Compton, A. Antidysentery bacteriophage in the treatment of bacillary dysentery. A record of sixty-six cases treated, with inferences. Lancet 1929, 214, 273–275. [Google Scholar] [CrossRef]
  253. Davioud, J. Septico-pyohemie a staphylocoque doré par le bactériophage intraveineux. Bull. Mémoires Société Natl. Chir. 1929, 33, 1413. [Google Scholar]
  254. Larkum, N.W. Bacteriophage treatment of staphylococcus infections. J. Infect. Dis. 1929, 45, 34–41. [Google Scholar] [CrossRef]
  255. Le Blaye, R. Un cas de rhinite purulente rebelle, guérie rapidement par la phagothérapie, (Soc. de Médecine de la Vienne, 8-4-29). Concours Med 1929, 20, 3181. [Google Scholar]
  256. Pitsch, G. Du rôle de la mastication dans la pyorhée alvéolo-dentaire. Le traitement de cette maladie par le bactériophage. Bul. Acad. Nat. Méd. 1929, 101, 905–907. [Google Scholar]
  257. Raiga, A. Trois cas de phlegmons d’origine dentaire guéris par le bactériophage de d’Herelle. Bull. Mémoires Société Natl. Chir. 1929, 55, 575–587. [Google Scholar]
  258. Rice, T.B. The use of bacteriophages filtrates in the treatment of suppurative conditions (report of 300 cases). Am. J. Med. Sci. 1930, 179, 345–360. [Google Scholar] [CrossRef]
  259. Sauvé, L. Le bactériophage. Bull. Mémoires Société Natl. Chir. 1929, 55, 1251–1263. [Google Scholar]
  260. Caldwell, J.A. Bacteriophagy in urinary infections following the administration of the bacteriophage therapeutically. Arch. Intern. Med. 1928, 41, 18. [Google Scholar] [CrossRef]
  261. Grenet, H.; Isaac-Georges, P. Quelques essais thérapeutiques à l’aide du bactériophage de d’Hérelle. Presse Méd. 1928, 69, 1089–1092. [Google Scholar]
  262. Rice, T.B.; Harvey, V.K. The therapeutic use of bacteriophage in suppurative conditions. Report of fifty cases. J. Lab. Clin. Med. 1928, 14, 1–12. [Google Scholar]
  263. Malone, R.H.; Bird, W. A report on three cases of bacillary dysentery treated with bacteriophage. Indian Med. Gaz. 1927, 62, 373–375. [Google Scholar]
  264. Camus, P. Le bactériophage de d’Hérelle et ses applications en oto-rhinologie. Arch. Int. Laryngol. Otol. Rhinol. Broncho-Oesophagoscopie 1926, 5, 938–955. [Google Scholar]
  265. Hauduroy, P.; Camus, J.; Dalsace, R. Le traitement des infections à staphylocoques par le bactériophage de d’Hérelle. Presse Méd. 1926, 76, 1195–1197. [Google Scholar]
  266. Larkum, N.W. Bacteriophagy in urinary infection. Part II. Bacteriophagy in the bladder. J. Bacteriol. 1926, 12, 203–223. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  267. Dalsace, R. Le Bactériophage de d’Hérelle. Ses Applications en Thérapeutique Urinaire. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1925. [Google Scholar]
  268. d’Herelle, F. Essai de traitement de la peste bubonique par le bactériophage. Presse Méd. 1925, 33, 1393–1394. [Google Scholar]
  269. Frisch, B. Traitement de l’infection colibacillaire des voies urinaires à l’aide du bacteriophage. Presse Méd. 1925, 99, 225–226. [Google Scholar]
  270. Berg, V. Le Bactériophage et son Application dans le Traitement de Quelques Maladies Infantiles. Ph.D. Thesis, Université de Strasbourg, Faculté de Médecine, Strasbourg, France, 1924. [Google Scholar]
