Retrospective, observational analysis of the first one hundred consecutive cases of personalized bacteriophage therapy of difficult-to-treat infections facilitated by a Belgian consortium

In contrast to the many reports of successful cases of personalized bacteriophage therapy, randomized controlled trials of non-personalized bacteriophage products did not bring the expected results. Here, we present the outcomes of a retrospective, observational analysis of the first 100 consecutive cases of personalized bacteriophage therapy of difficult-to-treat infections facilitated by a Belgian consortium. The most common indications were lower respiratory tract, skin & soft tissue, and bone infections, and involved combinations of 26 bacteriophages, individually selected and sometimes pre-adapted to target the causative bacterial pathogens. Clinical improvement and eradication of the targeted bacteria were reported for 77.2% and 61.3% of infections, respectively. Eradication was 70% less probable when no concomitant antibiotics were used (odds-ratio = 0.3; 95% confidence interval = 0.127–0.749). In vivo selection of bacteriophage resistance and in vitro bacteriophage-antibiotic synergy were documented in 43.8% (7/16 patients) and 90% (9/10) of evaluated patients, respectively. Bacteriophage immune neutralization was observed in 38.5% (5/13) of screened patients. (BT100 study, [ClinicalTrials.gov][1] registration: [NCT05498363][2].) ### Competing Interest Statement The authors have declared no competing interest. ### Clinical Protocols ### Funding Statement This study did not receive any funding. ### Author Declarations I confirm all relevant ethical guidelines have been followed, and any necessary IRB and/or ethics committee approvals have been obtained. Yes The details of the IRB/oversight body that provided approval or exemption for the research described are given below: The Leading Ethical Committee of the Universitair Ziekenhuis Antwerpen and the Universiteit Antwerpen gave ethical approval (ID 3644) for this work. I confirm that all necessary patient/participant consent has been obtained and the appropriate institutional forms have been archived, and that any patient/participant/sample identifiers included were not known to anyone (e.g., hospital staff, patients or participants themselves) outside the research group so cannot be used to identify individuals. Yes I understand that all clinical trials and any other prospective interventional studies must be registered with an ICMJE-approved registry, such as ClinicalTrials.gov. I confirm that any such study reported in the manuscript has been registered and the trial registration ID is provided (note: if posting a prospective study registered retrospectively, please provide a statement in the trial ID field explaining why the study was not registered in advance). Yes I have followed all appropriate research reporting guidelines, such as any relevant EQUATOR Network research reporting checklist(s) and other pertinent material, if applicable. Yes Detailed clinical protocols, results, and additional data are available in the manuscript and in Supplementary Tables 1 and 2. The protocol for the retrospective, observational study is available at: . The bacteriophage genome sequences can be retrieved in the GenBank database under the accession codes listed in [Extended Data Table 2][3]. The genome data of the bacterial isolates can be accessed via the NCBI BioProject PRJNA975428. The authors declare that all other data supporting the findings of this study are available within the article. [1]: http://ClinicalTrials.gov [2]: /lookup/external-ref?link_type=CLINTRIALGOV&access_num=NCT05498363&atom=%2Fmedrxiv%2Fearly%2F2023%2F08%2F28%2F2023.08.28.23294728.atom [3]: #T2