Alexandre Brasseur1, Maya Hites2, Sandrine Roisin3, Frédéric Cotton4, Jean-Louis Vincent1, Daniel De Backer1, Frédérique Jacobs2, Fabio Silvio Taccone5. 1. Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808-1070 Brussels, Belgium. 2. Department of Infectious Diseases, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808-1070 Brussels, Belgium. 3. Department of Clinical Microbiology, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808-1070 Brussels, Belgium. 4. Department of Clinical Biochemistry, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808-1070 Brussels, Belgium. 5. Department of Intensive Care, Erasme Hospital, Université Libre de Bruxelles, Route de Lennik, 808-1070 Brussels, Belgium ftaccone@ulb.ac.be.
Abstract
BACKGROUND: Infections caused by MDR Gram-negative (GN) organisms in critically ill patients are a therapeutic challenge. The administration of high-dose aminoglycoside (HDA) therapy coupled with high-flow continuous veno-venous haemodiafiltration (CVVHDF) could allow required high drug peaks to be achieved with acceptable drug elimination. METHODS: All adult patients present on the ICU between October 2009 and July 2014 who had MDR GN sepsis were considered for HDA and high-flow (>45 mL/kg/h) CVVHDF when an isolated pathogen was susceptible or had intermediate susceptibility to aminoglycosides and the patient's condition was not improving with conventional therapy. Optimal antibacterial activity was defined as a peak concentration of at least eight times the MIC. RESULTS: Fifteen patients infected with MDR GN pathogens (11 with Pseudomonas aeruginosa; 10 with abdominal infections and 5 with respiratory infections) were treated with amikacin (n = 11), gentamicin (n = 3) or tobramycin (n = 1) and high-flow CVVHDF. A favourable clinical response was observed in eight (53%) patients, including three in whom microbial eradication was obtained. Six patients were discharged alive from the ICU, and five from the hospital. No renal toxicity was observed among survivors. CONCLUSION: In this cohort of septic patients with MDR GN infections, HDA combined with high-flow CVVHDF represented a valuable therapeutic option. The effectiveness of this approach should be further evaluated in larger studies.
BACKGROUND: Infections caused by MDR Gram-negative (GN) organisms in critically illpatients are a therapeutic challenge. The administration of high-dose aminoglycoside (HDA) therapy coupled with high-flow continuous veno-venous haemodiafiltration (CVVHDF) could allow required high drug peaks to be achieved with acceptable drug elimination. METHODS: All adult patients present on the ICU between October 2009 and July 2014 who had MDR GN sepsis were considered for HDA and high-flow (>45 mL/kg/h) CVVHDF when an isolated pathogen was susceptible or had intermediate susceptibility to aminoglycosides and the patient's condition was not improving with conventional therapy. Optimal antibacterial activity was defined as a peak concentration of at least eight times the MIC. RESULTS: Fifteen patients infected with MDR GN pathogens (11 with Pseudomonas aeruginosa; 10 with abdominal infections and 5 with respiratory infections) were treated with amikacin (n = 11), gentamicin (n = 3) or tobramycin (n = 1) and high-flow CVVHDF. A favourable clinical response was observed in eight (53%) patients, including three in whom microbial eradication was obtained. Six patients were discharged alive from the ICU, and five from the hospital. No renal toxicity was observed among survivors. CONCLUSION: In this cohort of septicpatients with MDR GN infections, HDA combined with high-flow CVVHDF represented a valuable therapeutic option. The effectiveness of this approach should be further evaluated in larger studies.
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