  271. Gougerot, H.; Peyre, E. Le bactériophage dans le traitement des affections cutanées. C. R. Seances Soc. Biol. Fil. 1924, 91, 452–453. [Google Scholar]
  272. Mourret, F. Traitement des infections à staphylocoques par le bactériophage de d’Hérelle. Ph.D. Thesis, Université de Paris, Faculté de Médecine, Paris, France, 1924. [Google Scholar]
  273. Beckerich, A.; Hauduroy, P. Le traitement des infections urinaires à colibacilles par le bactériophage de d’Hérelle. Bull. Médical 1923, 37, 273. [Google Scholar]
  274. Gratia, A.; Jaumain, D. Au sujet des réactions consécutives aux injections de principe lytique staphylococcique. C. R. Seances Soc. Biol. Fil. 1922, 86, 519–520. [Google Scholar]
  275. Hauduroy, P. Syndrome dysentériforme produit par le bacille typhique. Guérison par le bactériophage de d’Hérelle. Progrès Méd. 1923, 36, 61–62. [Google Scholar]
  276. McKinley, E.B. The bacteriophage in the treatment of infections. Arch. Intern. Med. 1923, 32, 899–910. [Google Scholar] [CrossRef]
  277. Philibert, A.; Hauduroy, P. Traitement des infections à colibacille par le bactériophage de d’Hérelle. J. Des. Prat. 1923, 7. [Google Scholar]
  278. Bastin, A. Le Phénomène de d’Hérelle Considéré dans ses Rapports Avec la Biologie Générale, la Pathogénie, la Prophylaxie, et la Thérapeutique des Infections. Ph.D. Thesis, Université de Lille, Faculté de Médecine, Lille, France, 1922. [Google Scholar]
  279. Bruynoghe, R.; Maisin, J. Essais de thérapeutique au moyen du bactériophage. C. R. Seances Soc. Biol. Fil. 1922, 85, 1120–1121. [Google Scholar]
  280. Philibert, A. Un cas de pyélonéphrite gravidique traité par le bactériophage de d’Herelle. Bull. Mémoires Société Médicale Hôpitaux Paris 1922, 46, 1151–1155. [Google Scholar]
  281. Davison, W.C. The bacteriolysant therapy of bacillary dysentery in children. Therapeutic application of bacteriolysants; d’Herelle’s phenomenom. Am. J. Dis. Child 1922, 23, 531–534. [Google Scholar] [CrossRef]
  282. Leitner, L.; Sybesma, W.; Chanishvili, N.; Goderdzishvili, M.; Chkhotua, A.; Ujmajuridze, A.; Schneider, M.P.; Sartori, A.; Mehnert, U.; Bachmann, L.M.; et al. Bacteriophages for treating urinary tract infections in patients undergoing transurethral resection of the prostate: A randomized, placebo-controlled, double-blind clinical trial. BMC Urol. 2017, 17, 90. [Google Scholar] [CrossRef] [PubMed] [Green Version]
  283. Melo, L.D.R.; Oliveira, H.; Pires, D.P.; Dabrowska, K.; Azeredo, J. Phage therapy efficacy: A review of the last 10 years of pre-clinical studies. Crit. Rev. Microbiol. 2020, 46, 78–79. [Google Scholar] [CrossRef] [PubMed]
  284. Diallo, K.; Dublanchet, A. Benefits of Combined Phage-Antibiotic Therapy for the Control of Antibiotic-Resistant Bacteria: A Literature Review. Antibiotics 2022, 11, 839. [Google Scholar] [CrossRef] [PubMed]
Antibiotics 12 00751 g001 550
Figure 1. Distribution of articles on phage therapy for the main clinical foci of infection.
Figure 1. Distribution of articles on phage therapy for the main clinical foci of infection.
Antibiotics 12 00751 g001
Table
Table 1. Main prospective randomized clinical trials, literature reviews, and prospective non-randomized clinical trials.
Table 1. Main prospective randomized clinical trials, literature reviews, and prospective non-randomized clinical trials.
