Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model

Background: Prosthetic joint infections (PJI) are difficult to treat complications of joint arthroplasty. Debridement with implant retention is a common treatment strategy and frequently involves the use of pulsed lavage (PL). However, PL effects on biofilms and antibiotic activity have been scarcel...

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Main Authors: Hervé Poilvache, Albert Ruiz-Sorribas, George Sakoulas, Hector Rodriguez-Villalobos, Olivier Cornu, Françoise Van Bambeke
Format: Article
Language:English
Published: Frontiers Media S.A. 2020-09-01
Series:Frontiers in Medicine
Subjects:
Online Access:https://www.frontiersin.org/article/10.3389/fmed.2020.00527/full
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author Hervé Poilvache
Hervé Poilvache
Hervé Poilvache
Albert Ruiz-Sorribas
George Sakoulas
Hector Rodriguez-Villalobos
Olivier Cornu
Olivier Cornu
Françoise Van Bambeke
author_facet Hervé Poilvache
Hervé Poilvache
Hervé Poilvache
Albert Ruiz-Sorribas
George Sakoulas
Hector Rodriguez-Villalobos
Olivier Cornu
Olivier Cornu
Françoise Van Bambeke
author_sort Hervé Poilvache
collection DOAJ
description Background: Prosthetic joint infections (PJI) are difficult to treat complications of joint arthroplasty. Debridement with implant retention is a common treatment strategy and frequently involves the use of pulsed lavage (PL). However, PL effects on biofilms and antibiotic activity have been scarcely studied in-vitro. We report the effects of PL, vancomycin or flucloxacillin used independently or in combination against Staphylococcus aureus biofilms.Methods: Biofilms of 3 methicillin-susceptible (MSSA) and of 3 methicillin-resistant (MRSA) S. aureus were grown on Ti6Al4V coupons in TGN (TSB + 1%glucose + 2%NaCl). After 24 h, PL was applied to half of the samples (50 mL saline from 5 cm). Samples were either reincubated for 24 h in TGN or TGN + flucloxacillin or vancomycin. Analyses included CFUs counts, biomass assays or fluorescence microscopy.Results: PL transiently reduced bacterial counts by 3–4 Log10 CFU/coupon, but bacterial regrowth to baseline levels was seen after 24 h. At 20 mg/L, flucloxacillin reduced both the CFU counts (3 Log10 CFU/coupon) and biomass (−70%) in one MSSA only, while vancomycin had no effects against MRSA. PL combined with a 24 h reincubation with vancomycin or flucloxacillin at 20 mg/L was synergistic (−5 to 6.5 Log10 CFU/coupon; 81–100% biomass reduction). Fluorescence microscopy confirmed that PL removed most of the biofilm and that subsequent antibiotic treatment partially killed bacteria.Conclusions: While PL only transiently reduces the bacterial load and antibiotics at clinically relevant concentrations show no or limited activity on biofilms, their combination is synergistic against MRSA and MSSA biofilms. These results highlight the need for thorough PL before antibiotic administration in PJI.
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spelling doaj.art-33600d1ea34249358fce2dada269cd652022-12-22T00:08:33ZengFrontiers Media S.A.Frontiers in Medicine2296-858X2020-09-01710.3389/fmed.2020.00527527221Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro ModelHervé Poilvache0Hervé Poilvache1Hervé Poilvache2Albert Ruiz-Sorribas3George Sakoulas4Hector Rodriguez-Villalobos5Olivier Cornu6Olivier Cornu7Françoise Van Bambeke8Laboratoire de Neuro-Musculo-Squelettique, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, BelgiumLaboratoire de Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, BelgiumOrthopaedic Surgery Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumLaboratoire de Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, BelgiumSchool of Medicine, University of California, San Diego, San Diego, CA, United StatesClinical Microbiology Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumLaboratoire de Neuro-Musculo-Squelettique, Institut de Recherche Expérimentale et Clinique, Université Catholique de Louvain, Brussels, BelgiumOrthopaedic Surgery Department, Cliniques Universitaires Saint-Luc, Brussels, BelgiumLaboratoire de Pharmacologie Cellulaire et Moléculaire, Louvain Drug Research Institute, Université Catholique de Louvain, Brussels, BelgiumBackground: Prosthetic joint infections (PJI) are difficult to treat complications of joint arthroplasty. Debridement with implant retention is a common treatment strategy and frequently involves the use of pulsed lavage (PL). However, PL effects on biofilms and antibiotic activity have been scarcely studied in-vitro. We report the effects of PL, vancomycin or flucloxacillin used independently or in combination against Staphylococcus aureus biofilms.Methods: Biofilms of 3 methicillin-susceptible (MSSA) and of 3 methicillin-resistant (MRSA) S. aureus were grown on Ti6Al4V coupons in TGN (TSB + 1%glucose + 2%NaCl). After 24 h, PL was applied to half of the samples (50 mL saline from 5 cm). Samples were either reincubated for 24 h in TGN or TGN + flucloxacillin or vancomycin. Analyses included CFUs counts, biomass assays or fluorescence microscopy.Results: PL transiently reduced bacterial counts by 3–4 Log10 CFU/coupon, but bacterial regrowth to baseline levels was seen after 24 h. At 20 mg/L, flucloxacillin reduced both the CFU counts (3 Log10 CFU/coupon) and biomass (−70%) in one MSSA only, while vancomycin had no effects against MRSA. PL combined with a 24 h reincubation with vancomycin or flucloxacillin at 20 mg/L was synergistic (−5 to 6.5 Log10 CFU/coupon; 81–100% biomass reduction). Fluorescence microscopy confirmed that PL removed most of the biofilm and that subsequent antibiotic treatment partially killed bacteria.Conclusions: While PL only transiently reduces the bacterial load and antibiotics at clinically relevant concentrations show no or limited activity on biofilms, their combination is synergistic against MRSA and MSSA biofilms. These results highlight the need for thorough PL before antibiotic administration in PJI.https://www.frontiersin.org/article/10.3389/fmed.2020.00527/fullbiofilmMRSAMSSApulsed lavagevancomycinflucloxacillin
spellingShingle Hervé Poilvache
Hervé Poilvache
Hervé Poilvache
Albert Ruiz-Sorribas
George Sakoulas
Hector Rodriguez-Villalobos
Olivier Cornu
Olivier Cornu
Françoise Van Bambeke
Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
Frontiers in Medicine
biofilm
MRSA
MSSA
pulsed lavage
vancomycin
flucloxacillin
title Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
title_full Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
title_fullStr Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
title_full_unstemmed Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
title_short Synergistic Effects of Pulsed Lavage and Antimicrobial Therapy Against Staphylococcus aureus Biofilms in an in-vitro Model
title_sort synergistic effects of pulsed lavage and antimicrobial therapy against staphylococcus aureus biofilms in an in vitro model
topic biofilm
MRSA
MSSA
pulsed lavage
vancomycin
flucloxacillin
url https://www.frontiersin.org/article/10.3389/fmed.2020.00527/full
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