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The effect of a loading dose of meropenem on outcomes of patients with sepsis treated by continuous renal
Sui-Qing Ni1, Wen-Bing Teng1, Yong-Hong Fu2
1Department of Pharmacy, Guangzhou First People's Hospital, School of Medicine, South China University of Technology, Guangzhou, 510180, Guangdong, China.
Background:
Sepsis and continuous renal replacement therapy (CRRT) are both responsible for the alterations of the pharmacokinetics of antibiotics. For patients with sepsis receiving CRRT, the serum concentrations of meropenem in the early phase (< 48 h) was significantly lower than that in the late phase (> 48 h). This current trial aimed to investigate whether administration of a loading dose of meropenem results in a more likely achievement of the pharmacokinetic (PK)/pharmacodynamics (PD) target (100% fT > 4 × MIC) and better therapeutic results in the patients with sepsis receiving CRRT.
Methods:
This is a single-blinded, single-center, randomized, controlled, two-arm, and parallel-group trial. This trial will be carried out in Guangzhou First People's Hospital, School of Medicine, South China University of Technology Guangdong, China. Adult patients (age ≥ 18 years) with critical sepsis or sepsis-related shock receiving CRRT will be included in the study. The subjects will be assigned to the control group and the intervention group (LD group) randomly at a 1:1 ratio, the estimated sample size should be 120 subjects in each group. In the LD group, the patient will receive a loading dose of 1.5-g meropenem resolved in 30-ml saline which is given via central line for 30 min. Afterward, 0.75-g meropenem will be given immediately for 30 min every 8 h. In the control group, the patient will receive 0.75-g meropenem for 30 min every 8 h. The primary objective is the probabilities of PK/PD target (100% fT > 4 × MIC) achieved in the septic patients who receive CRRT in the first 48 h. Secondary objectives include clinical cure rate, bacterial clearance rate, sepsis-related mortality and all-cause mortality, the total dose of meropenem, duration of meropenem treatment, duration of CRRT, Sequential Organ Failure Assessment (SOFA), C-reactive protein levels, procalcitonin levels, white blood cell count, and safety.
Discussion:
This trial will assess for the first time whether administration of a loading dose of meropenem results in a more likely achievement of the PK/PD target and better therapeutic results in the patients with sepsis receiving CRRT. Since CRRT is an important therapeutic strategy for sepsis patients with hemodynamic instability, the results from this trial may help to provide evidence-based therapy for septic patients receiving CRRT.
Trial Registration:
Chinese Clinical Trials Registry, ChiCTR2000032865 . Registered on 13 May 2020, http://www.chictr.org.cn/showproj.aspx?proj=53616 .
Insights
Administering a meropenem loading dose to sepsis patients on continuous renal replacement therapy (CRRT) may improve antibiotic effectiveness. This study investigates if a loading dose achieves pharmacokinetic/pharmacodynamic targets and enhances therapeutic outcomes in these critically ill patients.
Area of Science:
- Critical care medicine
- Pharmacology
- Nephrology
Background:
- Sepsis and continuous renal replacement therapy (CRRT) alter antibiotic pharmacokinetics.
- Meropenem serum concentrations are lower in the early phase of CRRT in sepsis patients.
- Optimizing meropenem dosing is crucial for effective sepsis treatment during CRRT.
Purpose of the Study:
- To evaluate if a meropenem loading dose improves achievement of pharmacokinetic/pharmacodynamic (PK/PD) targets in sepsis patients receiving CRRT.
- To assess the impact of a meropenem loading dose on therapeutic outcomes, including clinical cure and mortality.
- To provide evidence-based meropenem dosing strategies for sepsis patients undergoing CRRT.
Main Methods:
- Single-center, randomized controlled trial with two parallel arms (loading dose vs. standard dose).
- Inclusion of adult patients with critical sepsis or septic shock requiring CRRT.
- Primary endpoint: probability of achieving 100% time above 4x MIC (fT>4xMIC) within 48 hours.
Main Results:
- The study is designed to assess the PK/PD target achievement and therapeutic results.
- Secondary objectives include evaluating clinical cure rates, bacterial clearance, and mortality.
- Safety and impact on organ function (SOFA score) will also be monitored.
Conclusions:
- This trial will be the first to examine the efficacy of a meropenem loading dose in sepsis patients on CRRT.
- Results may inform optimized, evidence-based meropenem therapy for this vulnerable patient population.
- Improved PK/PD target attainment could lead to better clinical outcomes in septic patients requiring CRRT.
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