scholarly journals Elimination of fosfomycin during dialysis with the Genius system in septic patients

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
T. Dimski ◽  
T. Brandenburger ◽  
M. Janczyk ◽  
T. Slowinski ◽  
C. MacKenzie ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Prospective Observational Study ◽  
Kidney Injury ◽  
Serum Levels ◽  
Therapeutic Drug ◽  
Loading Dose ◽  
Dialysis Therapy ◽  
Daily Dialysis ◽  
Wide Variability

AbstractTo assess fosfomycin (FOS) elimination in patients with sepsis and acute kidney injury (AKI) undergoing slow-extended daily dialysis (SLEDD) with the Genius system in a prospective observational study. After ethics committee approval ten patients with sepsis and AKI stage 3 underwent daily SLEDD sessions of eight hours. FOS was applied i.v. at doses of 3 × 5 g per day. FOS serum levels were measured pre- and post hemofilter before, during, and after SLEDD sessions, and instantaneous clearance was calculated. In five of the patients, we analyzed FOS levels after the first dose, in the other five patients serum levels were measured during ongoing therapy. FOS was eliminated rapidly via the hemofilter. FOS clearance decreased from 152 ± 10 mL/min (start of SLEED session) to 43 ± 38 mL/min (end of SLEDD session). In 3/5 first-dose patients after 4–6 h of SLEDD the FOS serum level fell below the EUCAST breakpoint of 32 mg/L for Enterobacterales and Staphylococcus species. In all patients with ongoing fosfomycin therapy serum levels were high and above the breakpoint at all times. FOS toxicity or adverse effects were not observed. FOS serum concentrations exhibit wide variability in critically ill patients with sepsis and AKI. FOS is eliminated rapidly during SLEDD. A loading dose of 5 g is not sufficient to achieve serum levels above the EUCAST breakpoint for common bacteria in all patients, considering that T > MIC > 70% of the dosing interval indicates sufficient plasma levels. We thus recommend a loading dose of 8 g followed by a maintenance dose of 5 g after a SLEDD session in anuric patients. We strongly recommend therapeutic drug monitoring of FOS levels in critically ill patients with AKI and dialysis therapy.

scholarly journals Association between serum levels of interleukin-6 on ICU admission and subsequent outcomes in critically ill patients with acute kidney injury

2019 ◽  
Vol 20 (1) ◽  
Author(s):  
Takashi Shimazui ◽  
Taka-aki Nakada ◽  
Yoshihisa Tateishi ◽  
Taku Oshima ◽  
Tuerxun Aizimu ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Interleukin 6 ◽  
Kidney Injury ◽  
Serum Levels ◽  
Icu Admission

Efficacy and Safety of a Colistin Loading Dose, High-Dose Maintenance Regimen in Critically Ill Patients With Multidrug-Resistant Gram-Negative Pneumonia

2016 ◽  
Vol 32 (8) ◽  
pp. 487-493 ◽  
Author(s):  
Jessica L. Elefritz ◽  
Karri A. Bauer ◽  
Christian Jones ◽  
Julie E. Mangino ◽  
Kyle Porter ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Clinical Cure ◽  
Statistical Significance ◽  
Cohort Analysis ◽  
Kidney Injury ◽  
Multidrug Resistant ◽  
High Dose ◽  
Loading Dose ◽  
Gram Negative

