دورية أكاديمية
Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia.
| العنوان: | Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia. |
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| المؤلفون: | Stellfox ME; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Fernandes C; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Shields RK; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Haidar G; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Hughes Kramer K; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Dembinski E; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA., Mangalea MR; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Arya G; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Canfield GS; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Duerkop BA; Department of Immunology and Microbiology, University of Colorado School of Medicine, Aurora, Colorado, USA., Van Tyne D; Department of Medicine, Division of Infectious Diseases, University of Pittsburgh, Pittsburgh, Pennsylvania, USA. |
| المصدر: | MBio [mBio] 2024 Mar 13; Vol. 15 (3), pp. e0339623. Date of Electronic Publication: 2024 Feb 14. |
| نوع المنشور: | Journal Article |
| اللغة: | English |
| بيانات الدورية: | Publisher: American Society for Microbiology Country of Publication: United States NLM ID: 101519231 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2150-7511 (Electronic) NLM ISO Abbreviation: mBio Subsets: MEDLINE |
| أسماء مطبوعة: | Original Publication: Washington, D.C. : American Society for Microbiology |
| مواضيع طبية MeSH: | Enterococcus faecium* , Bacteriophages*/physiology , Bacteremia*/microbiology , Gram-Positive Bacterial Infections*/microbiology , Vancomycin-Resistant Enterococci*, Humans ; Anti-Bacterial Agents/therapeutic use ; Quality of Life ; Enterococcus ; Microbial Sensitivity Tests |
| مستخلص: | Enterococcus 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. Importance: Phage 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. Competing Interests: G.H. is a recipient of research grants from Allovir, Karius, and AstraZeneca. G.H. also serves on the scientific advisory boards of Karius and AstraZeneca and has received honoraria from MDOutlook. |
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| معلومات مُعتمدة: | R01 AI127472 United States AI NIAID NIH HHS; T32 AI138954 United States AI NIAID NIH HHS; K23 AI154546 United States AI NIAID NIH HHS; R21 AI151363 United States AI NIAID NIH HHS; R01 AI141479 United States AI NIAID NIH HHS; T32 AR007534 United States AR NIAMS NIH HHS; R01 AI165519 United States AI NIAID NIH HHS |
| فهرسة مساهمة: | Keywords: bacteriophage therapy; phage-neutralizing antibodies; vancomycin-resistant Enterococcus faecium |
| المشرفين على المادة: | 0 (Anti-Bacterial Agents) |
| تواريخ الأحداث: | Date Created: 20240214 Date Completed: 20240314 Latest Revision: 20240315 |
| رمز التحديث: | 20240315 |
| مُعرف محوري في PubMed: | PMC10936196 |
| DOI: | 10.1128/mbio.03396-23 |
| PMID: | 38353560 |
| قاعدة البيانات: | MEDLINE |
Full Text Finder | تدمد: | 2150-7511 |
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| DOI: | 10.1128/mbio.03396-23 |