In vitro activity of antibiotic monotherapy and combination therapy with bacteriophages against Staphylococcus aureus LVAD-driveline infections
Current treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro a...
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| Vydané v: | Journal of clinical microbiology Ročník 63; číslo 11; s. e0027225 |
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| Hlavní autori: | , , , , , , , , , , |
| Médium: | Journal Article |
| Jazyk: | English |
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United States
American Society for Microbiology
12.11.2025
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| ISSN: | 0095-1137, 1098-660X, 1098-660X |
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| Abstract | Current treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections. |
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| AbstractList | Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. Staphylococcus aureus (S. aureus) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel in vitro assay was developed to study the antibiotic susceptibility of S. aureus biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the S. aureus biofilms to antibiotic monotherapy compared to planktonic S. aureus. With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against S. aureus biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against S. aureus in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.IMPORTANCECurrent treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections.Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. Staphylococcus aureus (S. aureus) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel in vitro assay was developed to study the antibiotic susceptibility of S. aureus biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the S. aureus biofilms to antibiotic monotherapy compared to planktonic S. aureus. With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against S. aureus biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against S. aureus in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.IMPORTANCECurrent treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections. Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. ( ) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel assay was developed to study the antibiotic susceptibility of biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the biofilms to antibiotic monotherapy compared to planktonic . With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.IMPORTANCECurrent treatment strategies for LVAD-driveline infections are based on antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between antibiotic susceptibility and treatment success. Here, we have developed a novel assay to determine antibiotic susceptibility of biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving treatment strategies for LVAD-driveline infections. Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. Staphylococcus aureus (S. aureus) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel in vitro assay was developed to study the antibiotic susceptibility of S. aureus biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the S. aureus biofilms to antibiotic monotherapy compared to planktonic S. aureus. With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against S. aureus biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against S. aureus in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.IMPORTANCECurrent treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections. Current treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections. ABSTRACT Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the driveline, are susceptible to difficult-to-treat infections, associated with high morbidity and mortality rates. Staphylococcus aureus (S. aureus) is a major causative pathogen of LVAD infections. Antibiotic resistance and biofilm formation can complicate the treatment of these infections. A novel in vitro assay was developed to study the antibiotic susceptibility of S. aureus biofilm grown on LVAD drivelines. Besides antibiotic monotherapy, the effect of various antibiotics combined with rifampicin was studied. Additionally, we explored the efficacy of four individual phages and phage-antibiotic combinations as potential treatment strategies. Our data showed a decrease of susceptibility of the S. aureus biofilms to antibiotic monotherapy compared to planktonic S. aureus. With only rifampicin and erythromycin monotherapy resulting in full bacterial clearance. Combining antibiotics with rifampicin showed similar antimicrobial efficacy against S. aureus biofilms as rifampicin monotherapy. While both individual phages and a phage cocktail were effective against planktonic bacteria, phage efficacy was limited against S. aureus in biofilm. Combining phages with antibiotics did not clearly improve treatment efficacy, compared to antibiotic monotherapy. Contrarily, it even increased bacterial growth when phage administration preceded antibiotic treatment. Here, both antibiotic- and phage monotherapy showed reduced efficacy on LVAD-driveline biofilms. Additionally, phages did not show an additive value to antibiotic treatment of LVAD driveline infections. Further studies are needed to elucidate optimal treatment strategies for LVAD-driveline infections.IMPORTANCECurrent treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD infections are most often biofilm-related, which decreases antibiotic susceptibility significantly, resulting in discrepancies between in vitro antibiotic susceptibility and in vivo treatment success. Here, we have developed a novel in vitro assay to determine antibiotic susceptibility of S. aureus biofilm, grown in conditions relevant to LVAD-driveline infections. Next to antibiotic susceptibility, the susceptibility of this biofilm to bacteriophage mono- and combination treatment with antibiotics was evaluated as an alternative treatment strategy. In the future, this assay can be used to provide a better insight in in vivo antibiotic- and bacteriophage susceptibility of LVAD-driveline biofilms. Thereby improving in vivo treatment strategies for LVAD-driveline infections. |
| Author | Caliskan, Kadir van Wamel, Willem J. B. de Vogel, Corné P. Verkaik, Nelianne J. Bode, Lonneke G. M. de Graaf, Miranda Verbon, Annelies Knight, Gwenan M. Koopmans, Marion P. G. Molendijk, Michèle M. Lemmens-den Toom, Nicole |
| Author_xml | – sequence: 1 givenname: Michèle M. orcidid: 0000-0001-8225-7384 surname: Molendijk fullname: Molendijk, Michèle M. – sequence: 2 givenname: Nelianne J. surname: Verkaik fullname: Verkaik, Nelianne J. – sequence: 3 givenname: Corné P. surname: de Vogel fullname: de Vogel, Corné P. – sequence: 4 givenname: Nicole surname: Lemmens-den Toom fullname: Lemmens-den Toom, Nicole – sequence: 5 givenname: Gwenan M. surname: Knight fullname: Knight, Gwenan M. – sequence: 6 givenname: Kadir surname: Caliskan fullname: Caliskan, Kadir – sequence: 7 givenname: Lonneke G. M. surname: Bode fullname: Bode, Lonneke G. M. – sequence: 8 givenname: Annelies surname: Verbon fullname: Verbon, Annelies – sequence: 9 givenname: Marion P. G. surname: Koopmans fullname: Koopmans, Marion P. G. – sequence: 10 givenname: Miranda orcidid: 0000-0002-7831-0098 surname: de Graaf fullname: de Graaf, Miranda – sequence: 11 givenname: Willem J. B. orcidid: 0000-0001-9145-9121 surname: van Wamel fullname: van Wamel, Willem J. B. |
| BackLink | https://www.ncbi.nlm.nih.gov/pubmed/41065359$$D View this record in MEDLINE/PubMed |
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| Keywords | LVAD driveline infection Staphylococcus aureus bacteriophages biofilm isothermal microcalorimetry |
| Language | English |
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| Snippet | Current treatment strategies for S. aureus LVAD-driveline infections are based on in vitro antibiotic susceptibility of planktonic bacteria. However, LVAD... Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially the... ABSTRACT Left-ventricular assist devices (LVADs) are increasingly used as a bridge to heart transplantation and destination therapy. These devices, especially... |
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| SubjectTerms | Animal Models of Infection Anti-Bacterial Agents - pharmacology Antimicrobial Resistance Bacterial Infections Bacteriology Bacteriophage-Pathogen Interactions Bacteriophages Bacteriophages - physiology biofilm Biofilm-Associated Resistance Biofilms - drug effects Biofilms - growth & development Clinical Microbiology and Infectious Diseases Heart-Assist Devices - adverse effects Heart-Assist Devices - microbiology Humans isothermal microcalorimetry LVAD driveline infection Microbial Pathogenesis and Immunology Microbial Sensitivity Tests Outbreak Investigation in Healthcare Facilities Phage Therapy Phage Therapy - methods Prosthesis-Related Infections - microbiology Prosthesis-Related Infections - therapy Rifampin - pharmacology Staphylococcal Infections Staphylococcal Infections - microbiology Staphylococcal Infections - therapy Staphylococcus aureus Staphylococcus aureus - drug effects Staphylococcus aureus - physiology Staphylococcus aureus - virology Staphylococcus Phages - physiology Trichinellosis Vaginal Fungal Infections Virology |
| Title | In vitro activity of antibiotic monotherapy and combination therapy with bacteriophages against Staphylococcus aureus LVAD-driveline infections |
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