Analysis of phage therapy failure in a patient with a Pseudomonas aeruginosa prosthetic vascular graft infection

Clinical case of a patient with a Pseudomonas aeruginosa multidrug-resistant prosthetic vascular graft infection which was treated with a cocktail of phages (PT07, 14/01 and PNM) in combination with ceftazidime-avibactam (CAZ/AVI). After the application of the phage treatment and in absence of antimicrobial therapy, a new P. aeruginosa bloodstream infection (BSI) with a septic residual limb metastasis occurred, now involving a wild-type strain being susceptible to ß-lactams and quinolones. Clinical strains were analyzed by microbiology and whole genome sequencing techniques. In relation with phage administration, the clinical isolates of P. aeruginosa before phage therapy (HE2011471) and post phage therapy (HE2105886) showed a clonal relationship but with important genomic changes which could be involved in the resistance to this therapy. Finally, phenotypic studies showed a decreased in Minimum Inhibitory Concentration (MIC) to ß-lactams and quinolones as well as an increase of the biofilm production and phage resistant mutants in the clinical isolate of P. aeruginosa post phage therapy. Importance Phage therapy is a promising new treatment against infections produced by multi-drug resistant pathogens. For that, it would be necessary to know more about the clinical response and host-phage interactions by massive sequencing techniques to improve phage therapy application. In this work, we analyzed the clinical, microbiological and molecular features of the P. aeruginosa isolates in prosthetic vascular graft infection after the phages administration failure against this infection. This knowledge could allow to develop strategies of improvement of the use of phage therapy as treatment of multiple clinical infections. ### Competing Interest Statement The authors have declared no competing interest. ### Funding Statement PI22/00323 ### 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: Medical Direction of Hospital Universitario Virgen Macarena approved the phage therapy in this patient and after signing the informed consent by the patient by use of experimental medication as compassionate use. 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 All data produced in the present work are contained in the manuscript