Meropenem Target Attainment and Population Pharmacokinetics in Critically Ill Septic Patients with Preserved or Increased Renal Function

Abstract

Purpose Critically ill patients with preserved or increased renal function have been shown to be at risk of underexposure to meropenem. Although many meropenem population pharmacokinetic (PK) models have been published, there is no large prospective population PK study with rich sampling focusing on patients most at risk of suboptimal pharmacokinetic/pharmacodynamic (PK/PD) target attainment. Therefore, the aim of the present study was to evaluate PK/PD target attainment and to perform a thorough covariate screening using population PK modelling of meropenem in septic patients with preserved or increased renal function. Patients and Methods A single-centre prospective observational PK study was performed in the intensive care unit (ICU) of the University Hospitals Leuven. Patients with severe sepsis or septic shock and treated with meropenem in the ICU were screened for inclusion. Patients were excluded if they received renal replacement therapy or had an estimated glomerular filtration rate according to the Chronic Kidney Disease Epidemiology collaboration equation <70 mL/min/1.73m 2 on the day of PK sampling. Successful PK/PD target attainment was defined as an unbound meropenem trough concentration above 2 mg/L or 8 mg/L. Population PK modelling was performed with NONMEM7.4. Results In total, 58 patients were included, contributing 345 plasma samples over 70 dosing intervals. The 2 mg/L and 8 mg/L targets were successfully attained in 46% and 11% of all dosing intervals, respectively. A two-compartment population PK model with linear elimination and interindividual variability on clearance best described meropenem PK. The estimated creatinine clearance according to the Cockcroft-Gault equation was the only covariate retained during population PK analysis. Conclusion This study provided detailed insight into meropenem PK in critically ill patients with preserved or increased renal function. We observed poor PK/PD target attainment, for which renal function was the only significant covariate. Trial Registration This study is registered at ClinicalTrials.gov (NCT03560557).

Meropenem pharmacokinetic/pharmacodynamic target attainment and clinical response in ICU patients: A prospective observational study

“…Studies with population PK modeling reports variable results and lower meropenem PK/PD TAs for ICU patients than in the present study 5,6,25,26 . Furthermore, in many PK/PD modeling studies with dose simulations and dose recommendations, the clinical endpoints are missing 5–7 .…”

“…24 Studies with population PK modeling reports variable results and lower meropenem PK/PD TAs for ICU patients than in the present study. 5,6,25,26 Furthermore, in many PK/PD modeling studies with dose simulations and dose recommendations, the clinical endpoints are missing. [5][6][7] The high pharmacokinetic variability observed in the present population did not support the progress to dosing simulations from PK modeling.…”

Population Pharmacokinetic Model and Dosing Simulation of Meropenem Using Measured Creatinine Clearance for Patients with Sepsis

“… 8 , 9 The PPK parameters in this study were similar to those previously reported for patients with sepsis. 15 As CG-CCr is estimated using factors such as age, weight, and SCr, it is markedly affected by these factors. Arulkumaran et al 16 reported that SCr values in patients with sepsis were elevated in the first 3 hours, normalized after 12 hours owing to fluid resuscitation, and increased after 24 hours.…”

Kajian Penggunaan Antibiotik Pada Pasien Covid-19 Dengan Pneumonia Di Ruang Perawatan Intensif Rumah Sakit H.S Samsoeri Mertojoso

“…Hal ini disebabkan kreatinin klirens pasien ditemukan sebesar 41,17 mL/menit sehingga membutuhkan penyesuaian interval menjadi 12 jam. Meropenem dengan serum kreatinin 26 -50 mL/menit membutuhkan penyesuaian dosis 0,5 -1 g IV setiap 12 jam (Gijsen et al, 2022) Berdasarkan hasil penelitian, dari 21 pasien COVID-19 dengan pneumonia dengan status keluar rumah sakit (KRS) sembuh didapatkan rentang lama pemberian antibiotik seperti pada tabel 6. Antibiotik pada penelitian ini diberikan tidak lebih dari 14 hari.…”