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

Une meilleure qualit\ue9 de l'air gr\ue2ce \ue0 une ventilation saine

Also available in English: Air quality and healthy ventilationPeer reviewed: NoNRC publication: Ye

Air quality and healthy ventilation

Aussi disponible en fran\ue7ais: Une meilleure qualit\ue9 de l?air gr\ue2ce \ue0 une ventilation sainePeer reviewed: NoNRC publication: Ye

Indoor air quality and mould

This presentation reviewed the published literature to summarize the currently worldwide suggested standards, guidelines and recommendations for acceptable levels of gaseous organic and inorganic contaminants, and airborne mould spores in indoor environments.Dans cette pr\ue9sentation, on a r\ue9vis\ue9 la litt\ue9rature internationale pour r\ue9sumer les normes, les lignes directrice et les recommandations au niveau des concentrations acceptables des polluants d'air gazeuses organiques et inorganiques, et au niveau des spores de moisissures dans les environnements int\ue9rieurs.Peer reviewed: NoNRC publication: Ye

Vergleich mykologischer und chemisch-analytischer Labormethoden zum Nachweis von Schimmelpilzbefällen in Innenräumen

Für die Bewertung der prädiktiven Wertigkeit häufig angewandter Methoden, die zum Nachweis von Schimmelpilzbefällen in Innenräumen eingesetzt werden, wurden in 45 Schimmel- und in 47 Nichtschimmelwohnungen mykologische und chemisch- analytische Untersuchungen vorgenommen. Die Studie wurde laborverblindet in Bezug auf den durch Inspektion ermittelten Schimmelstatus der Wohnungen durchgeführt. Die Ergebnisse der einzelnen Bestimmungsmethoden wurden anhand ihrer Receiver Operating Characteristic-(ROC-)Kurven miteinander verglichen. Im Ergebnis dieser statistischen Analyse zeigte sich, dass die etablierten mykologischen Bestimmungsmethoden: Erfassung luftgetragener Schimmelpilze mit dem Andersen-Impaktor, sedimentierender Schimmelpilze auf Petri-Schalen und sedimentierter Schimmelpilze in Hausstaub unter den gewählten Studienbedingungen eine hohe diskriminatorische Fähigkeit zur Unterscheidung von Schimmel- und Nichtschimmelwohnungen besitzen, wenn ein Summenscore aus den Gattungen Aspergillus und Penicillium verwendet wurde. Die errechneten Flächen unter den jeweiligen ROC-Kurven (AUC) reichten von AUC=0,992 (95%-KI 0,942–0,997) für die Methode der Bestimmung sedimentierter Pilze im Hausstaub über AUC=0,996 (95%-KI 0,940–0,998) für das Sedimentationsverfahren bis zu AUC=0,999 (95%-KI 0,957– 1,000) für die Methode der Erfassung luftgetragener Schimmelpilze mittels Andersen- Impaktor. Im paarweisen Vergleich erwiesen sich diese Flächen unter den ROC-Kurven als nicht statistisch signifikant voneinander verschieden. Diese Ergebnisse wurden mit DG-18-Agar als Kulturmedium erzielt. Gleichwertige Ergebnisse ergaben sich für Malzextrakt-Agar. Im Vergleich dazu war die Methode der Bestimmung von mikrobiell bedingten flüchtigen organischen Verbindungen (MVOC) mithilfe eines aus 8 Einzelverbindungen gebildeten Summenwertes den mykologischen Verfahren deutlich unterlegen: AUC=0,620 (95%-KI 0,509–0,723). Betrachtet man die untere Grenze des 95%-Konfidenzintervalls der Fläche unter der ROC-Kurve, so ist diese kaum von 0,5 verschieden. Dieses Ergebnis bedeutet, dass sich die Diskriminationsfähigkeit dieser Methode nur geringfügig von der einer zufälligen Klassifizierung unterscheidet. Mögliche methodische Einflüsse, die zu dieser Einschätzung geführt haben, werden diskutiert.To evaluate frequently used methods that discriminate between moldy and nonmoldy indoor environments, 45 homes with visible mold growth and 47 definitively non-infested homes, both confirmed by inspection, were investigated by microbiological and chemical analytical methods. The study was laboratory blinded in relation to the confirmed mold status of the rooms. Statistical evaluation of the results of the applied mycological methods with the Receiver Operating Characteristic (ROC) curve analysis showed that these methods (impaction, open Petri dish method, and determination of mold spores in house dust samples) performed very well in discriminating between rooms with visible mold growth and nonmoldy rooms when the sum score of the mold genera Aspergillus and Penicillium was used as an indicator. The calculated areas under the ROC curves (AUC) of the three mycological methods were: 0.992 (95% CI 0.942–0.997) for mold spores in house dust samples, 0.996 (95% CI 0.940–0.998) for the open Petri dish method, and 0.999 (95% CI 0.957–1.000) for the determination of airborne spores with the Andersen impactor, respectively. A perfect discrimination would lead to an AUC of 1. These results were obtained with DG 18-agar as well as with malt extract agar. In contrast to the results of the mycological methods, the chemical analytical method under the same study conditions showed a distinctly lower performance in discriminating rooms according to their mold status when a sum score (concentration of eight typical MVOC) was used as an indicator. The area under the ROC curve (AUC) had a value of 0.620 (95% CI 0.509–0.723). A completely useless test would have an AUC of 0.5. As the lower limit of the 95% confidence interval of the area under the ROC curve is close to 0.5, the results obtained with the MVOC method do not differ from the classification results which can be obtained simply by chance. Possible methodological biases which could have lead to this interpretation are discussed

