Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium

Taylor Morrisette; Katherine L. Lev; Gregory S. Canfield; Breck A. Duerkop; Razieh Kebriaei; Kyle C. Stamper; Dana Holger; Susan M. Lehman; Smaranda Willcox; Cesar A. Arias; Michael J. Rybak

doi:10.1128/AAC.01623-21

Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium

Taylor Morrisette, Katherine L. Lev, Gregory S. Canfield, Breck A. Duerkop, Razieh Kebriaei, Kyle C. Stamper, Dana Holger, Susan M. Lehman, Smaranda Willcox, Cesar A. Arias, Michael J. Rybak

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6 Scopus citations

Abstract

Enterococcus faecium is a significant multidrug-resistant pathogen. Bacteriophage cocktails are being proposed to complement antibiotic therapy. After a screen of 8 E. faecium strains against 4 phages, 2 phages (113 and 9184) with the broadest host ranges were chosen for further experiments. Transmission electron microscopy, wholegenome sequencing, comparative genome analyses, and time-kill analyses were performed. Daptomycin (DAP) plus the phage cocktail (113 [myophage] and 9184 [siphopage]) showed bactericidal activity in most regimens, while DAP addition prevented phage 9184 resistance against daptomycin-nonsusceptible E. faecium.

Original language	English (US)
Article number	e01623-21
Pages (from-to)	e0162321
Journal	Antimicrobial Agents and Chemotherapy
Volume	66
Issue number	1
DOIs	https://doi.org/10.1128/AAC.01623-21
State	Published - Jan 18 2022

Keywords

Bacteriophage cocktails
Bacteriophage-antibiotic combinations
Bacteriophages
Daptomycin
Enterococcus faecium
Microbial Sensitivity Tests
Daptomycin/pharmacology
Enterococcus faecium/genetics
Anti-Bacterial Agents/pharmacology
Bacteriophages/genetics

ASJC Scopus subject areas

Pharmacology (medical)
Infectious Diseases
Pharmacology

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10.1128/AAC.01623-21

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Morrisette, T., Lev, K. L., Canfield, G. S., Duerkop, B. A., Kebriaei, R., Stamper, K. C., Holger, D., Lehman, S. M., Willcox, S., Arias, C. A., & Rybak, M. J. (2022). Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium. Antimicrobial Agents and Chemotherapy, 66(1), e0162321. Article e01623-21. https://doi.org/10.1128/AAC.01623-21

Morrisette, T, Lev, KL, Canfield, GS, Duerkop, BA, Kebriaei, R, Stamper, KC, Holger, D, Lehman, SM, Willcox, S, Arias, CA & Rybak, MJ 2022, 'Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium', Antimicrobial Agents and Chemotherapy, vol. 66, no. 1, e01623-21, pp. e0162321. https://doi.org/10.1128/AAC.01623-21

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title = "Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium",

abstract = "Enterococcus faecium is a significant multidrug-resistant pathogen. Bacteriophage cocktails are being proposed to complement antibiotic therapy. After a screen of 8 E. faecium strains against 4 phages, 2 phages (113 and 9184) with the broadest host ranges were chosen for further experiments. Transmission electron microscopy, wholegenome sequencing, comparative genome analyses, and time-kill analyses were performed. Daptomycin (DAP) plus the phage cocktail (113 [myophage] and 9184 [siphopage]) showed bactericidal activity in most regimens, while DAP addition prevented phage 9184 resistance against daptomycin-nonsusceptible E. faecium.",

keywords = "Bacteriophage cocktails, Bacteriophage-antibiotic combinations, Bacteriophages, Daptomycin, Enterococcus faecium, Microbial Sensitivity Tests, Daptomycin/pharmacology, Enterococcus faecium/genetics, Anti-Bacterial Agents/pharmacology, Bacteriophages/genetics",

author = "Taylor Morrisette and Lev, {Katherine L.} and Canfield, {Gregory S.} and Duerkop, {Breck A.} and Razieh Kebriaei and Stamper, {Kyle C.} and Dana Holger and Lehman, {Susan M.} and Smaranda Willcox and Arias, {Cesar A.} and Rybak, {Michael J.}",

note = "Funding Information: This work was partially supported by NIAID R01-AI121400 (M.J.R.). B.A.D. is partially supported by NIAID R01-AI141479. C.A.A. is partially supported by NIH/NIAID grants R01-AI148342, R01-AI134637, P01-AI152999, and K24-AI121296. M.J.R. is partially supported by NIAID R01-AI121400 and R21-AI163726-01. T.M., K.L.L., G.S.C. R.K., J.C.A., K.C.S., S.W., and S.M.L. have no conflicts of interest to disclose. Publisher Copyright: {\textcopyright} 2022 American Society for Microbiology.",

year = "2022",

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doi = "10.1128/AAC.01623-21",

language = "English (US)",

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AU - Morrisette, Taylor

AU - Lev, Katherine L.

AU - Canfield, Gregory S.

AU - Duerkop, Breck A.

AU - Kebriaei, Razieh

AU - Stamper, Kyle C.

AU - Holger, Dana

AU - Lehman, Susan M.

AU - Willcox, Smaranda

AU - Arias, Cesar A.

AU - Rybak, Michael J.

N1 - Funding Information: This work was partially supported by NIAID R01-AI121400 (M.J.R.). B.A.D. is partially supported by NIAID R01-AI141479. C.A.A. is partially supported by NIH/NIAID grants R01-AI148342, R01-AI134637, P01-AI152999, and K24-AI121296. M.J.R. is partially supported by NIAID R01-AI121400 and R21-AI163726-01. T.M., K.L.L., G.S.C. R.K., J.C.A., K.C.S., S.W., and S.M.L. have no conflicts of interest to disclose. Publisher Copyright: © 2022 American Society for Microbiology.

PY - 2022/1/18

Y1 - 2022/1/18

N2 - Enterococcus faecium is a significant multidrug-resistant pathogen. Bacteriophage cocktails are being proposed to complement antibiotic therapy. After a screen of 8 E. faecium strains against 4 phages, 2 phages (113 and 9184) with the broadest host ranges were chosen for further experiments. Transmission electron microscopy, wholegenome sequencing, comparative genome analyses, and time-kill analyses were performed. Daptomycin (DAP) plus the phage cocktail (113 [myophage] and 9184 [siphopage]) showed bactericidal activity in most regimens, while DAP addition prevented phage 9184 resistance against daptomycin-nonsusceptible E. faecium.

AB - Enterococcus faecium is a significant multidrug-resistant pathogen. Bacteriophage cocktails are being proposed to complement antibiotic therapy. After a screen of 8 E. faecium strains against 4 phages, 2 phages (113 and 9184) with the broadest host ranges were chosen for further experiments. Transmission electron microscopy, wholegenome sequencing, comparative genome analyses, and time-kill analyses were performed. Daptomycin (DAP) plus the phage cocktail (113 [myophage] and 9184 [siphopage]) showed bactericidal activity in most regimens, while DAP addition prevented phage 9184 resistance against daptomycin-nonsusceptible E. faecium.

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KW - Bacteriophage-antibiotic combinations

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KW - Enterococcus faecium/genetics

KW - Anti-Bacterial Agents/pharmacology

KW - Bacteriophages/genetics

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ER -

Evaluation of Bacteriophage Cocktails Alone and in Combination with Daptomycin against Daptomycin-Nonsusceptible Enterococcus faecium

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