Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model
Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibio...
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| Format: | Article |
| Language: | English |
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Frontiers Media S.A.
2018-03-01
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| Series: | Frontiers in Microbiology |
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| Online Access: | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00572/full |
| _version_ | 1819151775510298624 |
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| author | Diane C. Broussou Diane C. Broussou Marlène Z. Lacroix Pierre-Louis Toutain Frédérique Woehrlé Farid El Garch Alain Bousquet-Melou Aude A. Ferran |
| author_facet | Diane C. Broussou Diane C. Broussou Marlène Z. Lacroix Pierre-Louis Toutain Frédérique Woehrlé Farid El Garch Alain Bousquet-Melou Aude A. Ferran |
| author_sort | Diane C. Broussou |
| collection | DOAJ |
| description | Combining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments. |
| first_indexed | 2024-12-22T14:38:45Z |
| format | Article |
| id | doaj.art-dc7c139e370643bcb3268345274d7c80 |
| institution | Directory Open Access Journal |
| issn | 1664-302X |
| language | English |
| last_indexed | 2024-12-22T14:38:45Z |
| publishDate | 2018-03-01 |
| publisher | Frontiers Media S.A. |
| record_format | Article |
| series | Frontiers in Microbiology |
| spelling | doaj.art-dc7c139e370643bcb3268345274d7c802022-12-21T18:22:36ZengFrontiers Media S.A.Frontiers in Microbiology1664-302X2018-03-01910.3389/fmicb.2018.00572310341Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection ModelDiane C. Broussou0Diane C. Broussou1Marlène Z. Lacroix2Pierre-Louis Toutain3Frédérique Woehrlé4Farid El Garch5Alain Bousquet-Melou6Aude A. Ferran7INTHERES, INRA, ENVT, Université de Toulouse, Toulouse, FranceVétoquinol, Global Drug Development, Lure, FranceINTHERES, INRA, ENVT, Université de Toulouse, Toulouse, FranceDepartment of Veterinary Basic Sciences, Royal Veterinary College, London, United KingdomVétoquinol, Global Drug Development, Lure, FranceVétoquinol, Global Drug Development, Lure, FranceINTHERES, INRA, ENVT, Université de Toulouse, Toulouse, FranceINTHERES, INRA, ENVT, Université de Toulouse, Toulouse, FranceCombining currently available antibiotics to optimize their use is a promising strategy to reduce treatment failures against biofilm-associated infections. Nevertheless, most assays of such combinations have been performed in vitro on planktonic bacteria exposed to constant concentrations of antibiotics over only 24 h and the synergistic effects obtained under these conditions do not necessarily predict the behavior of chronic clinical infections associated with biofilms. To improve the predictivity of in vitro combination assays for bacterial biofilms, we first adapted a previously described Hollow-fiber (HF) infection model by allowing a Staphylococcus aureus biofilm to form before drug exposure. We then mimicked different concentration profiles of amikacin and vancomycin, similar to the free plasma concentration profiles that would be observed in patients treated daily over 5 days. We assessed the ability of the two drugs, alone or in combination, to reduce planktonic and biofilm-embedded bacterial populations, and to prevent the selection of resistance within these populations. Although neither amikacin nor vancomycin exhibited any bactericidal activity on S. aureus in monotherapy, the combination had a synergistic effect and significantly reduced the planktonic bacterial population by -3.0 to -6.0 log10 CFU/mL. In parallel, no obvious advantage of the combination, as compared to amikacin alone, was demonstrated on biofilm-embedded bacteria for which the addition of vancomycin to amikacin only conferred a further maximum reduction of 0.3 log10 CFU/mL. No resistance to vancomycin was ever found whereas a few bacteria less-susceptible to amikacin were systematically detected before treatment. These resistant bacteria, which were rapidly amplified by exposure to amikacin alone, could be maintained at a low level in the biofilm population and even suppressed in the planktonic population by adding vancomycin. In conclusion, by adapting the HF model, we were able to demonstrate the different bactericidal activities of the vancomycin and amikacin combination on planktonic and biofilm-embedded bacterial populations, suggesting that, for biofilm-associated infections, the efficacy of this combination would not be much greater than with amikacin monotherapy. However, adding vancomycin could reduce possible resistance to amikacin and provide a relevant strategy to prevent the selection of antibiotic-resistant bacteria during treatments.http://journal.frontiersin.org/article/10.3389/fmicb.2018.00572/fullhollow-fiber infection modelantibiotic combinationamikacinvancomycinbiofilmantimicrobial resistance |
| spellingShingle | Diane C. Broussou Diane C. Broussou Marlène Z. Lacroix Pierre-Louis Toutain Frédérique Woehrlé Farid El Garch Alain Bousquet-Melou Aude A. Ferran Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model Frontiers in Microbiology hollow-fiber infection model antibiotic combination amikacin vancomycin biofilm antimicrobial resistance |
| title | Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model |
| title_full | Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model |
| title_fullStr | Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model |
| title_full_unstemmed | Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model |
| title_short | Differential Activity of the Combination of Vancomycin and Amikacin on Planktonic vs. Biofilm-Growing Staphylococcus aureus Bacteria in a Hollow Fiber Infection Model |
| title_sort | differential activity of the combination of vancomycin and amikacin on planktonic vs biofilm growing staphylococcus aureus bacteria in a hollow fiber infection model |
| topic | hollow-fiber infection model antibiotic combination amikacin vancomycin biofilm antimicrobial resistance |
| url | http://journal.frontiersin.org/article/10.3389/fmicb.2018.00572/full |
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