| Part 1 Study on the etiologic genetic diagnosis of central nervous system infectionsOBJECT:To know the clinical value of genetic method in central nervous system infections.METHODS:The cerebrospinal fluid of patients, who were suspected of central nervous system infection, was collected. The consistency rate between genetic method and traditional method were compared.RESULTS:204 cases of cerebrospinal fluid samples were collected,29 were positive as assessed by culture and 25 were positive as assessed by PCR. Compared with the traditional method, genetic method had a sensitivity of 86.21% and specificity of 100%. If removed 3 samples whose microarray probes were not set, the compliance rate was raised to 99.50%, and the sensitivity was 96.15%. Genetic method detection can help us get the result 3.24±1.22 days before the traditional method detection (P<0.01)CONCLUSION:We can draw the conclusion that genetic diagnostic method had good consistency with traditional method, and detection time was shortened. The new method is reliable and has clinical application value.Part 2 Determination of meropenem in human cerebrospinal fluid and plasma by HPLCOBJECT:To establish a HPLC method for determination of meropenem in human cerebrospinal fluid.METHODS:Chromatorgraphic separation was performed on a TSK-gel 0DS-80TM C18 column. Mobile phase of CSF was ammonium acetate and acetonetrile (90:10, v/v), Mobile phase of Plasma was KH2PO4 and acetonetrile (87:13, v/v). Ultraviolet absorption at 308nm was used for detection. The temperature of column was 35℃.After protein was precipitated by acetonetrile,the derivatized sample was eluted and 20μL injected. Para-aminobenzoic acid (PABA) was used as an internal standard.RESULTS In human cerebrospinal fluid, the retention time of meropenem was 3.810min and the detector response was linear over the concentration range of 0.25-50mg·L-1. The recovery was 94.3-106.3%, and relate standard deviation (RSD) of intra-day and inter-day assays were all less than 5%. In human plasma, the retention time of meropenem was 3.148min and the detector response was linear over the concentration range of 0.5-100mg·L-(?)The recovery was 82.6-96.6%, and relate standard deviation (RSD) of intra-day and inter-day assays were all less than 10%. CSF and plasma stored at-80℃for six months at various concentrations in cerebrospinal fluid, meropenem did not reveal any appreciable degradation.CONCLUSION The method is simple, sensitive and accurate, and can be used for the pharmacokinetic study.Part 3 PK/PD of meropenem in central nervous system infectionsOBJECT:To explore the PK/PD of meropenem in Central Nervous System Infections.Thus we can optimize the treatment of meropenem.METHODS:Neurosurgical patients, who were treated by meropenem, were selected based on inclusion criteria and exclusion. We collected blood and CSF samples on schedule, and got drug concentration by HPLC. At the same time, we collected their clinical data. Then we calculated PK/PD data, and determined the optimal dosage regimen.RESULTS:The dosage group which was received 2g(q8h) of meropenem has a maximum value of %T>MIC and Cmax/MIC, and also has the best blood-brain barrier penetration. For Acinetobacter baumannii, when MIC<0.5mg/L, the plasma concentrations and CSF concentration of three groups were higher than MIC in the dosing interval (%T>MIC was 100%).When MIC<2mg/L, the value of %T>MIC(both in the plasma and csf)was more than 50%. If MIC2mg/L, the value of %T>MIC (csf) was not ideal. When the MIC value is less than 4mg/L, the Cmax>MIC (plasma) in more than 5 times. But only in 2g q8h dosage group, the Cmax>MIC(CSF) is 5 times when MIC.25mg/L.CONCLUSION:To cure Central Nervous System Gram-negative Bacterial Infections,2g q8h dosage regimen is the best, followed by 1g q6h, 1g q8h. removing the drainage system would be useful of pathogen removal. |
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