DOI: 10.5061/dryad.fxpnvx16s
title: Pharmackinetics/pharmacodynamics of ceftazidime-avibactam in adult critically ill patients receiving continuous renal replacement therapy

description: Ceftazidime-avibactam (CAZ-AVI), a novel antibiotic, is effective in
 treating infections caused by carbapenem-resistant Gram-negative bacteria.
 However, in patients receiving continuous renal replacement therapy
 (CRRT), both the pharmacokinetics(PK) and pharmacodynamics(PD) of the
 drugs can be significantly altered. Currently, there remains a lack of
 clear guidelines regarding optimal dosing regimens for CAZ-AVI during
 CRRT. Prospectively, this study evaluated the PK/PD of CAZ-AVI in 21
 critically ill patients receiving CRRT. We collected blood samples at 5-7
 sampling points within one administration cycle, and then determined the
 total plasma drug concentrations. Phoenix was used to calculate the PK
 parameters. The clearance at steady-state (CLss) of patients receiving
 CRRT was significantly reduced, and drug exposure was also significantly
 increased compared to healthy subjects. Notably, four patients
 demonstrated the free minimum plasma concentrations (fCmin) of CAZ
 exceeding eight times the minimum inhibitory concentration, and 90.48% (19
 cases) of the patients exhibited CAZ plasma concentrations exceeding the
 neurotoxicity threshold of 104 mg/L. PK/PD analysis indicated that the
 standard dosing regimen of 2.5 g every 8 hours of CAZ-AVI may pose a risk
 of excessive drug exposure. In addition, CRRT was the primary elimination
 pathway for CAZ-AVI in critically ill patients with acute kidney injury
 receiving CRRT. Significant differences in extracorporeal clearance were
 observed between continuous venovenous hemodialysis (CVVHD) and continuous
 venovenous hemofiltration (CVVH) for both CAZ and AVI; CVVH demonstrated
 higher clearance for CAZ and AVI compared to CVVHD. To prevent potential
 toxic reactions, it is urgent to establish a safer and more rational
 dosing regimen for patients receiving CRRT.
description: # Pharmackinetics/pharmacodynamics of ceftazidime-avibactam in adult
 critically ill patients receiving continuous renal replacement therapy
 Dataset DOI:
 [10.5061/dryad.fxpnvx16s](https://doi.org/10.5061/dryad.fxpnvx16s) ##
 Description of the data and file structure ``` This dataset contains
 prospective pharmacokinetic and clinical data from 21 critically ill
 patients receiving ceftazidime-avibactam antibiotic therapy while
 undergoing continuous renal replacement therapy (CRRT). The study aimed to
 characterize drug exposure and clearance patterns to inform optimal dosing
 strategies in this complex patient population. Data include serial drug
 concentration measurements, CRRT parameters, microbial susceptibility
 testing, treatment outcomes, and patient characteristics. ``` ### Files
 and variables #### File: Demographic_data.csv **Description:** Demographic
 and clinical characteristics of study participants ##### Variables *
 subjectID:  anonymized subject identifier * age_year: Age category (3
 categories) * sex: Sex code (numeric coding) * weight_kg: Body weight
 category (4 categories) * clinical diagnosis: Primary diagnosis * ALT_U/L:
 Alanine aminotransferase (U/L) * AST_U/L: Aspartate aminotransferase (U/L)
 * HCT: Hematocrit * ALB_g/L: Albumin (g/L) * SCr_umol/L: Serum creatinine
 (μmol/L) * apache score: APACHE II score * SOFA score: SOFA score *
 24-hour Urine Volume_mL: 24-hour urine output(mL) #### File:
 CRRT_parameters_data.csv ##### Variables * subjectID * CRRT modality *
 Ultrafiltration rate_mL/h * total effluent flow rate_mL/kg/h * The
 consecutive days of CRRT treatment_day #### File:
 Ceftazidime_concentration.csv **Description:** Ceftazidime plasma
 concentration measurements ##### Variables * subjectID: Subject identifier
 * Time_h: Time after dose (hours) * Ceftazidime concentration
 pre-filter_mg/L: Pre-filter concentration(mg/L) * Ceftazidime
 concentration post-filter_mg/L: Post-filter concentration(mg/L) #### File:
 Avibactam_concentration.csv **Description:** Avibactam plasma
 concentration measurements ##### Variables * subjectID: Subject identifier
 * Time_h: Time after dose (hours) * Avibactam concentration
 pre-filter_mg/L: Pre-filter concentration(mg/L) * Avibactam concentration
 post-filter_mg/L: Post-filter concentration(mg/L) #### File:
 Medication_Information.csv **Description:** Drug administration details
 ##### Variables * subjectID: Subject identifier * CAZ/AVI dose_g:
 Ceftazidime-avibactam dose(g) * Dosage interval_h: Dosing interval(h) *
 Consecutive days of medication_day: Treatment duration category * method
 of administration: Route of administration * Infusion duration_h: Infusion
 duration category #### File: Microbial_data.csv
 **Description:** Microbiological and treatment outcome data #####
 Variables * subjectID: Subject identifier * Infections site: Infection
 site * Pathogenic microorganisms: Identified pathogens * KB value:
 Kirby-Bauer test results * Susceptibility: Antimicrobial susceptibility *
 Pathogen clearance: Pathogen clearance outcome * Clinical outcome:
 Clinical treatment outcome ## Code/software All can be opened in Excel. ##
 Access information Other publicly accessible locations of the data: * none
 Data was derived from the following sources: * none ## Human subjects data
 I confirm that we received explicit consent from our participants to
 publish the de-identified data in the public domain. We did not disclose
 the personal privacy of the subjects, such as names and ID numbers.
 Instead, we used anonymized subject numbers to represent different
 individual patients.