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 ofmeropenem 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.