A high-dose aminoglycoside regimen combined with renal replacement therapy for the treatment of MDR pathogens: a proof-of-concept study.
J Antimicrob Chemother. 2016 Jan 31;
Authors: Brasseur A, Hites M, Roisin S, Cotton F, Vincent JL, De Backer D, Jacobs F, Taccone FS
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.
PMID: 26832751 [PubMed - as supplied by publisher]