Background: Major alterations in linezolid pharmacokinetic/pharmacodynamic (PK/PD) parameters might be expected\nin critically ill septic patients with acute kidney injury (AKI) who are undergoing continuous renal replacement therapy\n(CRRT). The present review is aimed at describing extracorporeal removal of linezolid and the main PK-PD parameter\nchanges observed in critically ill septic patients with AKI, who are on CRRT.\nMethod: Citations published on PubMed up to January 2016 were systematically reviewed according to the preferred\nreporting items for systematic reviews and meta-analyses (PRISMA) statement. All authors assessed the methodological\nquality of the studies and consensus was used to ensure studies met inclusion criteria. In-vivo studies in adult patients\nwith AKI treated with linezolid and on CRRT were considered eligible for the analysis only if operational settings of the\nCRRT machine, membrane type, linezolid blood concentrations and main PK-PD parameters were all clearly reported.\nResults: Among 68 potentially relevant articles, only 9 were considered eligible for the analysis. Across these, 53\ntreatments were identified among the 49 patients included (46 treated with high-flux and 3 with high cut-off\nmembranes). Continuous veno-venous hemofiltration (CVVH) was the most frequent treatment performed amongst\nthe studies. The extracorporeal clearance values of linezolid across the different modalities were 1.2ââ?¬â??2.3 L/h for CVVH,\n0.9ââ?¬â??2.2 L/h for hemodiafiltration and 2.3 L/h for hemodialysis, and large variability in PK/PD parameters was reported.\nThe optimal area under the curve/minimum inhibitory concentration (AUC/MIC) ratio was reached for pathogens with\nan MIC of 4 mg/L in one study only.\nConclusions: Wide variability in linezolid PK/PD parameters has been observed across critically ill septic patients with\nAKI treated with CRRT. Particular attention should be paid to linezolid therapy in order to avoid antibiotic failure in\nthese patients. Strategies to improve the effectiveness of this antimicrobial therapy (such as routine use of target drug\nmonitoring, increased posology or extended infusion) should be carefully evaluated, both in clinical and research\nsettings.
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