Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model
Copyright: © 2023 Johansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited..
OBJECTIVES: We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy.
MATERIALS AND METHODS: Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration.
RESULTS: All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24).
CONCLUSION: We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2023 |
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| Erschienen: |
2023 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:18 |
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| Enthalten in: |
PloS one - 18(2023), 7 vom: 01., Seite e0287671 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
Johansen, Mikkel Illemann [VerfasserIn] |
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| Links: |
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| Themen: |
6Q205EH1VU |
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| Anmerkungen: |
Date Completed 02.10.2023 Date Revised 02.10.2023 published: Electronic-eCollection Citation Status MEDLINE |
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| doi: |
10.1371/journal.pone.0287671 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM35963625X |
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| 100 | 1 | |a Johansen, Mikkel Illemann |e verfasserin |4 aut | |
| 245 | 1 | 0 | |a Fibrinolytic and antibiotic treatment of prosthetic vascular graft infections in a novel rat model |
| 264 | 1 | |c 2023 | |
| 336 | |a Text |b txt |2 rdacontent | ||
| 337 | |a ƒaComputermedien |b c |2 rdamedia | ||
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| 500 | |a Date Completed 02.10.2023 | ||
| 500 | |a Date Revised 02.10.2023 | ||
| 500 | |a published: Electronic-eCollection | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Copyright: © 2023 Johansen et al. This is an open access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited. | ||
| 520 | |a OBJECTIVES: We developed a rat model of prosthetic vascular graft infection to assess, whether the fibrinolytic tissue plasminogen activator (tPA) could increase the efficacy of antibiotic therapy | ||
| 520 | |a MATERIALS AND METHODS: Rats were implanted a polyethylene graft in the common carotid artery, pre-inoculated with approx. 6 log10 colony forming units (CFU) of methicillin resistant Staphylococcus aureus. Ten days after surgery, rats were randomized to either: 0.9% NaCl (n = 8), vancomycin (n = 8), vancomycin + tPA (n = 8), vancomycin + rifampicin (n = 18) or vancomycin + rifampicin + tPA (n = 18). Treatment duration was seven days. Approximately 36 hours after the end of treatment, the rats were euthanized, and grafts and organs were harvested for CFU enumeration | ||
| 520 | |a RESULTS: All animals in the control group had significantly higher CFU at the time of euthanization compared to bacterial load found on the grafts prior to inoculation (6.45 vs. 4.36 mean log10 CFU/mL, p = 0.0011), and both the procedure and infection were well tolerated. Vancomycin and rifampicin treatment were superior to monotherapy with vancomycin, as it lead to a marked decrease in median bacterial load on the grafts (3.50 vs. 6.56 log10 CFU/mL, p = 0.0016). The addition of tPA to vancomycin and rifampicin combination treatment did not show a further decrease in bacterial load (4.078 vs. 3.50 log10 CFU/mL, p = 0.26). The cure rate was 16% in the vancomycin + rifampicin group vs. 37.5% cure rate in the vancomycin + rifampicin + tPA group. Whilst interesting, this trend was not significant at our sample size (p = 0.24) | ||
| 520 | |a CONCLUSION: We developed the first functional model of an arterial prosthetic vascular graft infection in rats. Antibiotic combination therapy with vancomycin and rifampicin was superior to vancomycin monotherapy, and the addition of tPA did not significantly reduce bacterial load, nor significantly increase cure rate | ||
| 650 | 4 | |a Journal Article | |
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| 650 | 7 | |a Rifampin |2 NLM | |
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| 650 | 7 | |a Tissue Plasminogen Activator |2 NLM | |
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| 650 | 7 | |a Vancomycin |2 NLM | |
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| 700 | 1 | |a Rahbek, Søren Jensen |e verfasserin |4 aut | |
| 700 | 1 | |a Jensen-Fangel, Søren |e verfasserin |4 aut | |
| 700 | 1 | |a Minero, Gabriel Antonio S |e verfasserin |4 aut | |
| 700 | 1 | |a Jensen, Louise Kruse |e verfasserin |4 aut | |
| 700 | 1 | |a Larsen, Ole Halfdan |e verfasserin |4 aut | |
| 700 | 1 | |a Erikstrup, Lise Tornvig |e verfasserin |4 aut | |
| 700 | 1 | |a Seefeldt, Anders Marthinsen |e verfasserin |4 aut | |
| 700 | 1 | |a Østergaard, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Meyer, Rikke Louise |e verfasserin |4 aut | |
| 700 | 1 | |a Jørgensen, Nis Pedersen |e verfasserin |4 aut | |
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