Effects of tigecycline and doxycycline on inflammation and hemodynamics in porcine endotoxemia : a prospective, randomized, and placebo-controlled trial
Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from gram-negative multiresistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have not been previously explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison with doxycycline and placebo. Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg, or placebo and subjected to 6-h endotoxin infusion at 0.5 μg kg(-1) h(-1). Markers of inflammation, nitric oxide production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism, and acid-base parameters were monitored. Peak plasma tumor necrosis factor-α was lower in the doxycycline group (P = 0.031) but not in the tigecycline group (P = 0.86) compared with placebo, with geometric mean plasma concentrations of 16, 79, and 63 ng mL(-1), respectively. Mean arterial pressure was higher 4 to 6 h in the tigecycline group, with values at 6 h of 107 ± 9 mmHg compared with the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively; P = 0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group but not in the tigecycline group at 4 to 6 h (P = 0.009 and P = 0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism, and acid-base parameters were unaffected by tigecycline. Consistent with known anti-inflammatory properties, doxycycline yielded decreased tumor necrosis factor-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.
| Medienart: |
E-Artikel |
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| Erscheinungsjahr: |
2015 |
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| Erschienen: |
2015 |
| Enthalten in: |
Zur Gesamtaufnahme - volume:43 |
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| Enthalten in: |
Shock (Augusta, Ga.) - 43(2015), 6 vom: 03. Juni, Seite 604-11 |
| Sprache: |
Englisch |
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| Beteiligte Personen: |
von Seth, Magnus [VerfasserIn] |
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| Links: |
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| Themen: |
70JE2N95KR |
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| Anmerkungen: |
Date Completed 25.04.2016 Date Revised 02.12.2018 published: Print Citation Status MEDLINE |
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| doi: |
10.1097/SHK.0000000000000351 |
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| funding: |
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| Förderinstitution / Projekttitel: |
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| PPN (Katalog-ID): |
NLM246077603 |
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| 500 | |a published: Print | ||
| 500 | |a Citation Status MEDLINE | ||
| 520 | |a Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from gram-negative multiresistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have not been previously explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison with doxycycline and placebo. Eighteen pigs were randomized to receive tigecycline 100 mg, doxycycline 200 mg, or placebo and subjected to 6-h endotoxin infusion at 0.5 μg kg(-1) h(-1). Markers of inflammation, nitric oxide production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism, and acid-base parameters were monitored. Peak plasma tumor necrosis factor-α was lower in the doxycycline group (P = 0.031) but not in the tigecycline group (P = 0.86) compared with placebo, with geometric mean plasma concentrations of 16, 79, and 63 ng mL(-1), respectively. Mean arterial pressure was higher 4 to 6 h in the tigecycline group, with values at 6 h of 107 ± 9 mmHg compared with the placebo and doxycycline groups (85 ± 27 mmHg and 90 ± 32 mmHg, respectively; P = 0.025). The white blood cell and the neutrophil granulocyte counts were less reduced in the doxycycline group but not in the tigecycline group at 4 to 6 h (P = 0.009 and P = 0.019, respectively). Other markers of inflammation, organ dysfunction, tissue metabolism, and acid-base parameters were unaffected by tigecycline. Consistent with known anti-inflammatory properties, doxycycline yielded decreased tumor necrosis factor-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion | ||
| 650 | 4 | |a Journal Article | |
| 650 | 7 | |a Tigecycline |2 NLM | |
| 650 | 7 | |a 70JE2N95KR |2 NLM | |
| 650 | 7 | |a Minocycline |2 NLM | |
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| 650 | 7 | |a Doxycycline |2 NLM | |
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| 700 | 1 | |a Sjölin, Jan |e verfasserin |4 aut | |
| 700 | 1 | |a Larsson, Anders |e verfasserin |4 aut | |
| 700 | 1 | |a Eriksson, Mats |e verfasserin |4 aut | |
| 700 | 1 | |a Hillered, Lars |e verfasserin |4 aut | |
| 700 | 1 | |a Lipcsey, Miklós |e verfasserin |4 aut | |
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