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Our aims were to (i) characterize meropenem PPK in plasma and CSF and (ii) recommend favorable dosing regimens in postneurosurgical meningitis patients. Eighty-two patients were enrolled to receive meropenem infusions of 2 g every 8 h (q8h), 1 g q8h, or 1 g q6h for at least 3 days. Serial blood and CSF samples were collected, and concentrations were determined and analyzed via population modeling. Probabilities of target attainment (PTA) were predicted via Monte Carlo simulations, using the target of unbound meropenem concentrations above the MICs for at least 40% of dosing intervals in plasma and at least of 50% or 100% of dosing intervals in CSF. A two-compartment model plus another CSF compartment best described the data. The central, intercentral\/peripheral, and intercentral\/CSF compartment clearances were 22.2 liters\/h, 1.79 liters\/h, and 0.01 liter\/h, respectively. Distribution volumes of the central and peripheral compartments were 17.9 liters and 3.84 liters, respectively. The CSF compartment volume was fixed at 0.13 liter, with its clearance calculated by the observed drainage amount. The multiplier for the transfer from the central to the CSF compartment was 0.172. Simulation results show that the PTAs increase as infusion is prolonged and as the daily CSF drainage volume decreases. A 4-hour infusion of 2 g q8h with CSF drainage of less than 150 ml\/day, which provides a PTA of &gt;90% for MICs of \u22648 mg\/liter in blood and of \u22640.5 mg\/liter or 0.25 mg\/liter in CSF, is recommended. (This study has been registered at ClinicalTrials.gov under identifier NCT02506686.)<\/jats:p>","DOI":"10.1128\/aac.00997-16","type":"journal-article","created":{"date-parts":[[2016,8,30]],"date-time":"2016-08-30T02:03:38Z","timestamp":1472522618000},"page":"6619-6625","update-policy":"https:\/\/doi.org\/10.1128\/asmj-crossmark-policy-page","source":"Crossref","is-referenced-by-count":43,"title":["Population Pharmacokinetics and Dosing Regimen Optimization of Meropenem in Cerebrospinal Fluid and Plasma in Patients with Meningitis after Neurosurgery"],"prefix":"10.1128","volume":"60","author":[{"given":"Cheng","family":"Lu","sequence":"first","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuyi","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mingyu","family":"Chen","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ping","family":"Zhong","sequence":"additional","affiliation":[{"name":"Department of Neurosurgery, Huashan Hospital Affiliated to Fudan University, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yuancheng","family":"Chen","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jicheng","family":"Yu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaojie","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jufang","family":"Wu","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jing","family":"Zhang","sequence":"additional","affiliation":[{"name":"Institute of Antibiotics, Huashan Hospital Affiliated to Fudan University, Shanghai, China"},{"name":"Key Laboratory of Clinical Pharmacology of Antibiotics, Ministry of Health, Shanghai, China"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"235","reference":[{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ajic.2004.10.001"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1227\/01.NEU.0000345645.51847.61"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra0804573"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1086\/518580"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1016\/S1130-1473(09)70175-7"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.ijantimicag.2011.10.004"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.3844\/ajidsp.2009.21.25"},{"key":"e_1_3_2_9_2","first-page":"365","article-title":"Clinical analysis of 45 cases of intracranial infection after neurosurgery","volume":"12","author":"Chen MY","year":"2012","unstructured":"Chen MY, Zhong P, Wu JF, Xu J, Xu M, Chen DQ, Huang X. 2012. 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