Yuyi Zhang1, Jing Zhang2, Yuancheng Chen2, Jicheng Yu2, Guoying Cao2, Xiaojie Wu2, Mingyu Chen3, Jufang Wu4, Xu Zhao2. 1. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; Shanghai Public Health Clinical Center, Fudan University, Shanghai, China. 2. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China. 3. Department of Neurosurgery, Huashan Hospital, Fudan University, Shanghai, China. 4. Institute of Antibiotics, Huashan Hospital, Fudan University, Shanghai, China; China Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China. Electronic address: 13816357099@163.com.
Abstract
OBJECTIVE:Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration. METHODS: A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem. RESULTS: The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively. CONCLUSIONS: Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens.
RCT Entities:
OBJECTIVE:Meropenem is important for management of postneurosurgical meningitis, but the data about its penetration into cerebrospinal fluid (CSF) are inadequate. This prospective, open-label study investigated the pharmacokinetic profile of meropenem in patients with postneurosurgical meningitis, especially its CSF penetration. METHODS: A total of 82 patients with postneurosurgical meningitis were included to receive meropenem intravenously according to a regimen of 2 g every 8 hours, 1 g every 8 hours, or 1 g every 6 hours. After infusion of 4 doses, blood and CSF samples were collected simultaneously at predefined time points. The high-performance liquid chromatography ultraviolet method was used to determine the concentration of meropenem. RESULTS: The peak meropenem concentration in blood and CSF was 43.2 ± 5.3 and 2.4 ± 0.3 mg/L in the group who received 2 g every 8 hours; 28.9 ± 2.7 and 1.2 ± 0.2 mg/L in the group who received 1g every 8 hours; and31.5 ± 3.4 and 1.6 ± 0.2 mg/L in the group who received 1g every 6 hours. The maximal percent penetration into CSF was 17.6% ± 7.3%, 14.3% ± 1.7%, and 30.9% ± 24.2%, respectively. CONCLUSIONS: Dosing regimens of meropenem 1 g every 6 hours and 2 g every 8 hours provided higher CSF penetration than 1 g every 8 hours. A higher dose and shorter dosing interval of meropenem may be more useful for clearance of pathogens.
Authors: Mohammad H Alshaer; Brooke Barlow; Nicole Maranchick; Miriam Moser; Leon Gramss; Heinz Burgmann; Valentin Al Jalali; Michael Wölfl-Duchek; Walter Jäger; Stefan Poschner; Walter Plöchl; Andrea Reinprecht; Karl Rössler; Andreas Gruber; Markus Zeitlinger; Charles A Peloquin; Arthur Hosmann Journal: Antimicrob Agents Chemother Date: 2022-07-14 Impact factor: 5.938