Ceftazidime Concentration is Correlated to the Glomerular Filtration Rate and Body Mass Index

Launay, Manon; D'Andon, Cornélie Fanton; Correia, Patricia; Hilt, Pauline M.; Thiéry, Guillaume; Perinel-Ragey, Sophie

doi:10.1097/ftd.0000000000001027

Cited by 5 publications

(5 citation statements)

References 5 publications

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“…Increased Vd has already been described in ICU patients, with values around 50-60L, with an average BMI lower than what we observed in this study [8,11]. Surprisingly, weight/BMI were not identi ed as signi cant covariates of the Vd, contrarily to what we expected [4], maybe because nearly 50% patients were obese.…”

Section: Discussioncontrasting

confidence: 77%

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Loading dose of ceftazidime need to be increased in critically ill patients: a retrospective study to evaluate recommended loading dose with pharmacokinetic modeling

Launay,

Ollier,

Kably

et al. 2023

Preprint

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Background In order to rapidly achieve target concentrations and bactericidal efficacy, the administration of a loading dose (LD) is recommended before starting ceftazidime continuous infusion. However, the adequacy of the 2g-LD usually administered should be investigated considering the special pharmacokinetic characteristics of critically ill patients. Materials PK dataset for model development and external validation included patients hospitalized in 6 intensive care units (ICU) in the Saint-Etienne region (France) and in Paris, with ceftazidime continuous infusion and at least one measurement of plasma concentration [IRBN992021/CHUSTE]. Data were analysed with MONOLIX and R softwares. A review of the literature was performed to search for PK models developed in ICU patients, to compare our results with existing models. A simulation of the LD needed to reach a target concentration of 60mg/L was performed with all models. Results Ceftazidime was well described by a one-compartment model with allometrically scaled lognormalized e-glomerular filtration rate as a covariate of clearance, using a dataset of 86 patients/223 samples. Typical ceftazidime clearance and volume of distribution were 4.45L/h and 88L, respectively. The predicted individual ceftazidime concentrations were significantly lower at 24 ± 4hours than at 48 ± 4hours. Of the 8 publications of pharmacokinetics models developed in ICU populations, median volume of distribution was 37.2L. The simulated LD to achieve 60mg/L in 80% of the patients from the models found in the literature was higher than 2g in all but one study. Median LD was 4.9g. Conclusions Standard LD results in delay in achieving target ceftazidime concentration in ICU patients.

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Section: Discussioncontrasting

confidence: 77%

“…We have previously shown that CAZ plasma concentrations correlate with glomerular ltration rate (GFR) and body mass index (BMI) [4], and that obese patients with normal renal function should be administered 7-9g/d by continuous infusion to reach the target range, rather than the usually recommended dose of 6g/d [5].…”

Section: Introductionmentioning

confidence: 99%

Loading dose of ceftazidime need to be increased in critically ill patients: a retrospective study to evaluate recommended loading dose with pharmacokinetic modeling

Launay,

Ollier,

Kably

et al. 2023

Preprint

Self Cite

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“…So far, data on CAZ exposure on obese critically-ill patients were scarce with retrospective observational studies on small cohorts showing 35 to 50% of CAZ underdosing in obese patients (37,38). These patients required signi cantly greater CAZ amount to achieve the target range, which may be explained by higher volume of distribution (27,30) and higher renal clearance (29-31) described in obese and in ICU patients (7,(17)(18)(19)(20)22).…”

Section: Discussionmentioning

confidence: 99%

“…Categorical variables were expressed as number and percentage. Because CAZ concentration correlates to both BMI and GFR (37), univariate correlation analysis was performed between CAZ C/D and GFR in obese and in non-obese patients. Differences were considered signi cant when p < 0.05.…”

Section: Methodsmentioning

confidence: 99%

Towards Optimization of Ceftazidime Dosing in Intensive Care Unit Obese Patients: the end of the “one-size-fits-all” approach?

Correia

Launay

Balluet

et al. 2023

Preprint

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BACKGROUND Ceftazidime (CAZ) is commonly used as pivotal antibiotic against pseudomonas aeruginosa in critically ill patients. ICU patients have severely altered and variable antibiotic pharmacokinetics, resulting in lower antimicrobial concentrations and potentially poor outcome. Several factors, including obesity and renal function, may influence pharmacokinetics. Thus, the objective of the study was to evaluate impact of obesity and renal function on CAZ plasma concentrations and dosing regimen in ICU patients. METHODS All consecutive adult patients from 6 ICUs, treated with continuous CAZ infusion and under Therapeutic Drug Monitoring evaluation were included. Obesity was defined as body mass index ≥ 30 kg/m². Glomerular filtration rate (GFR) was estimated by Chronic Kidney Disease Epidemiology Collaboration formula. CAZ recommended levels for plasma concentrations were between 35 and 80 mg/L. RESULTS A total of 111 patients (45 obese), weighted 90 (±24,4) kg, were included. Mean GFR was 82 mL/min/1,73m2 (±40,3). Recommended CAZ plasma concentrations were achieved only for 49,6% patients, with median dosing regimen of 6g/d. Obese patients had lower CAZ plasma concentrations compared to non-obese patients (37.8 vs 56.3 mg/L; p=0.0042*) despite similar dosing regimens (5.83g/d vs 5.52 g/d, p= 0.2529). Almost all Augmented Renal Clearance patients were underdosed despite CAZ dosing of 6,6g/d (±0,8). Considering weight-based CAZ dosing seemed to attenuate such obesity-related discrepancies, regardless of GFR. CONCLUSIONS ICU obese patients required significantly greater CAZ amount to achieve target range. Tailored dosing regimen may be considered based on weight and GFR. Future prospective studies should be performed to confirm this individualized dosing approach.

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“…We previously demonstrated that ceftazidime concentration is correlated with the glomerular filtration rate and body mass index. 3…”

mentioning

confidence: 99%

Therapeutic Drug Monitoring Consulting Cannot be Ruled out by Model-Informed Precision Dosing

Launay

Correia

Thiéry

et al. 2023

Therapeutic Drug Monitoring

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Ceftazidime Concentration is Correlated to the Glomerular Filtration Rate and Body Mass Index

Cited by 5 publications

References 5 publications

Loading dose of ceftazidime need to be increased in critically ill patients: a retrospective study to evaluate recommended loading dose with pharmacokinetic modeling

Loading dose of ceftazidime need to be increased in critically ill patients: a retrospective study to evaluate recommended loading dose with pharmacokinetic modeling

Towards Optimization of Ceftazidime Dosing in Intensive Care Unit Obese Patients: the end of the “one-size-fits-all” approach?

Therapeutic Drug Monitoring Consulting Cannot be Ruled out by Model-Informed Precision Dosing

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