Effects of Tigecycline and Doxycycline on Inflammation and Hemodynamics in Porcine Endotoxemia: a Prospective, Randomized and Placebo Controlled Trial
2015 (English)In: Shock, ISSN 1073-2322, E-ISSN 1540-0514, Vol. 43, no 6, 604-611 p.Article in journal (Refereed) Published
BACKGROUND: Antibiotics might, apart from an antimicrobial effect, also exert anti-inflammatory effects. The novel antibiotic tigecycline, potentially useful in septic shock from Gram-negative multi-resistant bacteria, is structurally related to antibiotics with known anti-inflammatory properties. However, its anti-inflammatory effects have previously not been explored in vivo. Using a sterile integrative porcine sepsis model, we investigated the anti-inflammatory and circulatory effects of tigecycline in comparison to doxycycline and placebo.
METHODS: 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 x kg x h. Markers of inflammation, nitric oxide (NO) production, vascular permeability, hemodynamics, organ dysfunction, tissue metabolism and acid-base parameters were monitored.
RESULTS: Peak plasma tumor necrosis alpha (TNF-α) was lower in the doxycycline group (P=0.031) but not in the tigecycline group (P=0.86) compared to placebo with geometric mean plasma concentrations of 16, 79 and 63 ng x ml, respectively. Mean arterial pressure was higher 4-6 h in the tigecycline group with values at 6 h of 107± 9 mmHg compared to 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 4-6 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.
CONCLUSIONS: Consistent with known anti-inflammatory properties, doxycycline yielded decreased TNF-α levels. Tigecycline did not affect cytokine levels but counteracted hypotension and hypoperfusion.
Place, publisher, year, edition, pages
2015. Vol. 43, no 6, 604-611 p.
Anesthesiology and Intensive Care
IdentifiersURN: urn:nbn:se:uu:diva-244766DOI: 10.1097/SHK.0000000000000351ISI: 000354734300013PubMedID: 25664982OAI: oai:DiVA.org:uu-244766DiVA: diva2:789831