YearNumber of Publications and/or Patients Clinical FocusMicroorganismMain ResultsReference
202241 reports/63 patientsVariedVariedClinical success in 55 patients[27]
202120 reports/51 patientsOsteoarticular VariedClinical success[28]
20219 reports/23 patientsOsteoarticularVariedClinical success[29]
202028 patientsUrinaryP. aeruginosaClinical failure[30]
202114 clinical trials/35 case reportsVariedVariedUnspecified[31]
202148 patientsCutaneousVariedClinical success[32]
2020277 patientsOsteoarticularVariedClinical success[33]
202013 studiesDiabetic foot infectionVariedClinical success in 11 studies
Non-significant results
in 2 studies		[34]
202013 patientsSevere infectionsS. aureusSafety demonstrated[35]
202022 patientsDigestiveE. coliClinical success[36]
202027 reportsCutaneousVariedClinical success[37]
201910 studiesVariedVariedClinical success in 5 studies;
efficacy not determined
in 5 studies		[38]
201936 patientsDigestiveE. coliSafety demonstrated[39]
201936 patientsDigestiveVariedSafety demonstrated[40]
201920 patientsCutaneousE. coli
P. aeruginosa
S. aureus		Clinical failure[41]
201927 patientsCutaneousP. aeruginosaClinical failure[42]
201912 studiesVariedVariedClinical success[43]
20198 studiesVariedVariedClinical success[44]
201929 case reports/1971 patientsVariedVariedClinical success[45]
20199 patientsENTS. aureusSafety demonstrated[46]
20196 studiesVariedVariedSafety demonstrated[47]
201830 studiesVariedE. coli
S. aureus
Klebsiella pneumoniae
Acinetobacter baumannii
P. aeruginosa		Clinical success[48]
201810 patientsENTS. aureusSafety demonstrated[49]
2018234 patientsCutaneousUnspecifiedClinical success[50]
2016No publications or patients addedVariedVariedClinical success[51]
201679 patientsDigestiveE. coliClinical failure[52]
2014No publications or patients addedVariedVariedDescription of other studies[53]
2013No publications or patients addedVariedP. aeruginosaClinical success[54]
2012No publications or patients addedWoundsVariedDescription of other studies[55]
2012157 patientsVariedVariedClinical success in 44% of patients[56]
2011No publications or patients addedVariedVariedDescription of other studies[57]
2009No publications or patients addedVariedVariedDescription of other studies[58]
200939 patientsCutaneousP. aeruginosa
S. aureus
E. coli		Clinical failure[59]
200924 patientsENTP. aeruginosaClinical success[60]
2008No publications or patients addedVariedVariedDescription of other studies[61]
200515 patientsDigestiveE. coliClinical failure[62]
2001No publications or patients addedVariedVariedDescription of other studies[63]
20001307 patientsSuppurative infectionsVariedClinical success[64]
1998557 patientsVariedP. aeruginosaClinical success[65]
198731 patientsCutaneousStaphylococcus spp.
Pseudomonas spp.		Clinical success[66]
1931636 patientsCutaneousS. aureusClinical success[67]
Table
Table 2. Case reports published since 1945.
Table 2. Case reports published since 1945.
YearNumber of PatientsClinical FocusMicroorganismAntibiotic Association Y/NMain ResultsReference
20221CutaneousMycobacterium chelonaeYClinical success[68]
20211OsteoarticularStaphylococcus epidermidisYClinical success[69]
20211OsteoarticularP. aeruginosaYClinical success[70]
20211UrinaryVariedYClinical success[71]
20211OsteoarticularP. aeruginosaYClinical success[72]
20211PulmonaryAchromobacter
xylosoxidans		YClinical success[73]
20211DigestiveEnterococcus faeciumYClinical success[74]
20211OsteoarticularS. aureusYClinical success[75]
20211PulmonaryA. baumanniiYClinical success[76]
20214PulmonaryA. baumanniiYClinical success in 2 patients;
death in 2 patients		[77]
202010VariedMainly, P. aeruginosa
S. aureus
Mycobacterium abscessus		YClinical success[78]
20201UrinaryK. pneumoniaeYClinical success[79]
20201OsteoarticularK. pneumoniaeYClinical success[80]
20201OsteoarticularS. aureusYClinical success[81]
20201CardiacS. aureus and
Cutibacterium acnes		YClinical success[82]
20203OsteoarticularS. aureusYClinical success[83]
20201PulmonaryAchromobacter spp.YClinical success[84]
20201CardiacS. aureusYClinical success[85]
20201UrinaryK. pneumoniaeYClinical success[86]
