Bacteriophage Therapy of Difficult-to-treat Infections
Condition: Bacterial Infections
MeSH terms: Infections; Communicable Diseases; Bacterial Infections
Study type: Observational

Summary: 
      A retrospective, observational analysis of the first one hundred consecutive cases of
      bacteriophage therapy of difficult-to-treat infections, facilitated by a Belgian consortium.
    

Detailed description: 
      Background: In 2008, the Queen Astrid military hospital (QAMH) re-initiated treatments with
      phages, in selective cases. The QAMH implemented a Phage Therapy Coordination Center (PTCC),
      which is an essential step in the re-introduction of safe and efficient phage therapy, in
      collaboration with several hospitals and the public health authorities.

      In 2018, Belgium implemented a pragmatic phage therapy framework that centers on the
      magistral preparation (compounding pharmacies in the US) of tailor-made phage medicines,
      which paved the way for a broader and more structured application of phages in Belgium.

      The PTCC facilitated phage therapy in about 110 difficult-to-treat infections in patients in
      Belgium, but also abroad, as the Belgian is increasingly finding appeal in other European
      countries.

      Objective: The goal of this study is to retrospectively analyse observational data on the
      first one hundred consecutive phage therapy cases of difficult-to-treat infections, which
      were facilitated by the PTCC. The knowledge gained from these cases would help physicians to
      select effective treatment protocols and to design new clinical trials.

      Study design: A de-identified database consisting of demographical, microbiological and
      clinical observational data on 100 consecutive phage applications performed between
      01/01/2008 and 31/05/22 will be retrospectively analyzed. A list of the parameters that will
      be analyzed can be found in addendum 1.

      According to the EU Regulation No 536/2014 (Clinical Trials Regulation) and its transposition
      to Belgian Law, the retrospective non-interventional study of the de-identified existing
      phage therapy database is not considered as a an experiment on the human person and does not
      require informed consent.

      The R software environment will be used to analyze the correlation between treatment
      variables, including the applied phage products (used in combination with antibiotics or
      not), clinical protocols (proposed by the PTCC, and mostly based on the experiences of the
      Eliava Institute in the Republic of Georgia), infection types, possible adverse events,
      clinical outcome (improvement or not), and microbial eradication.

      Results will be translated into practical recommendations, which will help physicians to
      select effective treatment protocols and to design new clinical trials.

      The quality control of the used phage products was performed by Sciensano (formerly known as
      the Belgian Scientific Institute for Public Health) and clinical applications were performed
      in 34 hospitals in 12 countries (Belgium, United Kingdom, Germany, France, The Netherlands,
      Switzerland, Latvia, Tunisia, Spain, Portugal, Italy and Austria), under four different
      regulatory frameworks:

        1. Standard of care with magistral phage preparations (since 2018)

        2. Article 37 (unproven interventions in clinical practice) of the Declaration of Helsinki

        3. Standard of care with unlicensed medicines (in the United Kingdom)

        4. "Autorisation Temporaire d'Utilisation" (ATU) (in France) Written informed consent for
           the clinical application of phages was obtained from the involved patients or their
           legal representatives according to local provisions. Where warranted, local ethical
           committee approval for the application of phage therapy was obtained.

      The data was obtained through the patients' treating physicians and their authorisation to
      analyse this data, and a possible scientific publication of the results of this study, will
      be obtained.

      The study is conducted at the QAMH in Brussels under the responsibility and supervision of
      Dr. Sarah Djebara of the PTCC of the QAMH.

      Addendum 1. Observational data on the 100 consecutive phage therapy cases

      Demographics*:

      Country in which the therapy was performed/ Year in which phage therapy was initiated/
      Patient gender/ Patient age

      Infection:

      Primary infection type/ Secondary infection type/ Acute or chronic infection?/ Additional
      relevant information/ Organisms/ Antibiotic resistance profile of the targeted strain(s)

      Phage product:

      Phage name(s)/ Diluent/ Concentration (pfu/ml)

      Treatment:

      Intraoperative application/ Application route 1 (Dose/Duration)/ Application route 2
      (Dose/Duration)/ Concomitant antibiotic treatment/ Ambulatory or hospitalized?

      Adverse events:

      Adverse event/Duration/Severity/Relationship to phage treatment?/Action

      Clinical outcome:

      Clinical improvement?/Microbial eradication?/Clinical comment (additional relevant
      information)

      Regulatory context

      Published case? If yes, reference

      * The demographics data are separated from the individual cases
    

Intervention name(s): Bacteriophage therapy
Intervention type(s): Biological
Intervention description(s): Difficult-to-treat bacterial infections were treated with bacteriophages (selected from a collection of 25 individual bacteriophages and 6 bacteriophage cocktails), which were shown to target the patient's infecting bacterial strain (in vitro)
Observational model: Case-Only
Time perspective: Retrospective
Sampling method: Non-Probability Sample
Study population: 
        Patients with difficult-to-treat bacterial infections for which bacteriophage therapy was
        requested by the treating physician, and considered to be feasible and potentially
        beneficial by the Phage Therapy Coordination Center (PTCC) of the Queen Astrid military
        hospital (QAMH)
      
Keywords: Bacterial infections; Bacteriophages; Antibiotic resistance; Observational study; Retrospective analysis; Difficult to treat infections