Title Pharmacokinetic and Pharmacodynamic Efficacies of Continuous versus Intermittent Administration of Meropenem in Patients with Severe Sepsis and Septic Shock: A Prospective Randomized Pilot Study
Authors Zhao, Hui-Ying
Gu, Jian
Lyu, Jie
Liu, Dan
Wang, Yi-Tong
Liu, Fang
Zhu, Feng-Xue
An, You-Zhong
Affiliation Peking Univ, Peoples Hosp, Dept Crit Care Med, 11 Xizhimen South St, Beijing 100044, Peoples R China.
Peking Univ, Peoples Hosp, Dept Pharm, Beijing 100044, Peoples R China.
Keywords Continuous Infusion
Intermittent Infusion
Meropenem
Pharmacodynamic
Pharmacokinetic
CRITICALLY-ILL PATIENTS
BETA-LACTAM ANTIBIOTICS
CONTINUOUS-INFUSION
INTERNATIONAL GUIDELINES
CONTROLLED-TRIAL
INTENSIVE-CARE
CAMPAIGN
BOLUS
PENETRATION
MANAGEMENT
Issue Date 2017
Publisher Chinese Medical Journal
Citation CHINESE MEDICAL JOURNAL.2017,130(10),1139-1145.
Abstract Background: The antibiotic meropenem is commonly administered in patients with severe sepsis and septic shock. We compared the pharmacokinetic, clinical, and bacteriological efficacies of continuous infusion of meropenem versus intermittent administration in such patients. Methods: Patients admitted to the Intensive Care Unit (ICU) with severe sepsis or septic shock who received meropenem were randomly assigned to either the continuous (n = 25) or intermittent groups (n = 25). The continuous group received a loading dose of 0.5 g of meropenem followed by a continuous infusion of 3 g/day; the intermittent group received an initial dose of 1.5 g followed by 1 g for every 8 h. Clinical success, microbiological eradication, superinfection, ICU mortality, length of ICU stay, and duration of meropenem treatment were assessed. Serial plasma meropenem concentrations for the first and third dosing periods (steady state) were also measured. Results: Clinical success was similar in both the continuous (64%) and intermittent (56%) groups (P = 0.564); the rates of microbiological eradication and superinfection (81.8% vs. 66.7% [P = 0.255] and 4% vs. 16% [P = 0.157], respectively) showed improvement in the continuous group. The duration of meropenem treatment was significantly shorter in the continuous group (7.6 vs. 9.4 days; P = 0.035), where a better steady-state concentration was also achieved. Peak and trough concentrations were significantly different between the continuous and intermittent groups both in the first (Cmax: 19.8 mg/L vs. 51.8 mg/L, P = 0.000; Cmin: 11.2 mg/L vs. 0.5 mg/L, P = 0.000) and third dosing periods (Cmax: 12.5 mg/L vs. 46.4 mg/L, P = 0.000; Cmin: 11.4 mg/L vs. 0.6 mg/L, P = 0.000). For medium-susceptibility pathogens, continuous infusion concentrations above the minimal inhibitory concentration were 100%, which was better than that in the intermittent group. Conclusions: Continuous infusion of meropenem provides significantly shorter treatment duration and a tendency for superior bacteriological efficacy than intermittent administration. Continuous infusion may be more optimal against intermediate-susceptibility pathogens.
URI http://hdl.handle.net/20.500.11897/473464
ISSN 0366-6999
DOI 10.4103/0366-6999.205859
Indexed SCI(E)
Appears in Collections: 人民医院

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