Objective To study the distribution and concentration of meropenem in rabbit bile. Methods The rabbits were cannulated with a silicone tube in the common bile duct and the blank bile was collected. The rabbits were then administered intravenously with meropenem. Multiple bile samples (1.5 ml) were collected at different phases after the administrations. According to requirement of the high performance liquid chromatography (HPLC), the specificity test was undertook. The blank bile was then mixed with meropenem and mobile phase, respectively, in order to obtain a series of bile samples at different concentrations ranging from 0.5 to 500 μg/ml. The samples were analyzed with HPLC and the chromatographic peak area of meropenem contents were quantitated through external reference method. The linear regression equation was used to analyzed the relationship between the drug concentrations and the chromatographic peak areas. The bile samples that were collected after drug administrations were pretreated and the chromatographic peak areas were assayed by the liquid chromatograph. The bile concentrations were then calculated according to the regression equation, and the concentration-time distribution of meropenem in the bile was obtained ultimately. Results The specificity test indicated the bile dopant peak and the meropenem chromatographic peak were well-separated under chromatographic condition of the mobile phase. The standard curve regression equation was S=2 209.10C-1 251.34, r=0.999 9, and minimum quantitation limit of meropenem was 0.5 μg/ml. After a single i.v. administration of 75 mg/kg of meropenem in each rabbit, drug concentrations reached (38.36±14.17) μg/ml immediately in bile， which significantly exceeded the minimum inhibitory concentrations (MIC90) for most gram negatives, which range from 0.031 to 2 μg/ml. The bile concentration of meropenem decreased quickly over time, and meropenem was eliminated completely in rabbit bile 3 hours after intravenous injection. Conclusion Meropenem could achieve adequate bile concentration for the treatment of biliary tract infection due to susceptible bacteria. However, because of its rapid biliary elimination, meropenem should be used in shorter interval time.
ObjectiveTo systematically review the efficacy and safety of extended or continuous intravenous infusion (EI/CI) versus short-term intravenous infusion (STI) of imipenem/meropenem in adult patients with severe lung infection. MethodsWe electronically searched databases including PubMed, EMbase, The Cochrane Library (Issue 6, 2015) and CBM from inception to June, 2015, to collect random controlled trials (RCTs) about EI/CI versus STI of imipenem/meropenem for severe infection. Two reviewers independently screened literature, extracted data and assessed the risk of bias of included studies. Then, meta-analysis was performed using RevMan 5.2 software. ResultsA total of 6 RCTs involving 442 patients were included. The results of meta-analysis showed that, compared with the STI group, the EI/CI could significantly improve the microbiological success rate (RR=1.16, 95%CI 1.02 to 1.32, P=0.02) without increasing adverse drug reaction (RR=0.99, 95%CI 0.65 to 1.52, P=0.97). There were no significant differences in clinical effective rate (RR=1.12, 95%CI 0.97 to 1.28, P=0.13), survival rate (RR=1.03, 95%CI 0.92 to 1.16, P=0.62) and hospital stays (MD=-0.43, 95%CI-1.29 to 0.42, P=0.32) between the two groups. Conclusions There is no significant difference in clinical effect between EI/CI and STI for severe lung infection. While, the infections caused by gram-negative bacteria with high MIC could benefit more from EI/CI. Due to the limited quantity and quality of the included studies, the above conclusion still need to be further verified by more high quality studies.