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Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a beta-Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model
Stockholm University, Faculty of Science, Department of Molecular Biosciences, The Wenner-Gren Institute.
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2014 (English)In: PLoS ONE, ISSN 1932-6203, E-ISSN 1932-6203, Vol. 9, no 2, e90441- p.Article in journal (Refereed) Published
Abstract [en]

This study aimed to determine whether the addition of an aminoglycoside to a beta-lactam antibiotic increases the antimicrobial effect during the early phase of Gram-negative severe sepsis/septic shock. A porcine model was selected that considered each animal's individual blood bactericidal capacity. Escherichia coli, susceptible to both antibiotics, was given to healthy pigs intravenously during 3 h. At 2 h, the animals were randomized to a 20-min infusion with either cefuroxime alone (n = 9), a combination of cefuroxime+tobramycin (n = 9), or saline (control, n = 9). Blood samples were collected hourly for cultures and quantitative polymerase chain reaction (PCR). Bacterial growth in the organs after 6 h was chosen as the primary endpoint. A blood sample was obtained at baseline before start of bacterial infusion for ex vivo investigation of the blood bactericidal capacity. At 1 h after the administration of the antibiotics, a second blood sample was taken for ex vivo investigation of the antibiotic-induced blood killing activity. All animals developed severe sepsis/septic shock. Blood cultures and PCR rapidly became negative after completed bacterial infusion. Antibiotic-induced blood killing activity was significantly greater in the combination group than in the cefuroxime group (p < 0.001). Growth of bacteria in the spleen was reduced in the two antibiotic groups compared with the controls (p < 0.01); no difference was noted between the two antibiotic groups. Bacterial growth in the liver was significantly less in the combination group than in the cefuroxime group (p < 0.05). High blood bactericidal capacity at baseline was associated with decreased growth in the blood and spleen (p < 0.05). The addition of tobramycin to cefuroxime results in increased antibiotic-induced blood killing activity and less bacteria in the liver than cefuroxime alone. Individual blood bactericidal capacity may have a significant effect on antimicrobial outcome.

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2014. Vol. 9, no 2, e90441- p.
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Biological Sciences
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URN: urn:nbn:se:su:diva-102786DOI: 10.1371/journal.pone.0090441ISI: 000332396200200OAI: oai:DiVA.org:su-102786DiVA: diva2:713541
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AuthorCount:7;

Available from: 2014-04-23 Created: 2014-04-22 Last updated: 2017-12-05Bibliographically approved

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