Introduction: Emergence of multidrug-resistant (MDR) gram-negative (GN) pathogens and lack of novel antibiotics have increased the use of colistin, despite unknown optimal dosing. This study aimed to evaluate the safety and efficacy of a colistin loading dose, high-dose (LDHD) maintenance regimen in patients with MDR-GN pneumonia. Methods: A retrospective cohort analysis was performed comparing critically ill patients with MDR-GN pneumonia pre- and postimplementation of a colistin LDHD guideline with a primary outcome of clinical cure. Safety was assessed using incidence of acute kidney injury (AKI) based on RIFLE (risk, injury, failure, loss, end-stage renal disease) criteria. Results: Seventy-two patients met the inclusion criteria (42 preimplementation and 30 postimplementation). Clinical cure was achieved in 23 (55%) patients in the preimplementation group and 20 (67%) patients in the postimplementation group ( P = .31). AKI occurred in 50% of the patients during the preimplementation period and 58% during the postimplementation period ( P = .59) with no difference in initiation rates of renal replacement therapy. Conclusion: The increased clinical cure rate after implementation of the colistin LDHD guideline did not reach statistical significance. The LDHD guideline, however, was not associated with an increased incidence of AKI, despite higher intravenous colistin doses. Opportunity exists to optimize colistin dosage while balancing toxicity, but larger studies are warranted.

Attributable nephrotoxicity of vancomycin in critically ill patients: a marginal structural model study

2020 ◽  
Vol 75 (4) ◽  
pp. 1031-1037 ◽  
Author(s):  
Frederico Carlos de Sousa Arnaud ◽  
Alexandre Braga Libório
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Structural Model ◽  
Trough Level ◽  
Kidney Injury ◽  
Serum Levels ◽  
Marginal Structural Model ◽  
Model Study ◽  
Trough Serum ◽  
Serum Trough

Abstract Background Although vancomycin nephrotoxicity is recognizable, critically ill patients have other potential reasons for acute kidney injury (AKI) and determining its attributable nephrotoxic risk in this population can be cumbersome. Objectives To determine the risk of AKI attributable to vancomycin, controlling for baseline and time-dependent confounders. Methods Time-fixed and daily time-varying variables were extracted from a large public database. The exposures analysed were: (i) IV vancomycin; (ii) serum trough level greater than 15 and 20 mg/L; and (iii) concomitant exposure to vancomycin and piperacillin/tazobactam or other antipseudomonal β-lactams. Censoring and exposure inverse probability of treatment weighting were calculated. Marginal structural models were plotted to evaluate AKI, severe AKI (stage 2/3) and need of renal replacement therapy (RRT). Results A total of 26 865 patients were included; 19.7% received vancomycin during ICU stay. After adjusting for fixed and time-variable confounders, vancomycin exposure was associated with AKI (HR = 1.24, 95% CI = 1.09–1.38), but not with severe AKI or need of RRT (HR = 1.05, 95% CI = 0.91–1.23 and HR = 0.97, 95% CI = 0.74–1.29, respectively). A serum trough level greater than 20 mg/L was associated with AKI (HR = 1.90, 95% CI = 1.52–2.30) and severe AKI (HR = 1.69, 95% CI = 1.31–2.19), but showed no statistically significant association with need of RRT (HR = 1.48, 95% CI = 0.92–2.56). The vancomycin + piperacillin/tazobactam combination was not associated with a greater risk than vancomycin alone. Conclusions The attributable nephrotoxicity of vancomycin in critically ill patients is significantly lower than previously suggested and severe AKI is related to vancomycin only when trough serum levels are greater than 20 mg/L.

scholarly journals Pharmacokinetic Assessment of Vancomycin Loading Dose in Critically Ill Patients

2017 ◽  
Vol 61 (8) ◽  
Author(s):  
Osvaldo Álvarez ◽  
Jose Cristian Plaza-Plaza ◽  
Manuel Ramirez ◽  
Alexis Peralta ◽  
Cristián A. Amador ◽  
...  
Keyword(s):  
Critically Ill ◽  
Critically Ill Patients ◽  
Serum Levels ◽  
The Body ◽  
Critically Ill Patient ◽  
Pharmacokinetic Parameters ◽  
Population Pharmacokinetic ◽  
Loading Dose ◽  
Trough Serum ◽  
Number Of Patients

