Explore Imipenem/Cilastatin two-step dosing compared to 2 hours infusion in patients with severe whether can obtain better results of the pharmacokinetic/pharmacodynamic, for clinical rational use of antimicrobial agents, and provide theoretical support for optimizing dosage regimen.

Compared with Imipenem/Cilastatin 2 hours continuous dosing method and two-step dosing method (0.5 hours before enter half dose, after 1.5 hours, the other half of the input dose) of blood drug concentration in the body than the minimal inhibitory concentrations (MIC) pathogens percent of dosing interval duration (100% fT > MIC), blood drug concentration in the body more than 4 times the minimal inhibitory concentrations (MIC) pathogens percent of dosing interval duration (100% fT > 4 MIC), blood drug concentration peak and the ratio of the minimal inhibitory concentrations (MIC) pathogens (Cmax/MIC), blood drug concentration (Tmax) used in the peak time, used to guide clinical patients with severe infection of Imipenem/Cilastatin usage.

Inclusion Criteria:

• sepsis or severe sepsis or severe infections in the previous 48 hours
• treatment with imipenem/cilastatin (recommended by hospital microbiologists)
• expected duration of hospital stays in the ICU ≥ 72 h from recruitment
• recruited patients agreed to participate in this trial, and had set up a signed informed consent

Exclusion Criteria:

• with an allergy to carbapenems or with an adverse drug reaction to imipenem
• acute or chronic renal failure assessed by serum creatinine concentrations > 280 μmol/L (or creatinine clearance <20mL/min) or those requiring continuous renal replacement therapy
• drug or alcohol abuse
• Pregnant and lactant women
• patients near to death