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The selection of antibiotic- and bacteriophage-resistant Pseudomonas aeruginosa is prevented by their combination

View ORCID ProfileAude A Ferran, Marlène Z. Lacroix, Ophélie Gourbeyre, Alicia Huesca, Baptiste Gaborieau, View ORCID ProfileLaurent Debarbieux, Alain Bousquet-Mélou
doi: https://doi.org/10.1101/2022.05.25.493369
Aude A Ferran
aINTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
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  • ORCID record for Aude A Ferran
Marlène Z. Lacroix
aINTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
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Ophélie Gourbeyre
aINTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
bInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Bacteriophage Bacterium Host, Paris F-75015 France
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Alicia Huesca
aINTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
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Baptiste Gaborieau
bInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Bacteriophage Bacterium Host, Paris F-75015 France
cUniversité Paris Cité, INSERM U1137, IAME, Paris 75006, France
dAPHP, Hôpital Louis Mourier, DMU ESPRIT, Service de Médecine Intensive Réanimation, Colombes, France
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Laurent Debarbieux
bInstitut Pasteur, Université Paris Cité, CNRS UMR6047, Bacteriophage Bacterium Host, Paris F-75015 France
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  • For correspondence: laurent.debarbieux@pasteur.fr alain.bousquet-melou@envt.fr
Alain Bousquet-Mélou
aINTHERES, Université de Toulouse, INRAE, ENVT, Toulouse, France
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  • For correspondence: laurent.debarbieux@pasteur.fr alain.bousquet-melou@envt.fr
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Abstract

Objectives Bacteria developing resistance compromise the efficacy of antibiotics or bacteriophages (phages). We tested the association of these two antibacterials to circumvent resistance.

Methods With the Hollow Fiber Infection Model (HFIM), we mimicked the concentration profile of ciprofloxacin in the lungs of patients treated orally for Pseudomonas aeruginosa infections and independently, mimicked a single inhaled administration of phages (one or two phages).

Results Each treatment selects for antibiotic-or phage-resistant clones in less than 30 h. By contrast, no bacteria were recovered from the HFIM at 72 h when ciprofloxacin was started 4 h post-phage administration, even when increasing the initial bacterial concentration by a 1000 fold.

Conclusion The combination of phages with antibiotics used according to clinical regimens prevents the growth of resistant clones, providing opportunities to downscale the use of multiple antibiotics.

Competing Interest Statement

The authors have declared no competing interest.

Copyright 
The copyright holder for this preprint is the author/funder, who has granted bioRxiv a license to display the preprint in perpetuity. All rights reserved. No reuse allowed without permission.
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Posted May 25, 2022.
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The selection of antibiotic- and bacteriophage-resistant Pseudomonas aeruginosa is prevented by their combination
Aude A Ferran, Marlène Z. Lacroix, Ophélie Gourbeyre, Alicia Huesca, Baptiste Gaborieau, Laurent Debarbieux, Alain Bousquet-Mélou
bioRxiv 2022.05.25.493369; doi: https://doi.org/10.1101/2022.05.25.493369
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The selection of antibiotic- and bacteriophage-resistant Pseudomonas aeruginosa is prevented by their combination
Aude A Ferran, Marlène Z. Lacroix, Ophélie Gourbeyre, Alicia Huesca, Baptiste Gaborieau, Laurent Debarbieux, Alain Bousquet-Mélou
bioRxiv 2022.05.25.493369; doi: https://doi.org/10.1101/2022.05.25.493369

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