20208Cardiothoracic surgeryS. aureus
E. faecium
P. aeruginosa
K. pneumoniae
E. coli		YClinical success[87]
20191CardiacS. aureusYClinical success[88]
20193PulmonaryP. aeruginosa
Burkholderia dolosa		YClinical success[89]
20191Uro-digestive colonizationK. pneumoniaeYClinical success[90]
20191PulmonaryM. abcessusYClinical success[91]
201913VariedVariedYClinical success[92]
201915UnspecifiedVariedYUnspecified[93]
20191CardiacS. aureusYClinical success[94]
20191UrinaryK. pneumoniaeYClinical success[95]
20191PulmonaryP. aeruginosaYClinical success[96]
20191PulmonaryP. aeruginosaYClinical success[97]
20191OsteoarticularA. baumanii and K. pneumoniaeYClinical success[98]
20194OsteoarticularP. aeruginosa, S. epidermidis, S. aureus, Enterococcus faecalisYClinical success[99]
20191OsteoarticularP. aeruginosaYClinical success[100]
20188Bacteraemia, endocarditis and pulmonaryS. aureus and P. aeruginosaYClinical success[101]
20181PulmonaryP. aeruginosaYClinical success[102]
20181Vascular prosthesisP. aeruginosaYClinical success[103]
20183OsteoarticularS. aureusYClinical success[104]
20181OsteoarticularP. aeruginosaYLocal success but patient death[105]
20186Diabetic footS. aureusYClinical success[106]
20181Diabetic footS. aureusYClinical success[107]
20181PulmonaryA. xylosoxidansYClinical success[108]
20181NeurosurgicalA. baumaniiNLocal success but patient death[109]
201815VariedMainly, S. aureusYClinical success in 12 patients[110]
20189UrinaryVariedNClinical success[111]
20171BacteraemiaP. aeruginosaYClinical success[112]
20171UrinaryP. aeruginosaYClinical success[113]
201787CutaneousS. aureusNClinical success[114]
20171DigestiveA. baumaniiYClinical success[115]
20173CutaneousS. aureusNClinical success[116]
20171CutaneousS. aureusNClinical success[117]
20166Diabetic footS. aureusYClinical success[118]
20169UrinaryVariedNClinical success[119]
20151OcularS. aureusUnknownClinical success[120]
20149CutaneousS. aureus and P. aeruginosaNClinical failure[121]
20111UrinaryP. aeruginosaYClinical success[122]
20111PulmonaryS. aureusYClinical success[123]
20102OsteoarticularS. aureusYClinical success[124]
200928OcularStaphylococcus spp.NClinical success[125]
20093UrinaryE. faecalisNClinical success[126]
200937OsteoarticularMainly, S. aureusYSignificant
improvement		[127]
20071ENTS. aureusYClinical success[128]
20071PulmonaryP. aeruginosaYClinical success[129]
20061Digestive
colonization		S. aureusNClinical success[130]
20061CutaneousP. aeruginosaYClinical success[131]
20061ENTStaphylococcus hominisNClinical success[132]
20052CutaneousS. aureusYClinical success[133]
200394SepsisVariedYClinical success[134]
200296CutaneousVariedNClinical success[135]
200120VariedVariedUnknownClinical success[136]
199030CutaneousP. aeruginosaNClinical success[137]
1987550Suppurative infectionsUnspecifiedYClinical success[138]
1985273VariedMainly Staphylococcus spp.YClinical success[139]
1985114VariedVariedYClinical success[140]
1985370VariedVariedYClinical success[141]
1984150VariedVariedYClinical success[142]
1983138VariedVariedYClinical success[143]
19818CutaneousS. aureusNClinical success[144]
19797OsteoarticularVariedYClinical success[145]
19781VascularSerratia marcescensYClinical failure[146]
197125DigestiveVibrio choleraeNClinical failure[147]
19651DigestiveSalmonella panamaNClinical success[148]
196245DigestiveE. coliNProphylaxis; 1 clinical failure[149]
196010VariedP. aeruginosaYClinical success[150]
195934VariedVariedYClinical success[151]
19591NeurologicalP. aeruginosaYClinical success[152]
19581NeurologicalE. coliYClinical success[153]
19532OsteoarticularS. aureus and Streptococcus spp.NClinical success[154]
194977VariedStaphylococcus spp.NClinical success[155]
194914DigestiveUnspecifiedNClinical success[156]
19481OsteoarticularUnspecifiedNClinical success[157]
19471EndocarditisStaphylococcus spp.YClinical success[158]
194656DigestiveS. typhiNUnspecified[159]
19469VariedStaphylococcus spp.YClinical success[160]
19451EndocarditisS. aureusYClinical success[161]
19457CutaneousMainly, S. aureusNClinical success[162]
ENT: ear-nose-throat; N: no; Y: yes.
Table
Table 3. Case reports published before 1945.
