Tigecycline in critically ill patients on continuous renal replacement therapy: a population pharmacokinetic study

Background: Tigecycline is a vital antibiotic treatment option for infections caused by multiresistant bacteria in the intensive care unit (ICU). Acute kidney injury (AKI) is a common complication in the ICU requiring continuous renal replacement therapy (CRRT), but pharmacokinetic data for tigecycline in patients receiving CRRT are lacking. Methods: Eleven patients mainly with intra-abdominal infections receiving either continuous veno-venous hemodialysis (CVVHD, n = 8) or hemodiafiltration (CVVHDF, n = 3) were enrolled, and plasma as well as effluent samples were collected according to a rich sampling schedule. Total and free tigecycline was determined by ultrafiltration and high-performance liquid chromatography (HPLC)-UV. Population pharmacokinetic modeling using NONMEM® 7.4 was used to determine the pharmacokinetic parameters as well as the clearance of CVVHD and CVVHDF. Pharmacokinetic/pharmacodynamic target attainment analyses were performed to explore the potential need for dose adjustments of tigecycline in CRRT. Results: A two-compartment population pharmacokinetic (PK) model was suitable to simultaneously describe the plasma PK and effluent measurements of tigecycline. Tigecycline dialysability was high, as indicated by the high mean saturation coefficients of 0.79 and 0.90 for CVVHD and CVVHDF, respectively, and in range of the concentration-dependent unbound fraction of tigecycline (45–94%). However, the contribution of CRRT to tigecycline clearance (CL) was only moderate (CLCVVHD: 1.69 L/h, CLCVVHDF: 2.71 L/h) in comparison with CLbody (physiological part of the total clearance) of 18.3 L/h. Bilirubin was identified as a covariate on CLbody in our collective, reducing the observed interindividual variability on CLbody from 58.6% to 43.6%. The probability of target attainment under CRRT for abdominal infections was ≥ 0.88 for minimal inhibitory concentration (MIC) values ≤ 0.5 mg/L and similar to patients without AKI. Conclusions: Despite high dialysability, dialysis clearance displayed only a minor contribution to tigecycline elimination, being in the range of renal elimination in patients without AKI. No dose adjustment of tigecycline seems necessary in CRRT. Trial registration: EudraCT, 2012–005617-39. Registered on 7 August 2013

Newsbrief - NRC-IRC researchers study mould growth in buildings

Aussi disponible en fran\ue7ais: En bref - des chercheurs de l'IRC-CNRC \ue9tudient la formation de moisissures dans les b\ue2timentsPeer reviewed: NoNRC publication: Ye

Environnement int\ue9rieur: mieux conna\ueetre pour mieux pr\ue9venir! Partie II. La recherche sur les moisissures au Conseil national de recherche du Canada

The National Research Council of Canada (NRC-IRC) has initiated a series of research projects to address the issue of mould growth in buildings, an unacceptable state of affairs. For this reason, NRC-IRC is perfecting new research facilities and improving existing ones to contribute to information gathering in the following fields:1) Drawing up tried and tested methods to detect mould growth in buildings2) Performing tests to establish mould resistance of construction materials3) Forecasting mould growth on materials and building components4) Healthy ventilation systems5) Corrective remediation measuresLe Conseil national de recherches Canada (IRC-CNRC) a lanc\ue9 une s\ue9rie de projets de recherche concernant la formation de moisissures dans les b\ue2timents, puisqu'il est admis que la formation de moisissures n'est pas acceptable. Pour cette raison, l'IRC-CNRC met au point de nouvelles installations de recherche et am\ue9liore des installations existantes pour contribuer aux connaissances dans les domaines suivants:1) \ue9laboration de m\ue9thodes \ue9prouv\ue9es pour la d\ue9tection de moisissures dans les b\ue2timents;2) essais de d\ue9termination de la r\ue9sistance aux moisissures des mat\ue9riaux de construction;3) pr\ue9diction de la formation de moisissures sur les mat\ue9riaux et les \ue9l\ue9ments de b\ue2timent;4) syst\ue8mes de ventilation sains;5) m\ue9thodes correctives pour la remise en \ue9tat.Peer reviewed: NoNRC publication: Ye

The IVAIRE project: ventilation characteristics of single homes of asthmatic children followed in an asthma clinic

Peer reviewed: NoNRC publication: Ye

The IVAIRE project: a randomized controlled study on the impact of ventilation on indoor air quality and the respiratory symptoms of asthmatic children in residential buildings: health aspects

Peer reviewed: NoNRC publication: Ye

The IVAIRE Project: a randomized controlled study on the impact of ventilation on IAQ and the symptoms of asthmatic children in single family homes: environmental aspects

Peer reviewed: NoNRC publication: Ye