| Background and purpose of studyVancomycin is a glycopeptide antibiotic. Since its discovery in 1958, vancomycin has been used for clinical treatment of severe bacterial infection caused by drug-resistant gram positive bacteria such as methicillin-resistant Staphylococcus Aureus(MRSA). It is a viable option when other common antimicrobial drugs are ineffective. Vancomycin is thus considered to be "the last line of defense" against resistant strains of bacteria.The issues such as its adverse effects and drug resistance have emerged with the applications of vancomycin. In recent years, with the increase number of MRSA related hospital acquired infection, vancomycin treatments and failures are also more frequently heard. Pub Med document search retrieved(Dec, 2015) vancomycin related papers were 23035. For instance, 11410 were about drug resistance, 389 were about renal toxicity, 817 were about dosage regimen, 739 were about consecutive medication, and 1786 were about pharmacokinetics. These results showed that vancomycin is under extensive research and clinical application concerning. Yet, there are still a lot of objectives to be done before a consensus could be reached regarding best method for the vancomycin treatment. This is because the clinical study of vancomycin generated various results. At present, the lack of quantitative study on the clinical application of vancomycin in the northwest region of China is obvious, and this study could help filling this gap and solving the problems from drug administration level. The major topics of our study are the vancomycin efficacy, hepatic and renal toxicity, and pharmacy administration for the critically-ill patients in our hospital. We expect that this study shall provide a theoretical basis for optimization of vancomycin treatment in the northwest China.Materials and methods:1. The retrospective analysis of clinical patient samples: including patient inclusion and exclusion criteria, methods of vancomycin treatment and patient grouping, serum drug concentration, drug efficacy, liver and kidney toxicity and other analytical method.2. Statistical analysis of clinical data with vancomycin therapy: SPSS was used to identify differences between different groups of patients.3. Pharmacokinetic pattern of serum and cerebrospinal fluid drug levels was observed in a critically-ill patient with vancomycin application.4. Pharmacy managing report of vancomycin application: including literature review, comparison analysis, and interviews with clinical doctors.Results: 1. The sample selection and analysis of treatment efficacy in the critically-ill patients with vancomycin therapy in northwest ChinaA total of 125 cases of critically-ill patients in our hospital were selected in this study. Upon informed consent, their information regarding vancomycin regimen, serum drug concentration, and treatment efficacy were recorded. Data demonstrated that among 125 patients, 3 cases were died and 66 cases’ clinical conditions were improved, and 56 cases reached clinical cure. The treatment efficiency reached 97.4% and the clinical cure rate is 44.8%. For two standardized vancomycin therapy protocols(2g/day 2 times daily vs. 1.5g/day 3 times daily), recovery rates of them were 42.1% and 43.8% respectively, and there was no significant difference between them. In all patients with vancomycin application, about 92.2% of cases had serum trough concentrations within the ideal therapeutic range. The 2nd protocol achieved higher rate of ideal therapeutic concentrations. Both vancomycin protocols were effective in treating the critical ill patients.2. The retrospective study of hepatic and renal toxicity in 125 critically-ill patients with vancomycin therapy in northwest ChinaBy the retrospective analysis, we evaluated 125 critically-ill patients with vancomycin therapy in our hospital, which included 35 cases with standardized vancomycin dosing and 90 cases with personalized vancomycin dosing. Potential risk factors of hepatic and renal toxicity were determined for these patients with vancomycin therapy. The results showed that both standard and personalized body weight-based dosing methods of vancomycin had no significant toxicity on hepatic function. Among two standard vancomycin dosing protocols, the 1st vancomycin protocol was related to renal injury, and about 15.6% of patients with body weight-based dosing showed renal injury. Vancomycin doses greater than 38 mg/kg/day(50% vs 11.3%, P=0.004) and serum trough concentration greater than 20 mg/L(57.1% vs 12%, P=0.01) were identified as independent risk factors for vancomycin-associated renal toxicity or nephrotoxicity. We have thus proposed that a regular detection of serum drug concentrations and timely adjustment of drug dosing should be necessary for vancomycin therapy for critically-ill patients.3. A pilot observation on serum and cerebrospinal fluid drug concentrations in a case of critically-ill patient in our hospital who received vancomycin therapyThe blood-brain-barrier(BBB) characterized with selective permeability mechanism has major impact on drug distribution and biological effect in the central nervous system. We chose one case in June 2015 and monitored his serum and cerebrospinal fluid(CSF) drug concentration for 48 h. It showed that during the period of 48 h after vancomycin administration, the minimum serum level was 3.91μg/m L, the maximum serum level was 64.23μg/m L, and average level was 21.56μg/m L. The minimum CSF level was 0.13 μg/m L, the highest CSF level was 3.45μg/m L, and the average level was 1.46μg/m L. In all nine time-points observed, the CSF vancomycin levels were lower than that of serum concentrations. The CSF vancomycin concentration showed a slowly-upward trending. Data indicated that BBB might have great influence on vancomycin distribution in the central nervous system. This case of patient was very difficult to obtain, and it provided valuable original data for further exploration of application of vancomycin for the central nervous system infections.4. A pharmacy managing report and monitoring on the clinical standard administration of vancomycin dosing in our hospitalAccording to “The instruction principle for clinical application of antibiotics”, we worked out the table “Monitoring recording of vancomycin application”. A new document regarding “Announcement on standard clinical application of vancomycin” was completed and carried out in our hospital since August, 2014. We monitored vancomycin therapy process in 620 patients, including vancomycin initial application, usage dosing, detection of serum concentration, adjustment of drug dosing, and outcome of treatment. It indicated that 471 patients(76%, 471/620) reached to a standard level while other 149(24%, 149/620) were not or with abnormal drug responses. These monitoring process or methods showed beneficial on securing standard drug administration and safety for the critically-ill patients with vancomycin therapy in hospital, also suggesting that strict drug monitoring should be still critically important for vancomycin standard therapy.Conclusion: By the retrospective analysis of clinical patients and pharmacy managing process, it showed that vancomycin therapy was reliable for critically-ill patients in northwest China, but there was still risk of renal toxicity. This study has provided new valuable evidence for improving clinical vancomycin therapy quality in our hospital. Our study also suggests that further investigation of standardized dosage regimen, rigorous pharmacy management is still imperative to secure efficacy and safety of the vancomycin therapy. Results of this study exhibit the theoretical and clinical application significance. |
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