title: Effects of continuous renal replacement therapy on linezolid pharmacokinetic/pharmacodynamics: a systematic review.
abstract: BACKGROUND
  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.
  
  
  METHODS
  Citations 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.
  
  
  RESULTS
  Among 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.
  
  
  CONCLUSIONS
  Wide 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.
authors.affiliation: Department of Health Science, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, Florence, 50134, Italy. gianlucavilla1@gmail.com.|Department of Anesthesia and Intensive Car, Azienda Ospedaliero-Universitaria Careggi, Largo Brambilla 3, Florence, 50134, Italy. gianlucavilla1@gmail.com.
authors.forename: Gianluca
authors.initials: G
authors.lastname: Villa
authors.affiliation: Department of Health Science, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, Florence, 50134, Italy.
authors.forename: Paola
authors.initials: P
authors.lastname: Di Maggio
authors.affiliation: Department of Health Science, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, Florence, 50134, Italy.
authors.forename: A Raffaele
authors.initials: AR
authors.lastname: De Gaudio
authors.affiliation: Department of Health Sciences, Section of Clinical Pharmacology and Oncology, University of Florence, Viale Pieraccini 18, Florence, 50139, Italy.
authors.forename: Andrea
authors.initials: A
authors.lastname: Novelli
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, Parma University Medical School, Via Gramsci 14, Parma, 43100, Italy.
authors.forename: Riccardo
authors.initials: R
authors.lastname: Antoniotti
authors.affiliation: Acute and Chronic Renal Failure Unit, Department of Clinical and Experimental Medicine, Parma University Medical School, Via Gramsci 14, Parma, 43100, Italy.
authors.forename: Enrico
authors.initials: E
authors.lastname: Fiaccadori
authors.affiliation: Department of Health Science, Section of Anesthesiology and Intensive Care, University of Florence, Largo Brambilla 3, Florence, 50134, Italy.
authors.forename: Chiara
authors.initials: C
authors.lastname: Adembri
mesh_terms: D058186:Acute Kidney Injury / Q000097:blood* / Q000628:therapy*; D000900:Anti-Bacterial Agents / Q000493:pharmacokinetics* / Q000627:therapeutic use; D016638:Critical Illness / Q000628:therapy*; D006801:Humans; D000069349:Linezolid / Q000493:pharmacokinetics* / Q000627:therapeutic use; D008826:Microbial Sensitivity Tests / Q000639:trends; D064887:Observational Studies as Topic; D011446:Prospective Studies; D017582:Renal Replacement Therapy / Q000639:trends*
chemical_list: D000900:Anti-Bacterial Agents; D000069349:Linezolid
keywords: Acute kidney injury; Adsorption; Clearance; Critical illness; High cut-off membranes; High-flux membranes; Linezolid; Sepsis