Table 3. Case reports published before 1945.
YearNumber of
Patients		Clinical FocusMicroorganismMain ResultsReference
194345ThrombophlebitisS. aureusUnspecified[163]
194310NeurologicalStaphylococcus spp.Clinical success[164]
1942385BacteraemiaS. aureusUnspecified[165]
19412NeurologicalS. aureusNo significant improvement[166]
19415VariedStaphylococcus spp.Clinical success[167]
19411BacteraemiaS. aureusClinical success[168]
19419SurgicalVariedClinical success[169]
194036BacteraemiaS. aureusClinical success[170]
194012Osteoarticular and bacteraemiaS. aureusClinical success[171]
19388Breast abscessMainly Staphylococcus spp.Clinical success[172]
193719UrinaryE. coliClinical success[173]
193788GynaecologicalNeisseria gonorrhoeaeClinical success[174]
19375Varied surgicalS. aureusClinical success[175]
19373OsteoarticularS. aureusClinical success[176]
1937106Osteoarticular and bacteraemiaS. aureusUnspecified[177]
19371OsteoarticularS. aureusClinical success[178]
19372BacteraemiaS. aureusClinical success[179]
193710CutaneousUnspecifiedClinical success[180]
19361BacteraemiaS. aureusClinical success[181]
193627VariedS. aureusClinical success[182]
19364NeurologicalS. aureusClinical success[183]
193615BacteraemiaS. aureusClinical success[184]
1936100BacteraemiaS. aureusUnspecified[185]
1936Around 10CutaneousUnspecifiedClinical success[186]
19361PulmonaryE. coliClinical success[187]
19361PulmonaryPolymicrobialClinical success[188]
19351BacteraemiaS. aureusClinical success[189]
19351NeurologicalS. aureusClinical success[190]
19352EndocarditisS. aureus and Streptococcus viridansClinical success[191]
1935>100CutaneousUnspecifiedClinical success[192]
19351Cutaneous and osteoarticularUnspecifiedClinical success[193]
19351Osteoarticular and bacteraemiaStaphylococcus albus, Staphylococcus haemolyticus, Streptococcus spp.Clinical success[194]
1935UnspecifiedCutaneousUnspecifiedUnspecified[195]
19351BacteraemiaS. aureusClinical success[196]
193518Cutaneous, urinary and ophthalmologicalVariedClinical success[197]
193534UrinaryMainly, E. coliClinical success[198]
19344VariedVariedClinical success[199]
193414UrinaryColon bacillusClinical success[200]
19344BacteraemiaColon bacillusNo significant improvement[201]
193414DigestiveUnspecifiedClinical success[202]
19341OsteoarticularStreptococcus spp. and Staphylococcus spp.Clinical success[203]
19341BacteraemiaS. aureusClinical success[204]
19342DigestiveUnspecifiedClinical success[205]
19347CutaneousStaphylococcus spp.Clinical success[206]
19341Osteo-articularStreptococcus spp.Clinical success[207]
1934110CutaneousStaphylococcus spp.Clinical success[208]
1933100OsteoarticularMainly Staphylococcus spp.Significant improvement[209]
193322Surgical UnspecifiedUnspecified[210]
1933200CutaneousUnspecifiedUnspecified[211]
19338DigestiveSalmonella typhi and S. paratyphiClinical success[212]
19339CutaneousStaphylococcus spp.Clinical success[213]
19331ENTStaphylococcus spp.Clinical success[214]
193349Gynaecological and bacteraemiaVariedSome clinical success[215]
19331OsteoarticularStaphylococcus spp.–S. viridansClinical success[216]
19331OsteoarticularStaphylococcus spp.Clinical success[217]
19332ENTS. aureusClinical success[218]
193330SurgicalVariedClinical success[219]
19331BacteraemiaUnspecifiedClinical success[220]
193210OsteoarticularS. aureusClinical failure[221]
19324UrinaryE. coliClinical success[222]
19328DigestiveDysenteric bacillusClinical success[223]
1932173PlagueYersin’s bacillusClinical success[224]
19321DigestiveDysenteric bacillusClinical success[225]
19327Cutaneous and bacteraemiaStaphylococcus spp. and E. coliClinical success[226]
19327Cutaneous, pulmonary and urinaryVariedClinical success[227]
19321NeurologicalS. aureusClinical success[228]
19327Urinary and gynaecologicalVariedClinical success[229]
