Phage-antibiotic combinations in various treatment modalities to manage MRSA infections

Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are mu...

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Main Authors: Archana Loganathan, Bulent Bozdogan, Prasanth Manohar, Ramesh Nachimuthu
Format: Article
Language:English
Published: Frontiers Media S.A. 2024-04-01
Series:Frontiers in Pharmacology
Subjects:
Online Access:https://www.frontiersin.org/articles/10.3389/fphar.2024.1356179/full
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author Archana Loganathan
Bulent Bozdogan
Prasanth Manohar
Ramesh Nachimuthu
author_facet Archana Loganathan
Bulent Bozdogan
Prasanth Manohar
Ramesh Nachimuthu
author_sort Archana Loganathan
collection DOAJ
description Introduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature.Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages.Results: When the media was supplemented with sub-inhibitory concentrations of 0.25 μg/mL and 1 μg/mL, the size of the plaque increased from 0.5 ± 0.1 mm (in the control group with only the phage) to 4 ± 0.2 mm, 1.6 ± 0.1 mm, and 1.6 ± 0.4 mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups.Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.
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spelling doaj.art-0ac0417b64c441f98180ff8462a6c7d52024-04-09T04:51:40ZengFrontiers Media S.A.Frontiers in Pharmacology1663-98122024-04-011510.3389/fphar.2024.13561791356179Phage-antibiotic combinations in various treatment modalities to manage MRSA infectionsArchana Loganathan0Bulent Bozdogan1Prasanth Manohar2Ramesh Nachimuthu3School of Bioscience and Technology, Vellore Institute of Technology (VIT), Vellore, IndiaMedical Microbiology Department, Adnan Menderes University, Aydin, TürkiyeSchool of Bioscience and Technology, Vellore Institute of Technology (VIT), Vellore, IndiaSchool of Bioscience and Technology, Vellore Institute of Technology (VIT), Vellore, IndiaIntroduction: The emergence of antibiotic resistance is a significant challenge in the treatment of bacterial infections, particularly in patients in the intensive care unit (ICU). Phage-antibiotic combination therapy is now being utilized as a preferred therapeutic option for infections that are multi-drug resistant in nature.Methods: In this study, we examined the combined impact of the staph phage vB_Sau_S90 and four antibiotics on methicillin-resistant Staphylococcus aureus (MRSA). We conducted experiments on three different treatment sequences: a) administering phages before antibiotics, b) administering phages and antibiotics simultaneously, and c) administering antibiotics before phages.Results: When the media was supplemented with sub-inhibitory concentrations of 0.25 μg/mL and 1 μg/mL, the size of the plaque increased from 0.5 ± 0.1 mm (in the control group with only the phage) to 4 ± 0.2 mm, 1.6 ± 0.1 mm, and 1.6 ± 0.4 mm when fosfomycin, ciprofloxacin, and oxacillin were added, respectively. The checkerboard analysis revealed a synergistic effect between the phages and antibiotics investigated, as indicated by a FIC value of less than 0.5. The combination treatment of phages and antibiotics demonstrated universal efficacy across all treatments. Nevertheless, the optimal effectiveness was demonstrated when the antibiotics were delivered subsequent to the phages. Utilizing the Galleria mellonella model, in vivo experiments showed that the combination of phage-oxacillin effectively eliminated biofilm-infected larvae, resulting in a survival rate of up to 80% in the treated groups.Discussion: Our findings highlight the advantages of using a combination of phage and antibiotic over using phages alone in the treatment of MRSA infections.https://www.frontiersin.org/articles/10.3389/fphar.2024.1356179/fullphage-antibiotic synergycombination therapyStaphylococcus aureusGalleria mellonellatreatment strategy
spellingShingle Archana Loganathan
Bulent Bozdogan
Prasanth Manohar
Ramesh Nachimuthu
Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
Frontiers in Pharmacology
phage-antibiotic synergy
combination therapy
Staphylococcus aureus
Galleria mellonella
treatment strategy
title Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
title_full Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
title_fullStr Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
title_full_unstemmed Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
title_short Phage-antibiotic combinations in various treatment modalities to manage MRSA infections
title_sort phage antibiotic combinations in various treatment modalities to manage mrsa infections
topic phage-antibiotic synergy
combination therapy
Staphylococcus aureus
Galleria mellonella
treatment strategy
url https://www.frontiersin.org/articles/10.3389/fphar.2024.1356179/full
work_keys_str_mv AT archanaloganathan phageantibioticcombinationsinvarioustreatmentmodalitiestomanagemrsainfections
AT bulentbozdogan phageantibioticcombinationsinvarioustreatmentmodalitiestomanagemrsainfections
AT prasanthmanohar phageantibioticcombinationsinvarioustreatmentmodalitiestomanagemrsainfections
AT rameshnachimuthu phageantibioticcombinationsinvarioustreatmentmodalitiestomanagemrsainfections