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#bacteremia

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Vivek Mutalik

#Bacteriophage and #antibiotic combination #therapy for recurrent #Enterococcus faecium #bacteremia | medRxiv

medrxiv.org/content/10.1101/20

medRxivBacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremiaEnterococcus faecium is a member of the human gastrointestinal (GI) tract microbiota but can also cause invasive infections, especially in immunocompromised hosts. Enterococci display intrinsic resistance to many antibiotics, and most clinical E. faecium isolates have acquired vancomycin resistance, leaving clinicians with a limited repertoire of effective antibiotics. As such, vancomycin-resistant E. faecium (VREfm) has become an increasingly difficult to treat nosocomial pathogen that is often associated with treatment failure and recurrent infections. We followed a patient with recurrent E. faecium bloodstream infections (BSIs) of increasing severity that ultimately became unresponsive to antibiotic combination therapy over the course of 7 years. Whole genome sequencing (WGS) showed that the patient was colonized with closely related E. faecium strains for at least two years, and that invasive isolates likely emerged from a large E. faecium population in the patient's GI tract. The addition of bacteriophage (phage) therapy to the patient's antimicrobial regimen was associated with several months of clinical improvement and reduced intestinal burden of VRE and E. faecium . Eventual recurrence of E. faecium BSI was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage neutralizing antibody response occurred simultaneously with an increased relative abundance of VRE in the GI tract, both of which may have contributed to clinical failure. Taken together, these findings highlight the potential utility and limitations of phage therapy to treat antibiotic-resistant enterococcal infections. ### Competing Interest Statement GH is a recipient of research grants from Allovir, Karius, and AstraZeneca. GH also serves on the scientific advisory boards of Karius and AstraZeneca and has received honoraria from MDOutlook. ### Clinical Trial eIND #27183 ### Funding Statement Research reported in this publication was supported by the National Institute of Allergy and Infectious Diseases of the National Institutes of Health under Award Number R01AI165519 (to DVT) and R21AI151363 (to RKS). This work was also supported by grants R01AI141479 (BAD), T32AR007534 (MRM), and K23AI154546 (GH) from the NIH. The content is solely the responsibility of the authors and does not represent the official views of the National Institutes of Health. ### 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: FDA emergency investigational new drug approval for administration of phages was obtained (eIND #27183), and the Institutional Review Board at the University of Pittsburgh also approved the study (Protocol #EA20120145). The patient provided informed consent to participate in the study. 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 and uploaded the relevant EQUATOR Network research reporting checklist(s) and other pertinent material as supplementary files, if applicable. Yes Genome sequencing data for all isolates was submitted to NCBI under BioProject PRJNA901969, with accession numbers listed in Supplemental Table 1. Other data presented are available upon reasonable request to the authors.
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