Abstract
BackgroundMajor alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT.MethodCitations published on PubMed up to January 2016 were systematically reviewed according to the preferred reporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological quality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients with AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the CRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported.ResultsAmong 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53 treatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off membranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst the studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2–2.3 L/h for CVVH, 0.9–2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported. The optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with an MIC of 4 mg/L in one study only.ConclusionsWide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with AKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in these patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug monitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research settings.
Highlights
Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT)
This systematic review describes the parameters of extracorporeal removal of linezolid in the course of different modalities of CRRT, and of derangements in PK parameters in critically ill patients with sepsis and AKI, who are on CRRT
Qd dialysate flow, Qf replacement flow, QfNET net ultrafiltration flow, UFNET net ultrafiltrate, BW body weight, APACHE II Acute Physiology and Chronic Health Evaluation II, SOFA Sequential Organ Failure Assessment, SA/SC saturation coefficient or sieving coefficient, Qeff effluent flow, XCRRT total amount of drug eliminated by the extracorporeal treatment, CLCRRT extracorporeal clearance, Cmax antibiotic maximum serum concentration, Cmin antibiotic trough, T1/2 elimination half-life, AUC area under the curve, Vd volume of distribution, CLtot total clearance
Summary
Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected in critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy (CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter changes observed in critically ill septic patients with AKI, who are on CRRT. Sepsis is frequently observed in the intensive care unit (ICU), and it is one of the major causes of death among critically ill patients [1,2,3,4]. Linezolid has been shown to be efficacious against these micro-organisms and, it is frequently used in ICU patients [7, 8]. A T > MIC of ≥85 and an AUC0–24/MIC >100 are required to exert maximal antimicrobial efficacy, and are associated with better clinical outcome in severely ill patients [13]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
