Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia
ABSTRACTEnterococcus faecium is a member of the human gastrointestinal (GI) 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 resistanc...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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American Society for Microbiology
2024-03-01
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| Series: | mBio |
| Subjects: | |
| Online Access: | https://journals.asm.org/doi/10.1128/mbio.03396-23 |
| _version_ | 1797263275247796224 |
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| author | Madison E. Stellfox Carolyn Fernandes Ryan K. Shields Ghady Haidar Kailey Hughes Kramer Emily Dembinski Mihnea R. Mangalea Garima Arya Gregory S. Canfield Breck A. Duerkop Daria Van Tyne |
| author_facet | Madison E. Stellfox Carolyn Fernandes Ryan K. Shields Ghady Haidar Kailey Hughes Kramer Emily Dembinski Mihnea R. Mangalea Garima Arya Gregory S. Canfield Breck A. Duerkop Daria Van Tyne |
| author_sort | Madison E. Stellfox |
| collection | DOAJ |
| description | ABSTRACTEnterococcus faecium is a member of the human gastrointestinal (GI) 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, which 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 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient’s gastrointestinal (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. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided 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.IMPORTANCEPhage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit. |
| first_indexed | 2024-04-25T00:10:25Z |
| format | Article |
| id | doaj.art-9d1898c6b1d8494491170f7dce759c49 |
| institution | Directory Open Access Journal |
| issn | 2150-7511 |
| language | English |
| last_indexed | 2024-04-25T00:10:25Z |
| publishDate | 2024-03-01 |
| publisher | American Society for Microbiology |
| record_format | Article |
| series | mBio |
| spelling | doaj.art-9d1898c6b1d8494491170f7dce759c492024-03-13T14:01:04ZengAmerican Society for MicrobiologymBio2150-75112024-03-0115310.1128/mbio.03396-23Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremiaMadison E. Stellfox0Carolyn Fernandes1Ryan K. Shields2Ghady Haidar3Kailey Hughes Kramer4Emily Dembinski5Mihnea R. Mangalea6Garima Arya7Gregory S. Canfield8Breck A. Duerkop9Daria Van Tyne10Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USADepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USADepartment of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USAABSTRACTEnterococcus faecium is a member of the human gastrointestinal (GI) 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, which 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 2 years and that invasive isolates likely emerged from a large E. faecium population in the patient’s gastrointestinal (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. In vitro analysis showed that antibiotic and phage combination therapy improved bacterial growth suppression compared to therapy with either alone. Eventual E. faecium BSI recurrence was not associated with the development of antibiotic or phage resistance in post-treatment isolates. However, an anti-phage-neutralizing antibody response occurred that coincided 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.IMPORTANCEPhage therapy is an emerging therapeutic approach for treating bacterial infections that do not respond to traditional antibiotics. The addition of phage therapy to systemic antibiotics to treat a patient with recurrent E. faecium infections that were non-responsive to antibiotics alone resulted in fewer hospitalizations and improved the patient's quality of life. Combination phage and antibiotic therapy reduced E. faecium and VRE abundance in the patient's stool. Eventually, an anti-phage antibody response emerged that was able to neutralize phage activity, which may have limited clinical efficacy. This study demonstrates the potential of phages as an additional option in the antimicrobial toolbox for treating invasive enterococcal infections and highlights the need for further investigation to ensure phage therapy can be deployed for maximum clinical benefit.https://journals.asm.org/doi/10.1128/mbio.03396-23vancomycin-resistant Enterococcus faeciumbacteriophage therapyphage-neutralizing antibodies |
| spellingShingle | Madison E. Stellfox Carolyn Fernandes Ryan K. Shields Ghady Haidar Kailey Hughes Kramer Emily Dembinski Mihnea R. Mangalea Garima Arya Gregory S. Canfield Breck A. Duerkop Daria Van Tyne Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia mBio vancomycin-resistant Enterococcus faecium bacteriophage therapy phage-neutralizing antibodies |
| title | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia |
| title_full | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia |
| title_fullStr | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia |
| title_full_unstemmed | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia |
| title_short | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia |
| title_sort | bacteriophage and antibiotic combination therapy for recurrent enterococcus faecium bacteremia |
| topic | vancomycin-resistant Enterococcus faecium bacteriophage therapy phage-neutralizing antibodies |
| url | https://journals.asm.org/doi/10.1128/mbio.03396-23 |
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