AI Article Synopsis
- The study focused on optimizing antibiotic dosing for immunocompromised patients, particularly those with haematological cancers, due to limited data on meropenem pharmacokinetics.
- Researchers created a population pharmacokinetic model based on 88 hospitalized patients and found that kidney function significantly influenced drug clearance.
- The findings recommend administering a high dose of meropenem (6 g/day) via continuous infusion to ensure effective drug levels in these patients.
Article Abstract
Background: Optimal dosing of antibiotics is critical in immunocompromised patients suspected to have an infection. Data on pharmacokinetics (PK) of meropenem in patients with haematological malignancies are scarce.
Objectives: To optimize dosing regimens, we aimed to develop a PK population model for meropenem in this population.
Methods: Patients aged ≥18 years, hospitalized in the haematology department of our 1500 bed university hospital for a malignant haematological disease and who had received at least one dose of meropenem were eligible. Meropenem was quantified by HPLC. PK were described using a non-linear mixed-effect model and external validation performed on a distinct database. Monte Carlo simulations estimated the PTA, depending on renal function, duration of infusion and MIC. Target for free trough concentration was set at >4× MIC.
Results: Overall, 88 patients (181 samples) were included, 66 patients (75%) were in aplasia and median Modification of Diet in Renal Disease (MDRD) CLCR was 117 mL/min/1.73 m2 (range: 35-359). Initial meropenem dosing regimen ranged from 1 g q8h to 2 g q8h over 30 to 60 min. A one-compartment model with first-order elimination adequately described the data. Only MDRD CLCR was found to be significantly associated with CL. Only continuous infusion achieved a PTA of 100% whatever the MIC and MDRD CLCR. Short duration of infusion (<60 min) failed to reach an acceptable PTA, except for bacteria with MIC < 0.25 mg/L in patients with MDRD CLCR below 90 mL/min/1.73 m2.
Conclusions: In patients with malignant haematological diseases, meropenem should be administered at high dose (6 g/day) and on continuous infusion to reach acceptable trough concentrations.
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| http://dx.doi.org/10.1093/jac/dkaa275 | DOI Listing |
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