Beneficial Antimicrobial Effect of the Addition of an Aminoglycoside to a beta -Lactam Antibiotic in an E. coli Porcine Intensive Care Severe Sepsis Model: e90441

• Published in: PloS one Vol. 9; no. 2
• Main Authors: Skorup, Paul, Maudsdotter, Lisa, Lipcsey, Miklos, Castegren, Markus, Larsson, Anders, Jonsson, Ann-Beth, Sjolin, Jan
• Format: Journal Article
• Language: English
• Published: 01.02.2014
• Subjects: Escherichia coli
• ISSN: 1932-6203
• DOI: 10.1371/journal.pone.0090441

This study aimed to determine whether the addition of an aminoglycoside to a s-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.