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

Commercial IAQ Sensors and their Performance Requirements for Demand-Controlled Ventilation

A scan of commercial off-the-shelf (COTS) sensors is provided for three indoor pollutants (formaldehyde, volatile organic compounds and radon) based on the information from the literature and manufacturers obtained between July 2008 and February 2009. The performance requirements for sensors are also proposed for a meaningful operation in sensor network systems aimed for ventilation and indoor air quality (V&IAQ) controls. Several COTS sensors meeting the proposed requirements are identified for formaldehyde and radon in this report. The identified formaldehyde COTS detectors have a resolution of 5 to 10 ppb, a detection range of 0 to 1 ppm, and a response time of a few to 30 minutes, and are priced between CDN $1,000 and$7,000. Several real-time continuous radon sensors also meet the pre-defined performance requirements, including a detection range between 20 and 5,000 Bq/m3, a resolution of 10 Bq/m3, and a response time of 2 days, and are priced between CDN $300 and$1,100. No commercial volatile organic compound (VOC) sensors meet the established requirements for VOCs. Several of the identified formaldehyde COTS sensors will be validated in NRC?s labs for their actual sensitivity and selectivity.Un balayage de capteurs standard disponibles sur le march\ue9 (SDM) est fourni pour trois (3) polluants int\ue9rieurs (formald\ue9hyde, compos\ue9s organiques volatils [COV] et radon), bas\ue9 sur l?information issue de la documentation et des fabricants ayant \ue9t\ue9 obtenue entre juillet 2008 et f\ue9vrier 2009. Les exigences li\ue9es \ue0 la performance des capteurs sont \ue9galement propos\ue9es pour une exploitation pertinente de ceux-ci dans les syst\ue8mes de r\ue9seaux, visant les contr\uf4les de la ventilation et de la qualit\ue9 de l?air \ue0 l?int\ue9rieur. On identifie dans ce rapport plusieurs capteurs SDM satisfaisant aux exigences propos\ue9es pour le formald\ue9hyde et le radon. Les capteurs SDM identifi\ue9s pour le formald\ue9hyde ont une r\ue9solution de 5 \ue0 10 ppb, une plage de d\ue9tection de 0 \ue0 1 ppm et un temps de r\ue9ponse de quelques minutes \ue0 30 minutes; leur prix varie de 1 000 \ue0 7 000 CAN. Plusieurs capteurs de radon continus en temps r\ue9el r\ue9pondent \ue9galement aux exigences de performance pr\ue9d\ue9finies, y compris une plage de d\ue9tection comprise entre 20 et 5 000 Bq/m3, une r\ue9solution de 10 Bq/m3 et un temps de r\ue9ponse de deux (2) jours, et ils co\ufbtent \ue0 l?achat de 300 \ue0 1 100 CAN. Aucun capteur commercial de COV ne satisfait aux exigences \ue9tablies pour les COV. Plusieurs des capteurs SDM de formald\ue9hyde qui ont \ue9t\ue9 identifi\ue9s seront valid\ue9s dans les laboratoires du CNRC quant \ue0 leur sensibilit\ue9 et \ue0 leur s\ue9lectivit\ue9 r\ue9elles.Peer reviewed: NoNRC publication: Ye