Bacteriophage and antibiotic combination therapy for recurrent
            <i>Enterococcus faecium</i>
            bacteremia

Stellfox, Madison E.; Fernandes, Carolyn; Shields, Ryan K.; Haidar, Ghady; Hughes Kramer, Kailey; Dembinski, Emily; Mangalea, Mihnea R.; Arya, Garima; Canfield, Gregory S.; Duerkop, Breck A.; Van Tyne, Daria

doi:10.1128/mbio.03396-23

Cited by 6 publications

(2 citation statements)

References 16 publications

(14 reference statements)

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“…Synergistic effects between phages and β-lactam/daptomycin were already observed in vitro or ex vivo for some E. faecium isolates ( 22 – 24 ). Clinically, a concurrent treatment with traditional antibiotics (that alone had failed to eradicate recurrent E. faecium bacteremia) with phages temporarily suppressed the episodic bloodstream infections and lowered the intestinal E. faecium load of a patient ( 73 ). These data underline the clinical relevance in pursuing in vitro and pre-clinical studies assessing the possibilities offered by phage and antibiotic combinations to fight enterococci infections ( 73 ).…”

Section: Resultsmentioning

confidence: 99%

“…Clinically, a concurrent treatment with traditional antibiotics (that alone had failed to eradicate recurrent E. faecium bacteremia) with phages temporarily suppressed the episodic bloodstream infections and lowered the intestinal E. faecium load of a patient ( 73 ). These data underline the clinical relevance in pursuing in vitro and pre-clinical studies assessing the possibilities offered by phage and antibiotic combinations to fight enterococci infections ( 73 ). We tested whether the combination of phages and teicoplanin reduced bacterial overgrowth.…”

Section: Resultsmentioning

confidence: 99%

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The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method

Lossouarn,

Beurrier,

Bouteau

et al. 2024

Antimicrob Agents Chemother

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Phage therapy has (re)emerged as a serious possibility for combating multidrug-resistant bacterial infections, including those caused by vancomycin-resistant Enterococcus faecium strains. These opportunistic pathogens belong to a specific clonal complex 17, against which relatively few phages have been screened. We isolated a collection of 21 virulent phages growing on these vancomycin-resistant isolates. Each of these phages harbored a typical narrow plaquing host range, lysing at most 5 strains and covering together 10 strains of our panel of 14 clinical isolates. To enlarge the host spectrum of our phages, the Appelmans protocol was used. We mixed four out of our most complementary phages in a cocktail that we iteratively grew on eight naive strains from our panel, of which six were initially refractory to at least three of the combined phages. Fifteen successive passages permitted to significantly improve the lytic activity of the cocktail, from which phages with extended host ranges within the E. faecium species could be isolated. A single evolved phage able to kill up to 10 of the 14 initial E. faecium strains was obtained, and it barely infected nearby species. All evolved phages had acquired point mutations or a recombination event in the tail fiber genetic region, suggesting these genes might have driven phage evolution by contributing to their extended host spectra.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method

Lossouarn,

Beurrier,

Bouteau

et al. 2024

Antimicrob Agents Chemother

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Conjugated therapeutic proteins as a treatment for bacteria which trigger cancer development

Halawa,

Newman,

Aderibigbe

et al. 2024

iScience

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Translational research priorities for bacteriophage therapeutics

Schooley

2024

Essays in Biochemistry

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The growing threat of antimicrobial resistant (AMR) bacterial pathogens coupled with the relative dearth of promising novel antibiotics requires the discovery and development additional medical interventions. Over the past decade bacteriophages have emerged one of the most promising new tools to combat AMR pathogens. Anecdotal clinical experiences under so-called ‘compassionate use’ regulatory pathways as well as a limited number of clinical trials have provided ample evidence of safety and early evidence of efficacy. For phages to reach their full potential it is critical that rigorous clinical trials be conducted that define their optimal use and that enable regulatory authorities to support the commercialization required to afford global access. The clinical development of phage therapeutics requires the design and execution of clinical trials that take full advantage of lessons learned from a century of antibiotic development and that use clinical investigation as a platform in which aspects of phage biology that are critical to therapeutics are more clearly elucidated. Translational research that elucidates phage biology in the context of clinical trials will promote highly relevant hypothesis-driven work in basic science laboratories and will greatly accelerate the development of the field of phage therapeutics.

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Bacteriophage and antibiotic combination therapy for recurrent Enterococcus faecium bacteremia

Cited by 6 publications

References 16 publications

The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method

The virtue of training: extending phage host spectra against vancomycin-resistant Enterococcus faecium strains using the Appelmans method

Conjugated therapeutic proteins as a treatment for bacteria which trigger cancer development

Translational research priorities for bacteriophage therapeutics

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