ABSTRACT The vancomycin loading dose (LD) of 25 to 30 mg/kg is a frequently practiced strategy to achieve effective concentrations from the first-treatment dose. However, considering only the body weight for dosing might be inadequate in critically ill patients due to pharmacokinetics changes. We sought to assess achieving optimal trough serum levels of vancomycin and AUC0–24/MIC in the first 24 h of treatment by using an LD based on population pharmacokinetic parameters of critically ill patients. We performed a concurrent cohort study over 22 months of patients with severe sepsis who received intravenous vancomycin. The patients were treated with three different strategies to initiate vancomycin: without an LD (group A), with an LD of 25 to 30 mg/kg (group B), and with an LD based on population pharmacokinetic parameters of the critically ill patient (group C). An optimal trough serum concentration was achieved in 5, 9, and 83% of patients in groups A, B, and C, respectively. The number of patients that reached optimal AUC0–24 was 2 of 18 (11%), 5 of 11 (46%), and 11 of 12 (92%) in groups A, B, and C, respectively. The statistical analysis for both parameters revealed significant differences in group C with respect to other groups. The administration of the LD calculated from population pharmacokinetic parameters from the beginning of therapy is a more efficient strategy to obtain adequate trough serum concentrations and AUC0–24/MIC in critical patients.

scholarly journals Using Population Pharmacokinetics To Determine Gentamicin Dosing during Extended Daily Diafiltration in Critically Ill Patients with Acute Kidney Injury

2010 ◽  
Vol 54 (9) ◽  
pp. 3635-3640 ◽  
Author(s):  
Jason A. Roberts ◽  
Jonathan Field ◽  
Adam Visser ◽  
Rosemary Whitbread ◽  
Mandy Tallot ◽  
...  
Keyword(s):  
Acute Kidney Injury ◽  
Monte Carlo ◽  
Monte Carlo Simulations ◽  
Critically Ill ◽  
Critically Ill Patients ◽  
Population Pharmacokinetic Model ◽  
Pharmacokinetic Model ◽  
Kidney Injury ◽  
Therapeutic Drug ◽  
Population Pharmacokinetic

ABSTRACT The objective of the present prospective pharmacokinetic study was to describe the variability of plasma gentamicin concentrations in critically ill patients with acute kidney injury (AKI) necessitating extended daily diafiltration (EDD-f) using a population pharmacokinetic model and to subsequently perform Monte Carlo dosing simulations to determine which dose regimen achieves the pharmacodynamic targets the most consistently. We collected data from 28 gentamicin doses in 14 critically ill adult patients with AKI requiring EDD-f and therapeutic gentamicin. Serial plasma samples were collected. A population pharmacokinetic model was used to describe the pharmacokinetics of gentamicin and perform Monte Carlo simulations with doses of between 3 mg/kg of body weight and 7 mg/kg and at various time points before commencement of EDD-f to evaluate the optimal dosing regimen for achieving pharmacodynamic targets. A two-compartment pharmacokinetic model adequately described the gentamicin clearance while patients were on and off EDD-f. The plasma half-life of gentamicin during EDD-f was 13.8 h, whereas it was 153.4 h without EDD-f. Monte Carlo simulations suggest that dosing with 6 mg/kg every 48 h either 30 min or 1 h before the commencement of EDD-f results in 100% attainment of the target maximum concentration drug in plasma (<10 mg/liter) and sufficient attainment of the target area under the concentration-time curve from 0 to 24 h (AUC0-24; 70 to 120 mg·h/liter). None of the simulated dosing regimens satisfactorily achieved the targets of the minimum concentrations of drug in plasma (<1.0 mg/liter) at 24 h. In conclusion, dosing of gentamicin 30 min to 1 h before the commencement of an EDD-f treatment enables attainment of target peak concentrations for maximal therapeutic effect while enhancing drug clearance to minimize toxicity. Redosing in many patients should occur after 48 h, and we recommend the use of therapeutic drug monitoring to guide dosing to optimize achievement of the AUC0-24 targets.

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