Study Of Mutant Prevention Of Colistin Combined With Levofloxacin Against MDR-AB

Part1Study of Mutant Prevention of Colistin combined with Levofloxacin against MDR-ABObjective:(1) To acquire MICs of ten antibiotics against MDR Acinetobacter baumannii isolated in recent years;(2) To select and class bacterial genotypes by PFGE;(3) Based on the theory of MSW, MPCs was to be measured and analysed of the strains;(4) To set up a method to meet the determination of colistin and levofloxacin in MHB;(5) To analyse the value of the colistin combined with levofloxacin against A baumannii through a PK/PD model.Methods:(1) MICs were measured by agar plate and broth dilution method;(2) The genetic homology of the clinical isolates was determined by pulsed-field gel electrophoresis (PFGE);(3) The MICs of colistin combined with other drugs were measured through the checkerboard dilution method, and then MPCs were measured based on that;(4) MHB were treated through SPE and the density of colistin and levofloxacin were simultaneously determinated by HPLC-MS/MS;(5) The PK/PD model was constructed mainly by peristaltic pump and we made an analysis by colony count and MICs of strains obtained during the test.Results:The73multi-drug resistant Acinetobacter baumannii (MDRAB) were confirmed and27.4%of which were pan-drug resistant strains. Of high resistance ratio of A. Baumannii, it included cephalosporins, carbapenems, fluoroquinolones, aminoglycosides and beta lactam enzyme inhibitor compound preparation. However, there was only one strain exhibit resistant to colistin. The resistance rate of levofloxacin decreased from90.3%in2007to36.5%. All of the strains were classified to6PFGE colonytypes and strains belong to D type were high sensitive to levofloxacin. When colistin was treated combined with levofloxacin, the fractional inhibitory concentration (FIC) of AB19was lower than0.5. The FIC index of AB34 and AB42were0.6and0.75, which were close to0.5. The select index (SI) descended4-8fold in the MPC after combination compared with which in monotherapy. The HPLC-MS/MS method showed that within-day accuracy was86.10%-l11.05%, day to day accuracy was85.97%-115.70%, within-day accuracy precision (RSD)=6.83%and day to day precision (RSD)=9.85%. The PK/PD model produced a target colistin half-life of4h, and loading does was4.5μg/mL. The quantity measured reached the lowest in the first half-life time. The amount in colistin monotherapy group descended below10~7. In AB19group, after treatment of colistin combined with levofloxacin, the volume decreased1-2log10CFU/mL compared with colistin monotherapy. However, there was no significant difference between group AB34and AB42about colony count. During that strains selected in group AB19showed a phenomenon that MIC rose after48h when treatment of colistin monotherapy, which was different with combination group. We could see a similar situation existed in group AB42.Conclusion:The study showed the high sensitive ratio of colistin against A. baumannii and its fast acting. The resistant ratio of levofloxacin decreased against A. baumannii isolated in recent years at this area. This test showed that synergism emerged when treatment of colistin combined with levofloxacin and the combination enhanced their mutant prevention ability in some way. Moreover, the study in vitro suggested strongly developing new therapeutic strategies in treatment. The data in the test as basis provided valuable reference in further study and clinical application. Part2Clinical Pharmacy PracticeObjective:To understand and grasp technical skills and ability in clinical pharmacy and to promote proper use of clinical medications through the practice in the field. To research the focus issues by literature metrology. To master methods commonly used in TDM. To study clinical trial and get to familiar with the laws and regulations and SOP required in GCP.Methods:Participating in clinical consultation work, and to do some research in the clinical focus issues by literature metrology and bibliography retrieval technology. Treatment drug monitoring was to work through HPLC, TDX, ELISA, et al. Participating in training and clinical trial, and passing some test of GCP held by SFDA.Results:Several problems were solved in clinical treatment through application of clinical pharmacy technology and the effect of meropenem on valproic acid was confirmed. We have got methods commonly used in TDM in practice and built new assay method of concentration about cefdinir and cefuroxime in plasma. Through participating in clinical trial and the training of GCP, I got the point in flowsheet.Conclusion:The practice connected the theory or knowledge accepted in class with application in daily job, which was a substantial basis to a clinical pharmacist.