1932191UrinaryE. coliClinical failure[230]
1931266DigestiveV. choleraeClinical success[231]
19314SurgicalVariedClinical success[232]
1931UnspecifiedVariedVariedUnspecified[233]
19311PulmonaryUnspecifiedClinical success[234]
193146UrinaryMainly, E. coliClinical success[235]
193114ENTUnspecifiedClinical success[236]
193120CutaneousStaphylococcus spp.Clinical success[237]
19311DigestiveUnspecifiedClinical success[238]
19311OsteoarticularUnspecifiedClinical success[239]
1931115CutaneousStaphylococcus spp.Clinical success[240]
19311OsteoarticularS. aureusClinical success[241]
19311CutaneousUnspecifiedClinical success[242]
19312Cavernous sinus thrombophlebitisS. aureusNo significant improvement[243]
19311OsteoarticularStaphylococcus spp.Clinical success[244]
19306CutaneousDucrey’s bacillusClinical success[245]
193013CutaneousMainly, S. aureusClinical success[246]
19304DigestiveS. typhiClinical success[247]
19305UrinaryE. coliClinical success[248]
19302CutaneousUnspecifiedClinical success[249]
19301Bacteraemia/UrinaryE. coliClinical success
via intravenous route;
clinical failure via intravesical route and subcutaneous		[250]
19291CutaneousS. aureusClinical success[251]
192966DigestiveDysenteric bacillusClinical success[252]
19291BacteraemiaS. aureusClinical success[253]
1929264CutaneousS. aureusClinical success[254]
19291ENTUnspecifiedClinical success[255]
19291ENTUnspecifiedClinical success[256]
19293ENTVariedClinical success[257]
1929>300VariedVariedClinical success[258]
192976VariedS. aureus
E. coli		Clinical success[259]
192812UrinaryE. coli and P. aeruginosaClinical success[260]
192865Urinary, digestive and otherVariedClinical failure[261]
1928Around 200VariedS. aureus
S. albus
E. coli
P. aeruginosa		Clinical success[262]
19273DigestiveD. bacillusClinical success[263]
192658ENTMainly, S. aureusClinical success[264]
1926>100Cutaneous, ENT and urinaryS. aureusClinical success[265]
19264UrinaryE. coliClinical success[266]
192530UrinaryE. coli and S. aureusClinical success[267]
19254Bubonic plagueYersinia pestisClinical success[268]
19257UrinaryE. coliClinical success[269]
192411Urinary and digestiveE. coli
Salmonella spp.		Clinical success[270]
19244CutaneousS. aureusClinical success[271]
192414CutaneousS. aureusClinical success[272]
192311UrinaryE. coliClinical success[273]
19232CutaneousS. aureusClinical success[274]
19231DigestiveSalmonella spp.Clinical success[275]
19237VariedVariedClinical success[276]
19231UrinaryE. coliClinical success[277]
19227CutaneousS. aureusClinical failure[278]
19226CutaneousS. aureusClinical success[279]
19221UrinaryE. coliClinical success[280]
192212DigestiveE. coliNo significant improvement[281]
ENT: ear-nose-throat.
Disclaimer/Publisher’s Note: The statements, opinions and data contained in all publications are solely those of the individual author(s) and contributor(s) and not of MDPI and/or the editor(s). MDPI and/or the editor(s) disclaim responsibility for any injury to people or property resulting from any ideas, methods, instructions or products referred to in the content.

Share and Cite

MDPI and ACS Style

Diallo, K.; Dublanchet, A. A Century of Clinical Use of Phages: A Literature Review. Antibiotics 2023, 12, 751. https://doi.org/10.3390/antibiotics12040751

AMA Style

Diallo K, Dublanchet A. A Century of Clinical Use of Phages: A Literature Review. Antibiotics. 2023; 12(4):751. https://doi.org/10.3390/antibiotics12040751

Chicago/Turabian Style

Diallo, Kevin, and Alain Dublanchet. 2023. "A Century of Clinical Use of Phages: A Literature Review" Antibiotics 12, no. 4: 751. https://doi.org/10.3390/antibiotics12040751

Note that from the first issue of 2016, this journal uses article numbers instead of page numbers. See further details here.

Article Metrics

Back to TopTop