Clinical Indications and Compassionate Use of Phage Therapy: Personal Experience and Literature Review with a Focus on Osteoarticular Infections

Abstract

The history of phage therapy started with its first clinical application in 1919 and continues its development to this day. Phages continue to lack any market approval in Western medicine as a recognized drug, but are increasingly used as an experimental therapy for the compassionate treatment of patients experiencing antibiotic failure. The few formal experimental phage clinical trials that have been completed to date have produced inconclusive results on the efficacy of phage therapy, which contradicts the many successful treatment outcomes observed in historical accounts and recent individual case reports. It would therefore be wise to identify why such a discordance exists between trials and compassionate use in order to better develop future phage treatment and clinical applications. The multitude of observations reported over the years in the literature constitutes an invaluable experience, and we add to this by presenting a number of cases of patients treated compassionately with phages throughout the past decade with a focus on osteoarticular infections. Additionally, an abundance of scientific literature into phage-related areas is transforming our knowledge base, creating a greater understanding that should be applied for future clinical applications. Due to the increasing number of treatment failures anticipatedfrom the perspective of a possible post-antibiotic era, we believe that the introduction of bacteriophages into the therapeutic arsenal seems a scientifically sound and eminently practicable consideration today as a substitute or adjuvant to antibiotic therapy.

Bacteriophage activity against and characterisation of avian pathogenic Escherichia coli isolated from colibacillosis cases in Uganda

“…This is in agreement with other studies that demonstrated that phages usually have a limited host range [35,58]. Apart from situations of compassionate use where a single bacterial strain associated with an infection is targeted, having a relatively broad host range is one of the desirable properties for selection of candidates for phage therapy [59,60]. The two phages, UPEC04 and UPEC10, which had a combined lytic activity against 14 APEC isolates, are better candidates for formulation of cocktails for therapeutic intervention compared to the others.…”

Bacteriophage activity against and characterisation of avian pathogenic Escherichia coli isolated from colibacillosis cases in Uganda

“…This is in agreement with other studies that demonstrated that phages usually have a limited host range [35,58]. Apart from situations of compassionate use where a single bacterial strain associated with an infection is targeted, having a relatively broad host range is one of the desirable properties for selection of candidates for phage therapy [59,60]. The two phages, UPEC04 and UPEC10, which had a combined lytic activity against 14 APEC isolates, are better candidates for formulation of cocktails for therapeutic intervention compared to the others.…”

Preclinical Development of a Bacteriophage Cocktail for Treating Multidrug Resistant Pseudomonas aeruginosa Infections

“…A nasal spray would expose the phages to a different environment with pH levels around 5.5-6.5 dependent on the nasal mucosa [4]. Results from this study show phages were stable at a wide pH range (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection

“…Otherwise, the median CRP values in the patient groups on days 3 ± 1 and 7 ± 1 after surgery would be the same, and would reflect the usual acute phase response of the patient’s body to surgery. Such results can be explained by the possible phage-antibiotic synergy, which previously was described as a promising therapeutic effect in several in vitro experiments, in vivo animal model studies, and in a few clinical studies [ 31 , 54 , 55 , 56 ].…”

Bacteriophage activity against and characterisation of avian pathogenic Escherichia coli isolated from colibacillosis cases in Uganda

“…This is in agreement with other studies that demonstrated that phages usually have a limited host range [35,58]. Apart from situations of compassionate use where a single bacterial strain associated with an infection is targeted, having a relatively broad host range is one of the desirable properties for selection of candidates for phage therapy [59,60]. The two phages, UPEC04 and UPEC10, which had a combined lytic activity against 14 APEC isolates, are better candidates for formulation of cocktails for therapeutic intervention compared to the others.…”

Preclinical Development of a Bacteriophage Cocktail for Treating Multidrug Resistant Pseudomonas aeruginosa Infections

“…A nasal spray would expose the phages to a different environment with pH levels around 5.5-6.5 dependent on the nasal mucosa [4]. Results from this study show phages were stable at a wide pH range (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection

“…Otherwise, the median CRP values in the patient groups on days 3 ± 1 and 7 ± 1 after surgery would be the same, and would reflect the usual acute phase response of the patient’s body to surgery. Such results can be explained by the possible phage-antibiotic synergy, which previously was described as a promising therapeutic effect in several in vitro experiments, in vivo animal model studies, and in a few clinical studies [ 31 , 54 , 55 , 56 ].…”

Bacteriophage activity against and characterisation of avian pathogenic Escherichia coli isolated from colibacillosis cases in Uganda

“…This is in agreement with other studies that demonstrated that phages usually have a limited host range [35,58]. Apart from situations of compassionate use where a single bacterial strain associated with an infection is targeted, having a relatively broad host range is one of the desirable properties for selection of candidates for phage therapy [59,60]. The two phages, UPEC04 and UPEC10, which had a combined lytic activity against 14 APEC isolates, are better candidates for formulation of cocktails for therapeutic intervention compared to the others.…”

Preclinical Development of a Bacteriophage Cocktail for Treating Multidrug Resistant Pseudomonas aeruginosa Infections

“…A nasal spray would expose the phages to a different environment with pH levels around 5.5-6.5 dependent on the nasal mucosa [4]. Results from this study show phages were stable at a wide pH range (3)(4)(5)(6)(7)(8)(9)(10)(11).…”

Short-Term Outcomes of Phage-Antibiotic Combination Treatment in Adult Patients with Periprosthetic Hip Joint Infection

“…Otherwise, the median CRP values in the patient groups on days 3 ± 1 and 7 ± 1 after surgery would be the same, and would reflect the usual acute phase response of the patient’s body to surgery. Such results can be explained by the possible phage-antibiotic synergy, which previously was described as a promising therapeutic effect in several in vitro experiments, in vivo animal model studies, and in a few clinical studies [ 31 , 54 , 55 , 56 ].…”