| Over the past few decades, antimicrobial agents have been widely used, which makes bacterial resistance developed gradually. And the new data shows that, in the natural environment bacterials can not only compete with each other, but can also transduct important signals. The infection of Pseudomonas aeruginosa(PA) is particularly worried, because it has the strong genetic plasticity(adaptability and variability), and can obtain additional resistance genes to enrich the genome by horizontally transmitting them, and then get the resistant to known antimicrobial agents,finally makes the clinical treatment as a result of failure or even death. Therefore,optimizing the treatment of PA infection is quite important. At present, beta-lactam antibiotics are the main drugs against PA, but it is not enough optimized to treat PA infection with known beta-lactam antibiotics in the clinical setting. The study aims at investigating the effect of different dosing regimens on the clinical efficacy, by collecting clinical indicators and the dosing regimen information of PA infection patients,evaluating the availability of the optimization, increasing the clearance of beta-lactam antibiotics against PA, controlling the infection effectively, and promoting the significant role of clinical pharmacists.This paper is divided into three parts:The first part: A retrospective analysis: Explored the effect of different beta-lactam drug regimens on the clinical efficacy against Pseudomonas aeruginosaObjective:Retrospectively analyzed the anti-infection treatment course, the changing times of dosing regimens and the cost of the treatment, etc., the study explored the effect of different beta-lactam drug regimens on the clinical efficacy against Pseudomonas aeruginosa, provided the scientific basis to the rational use of beta-lactam drugs in the clinical setting.Methods:1. Collection of casesCollected the information of PA infection patients who were treated with beta-lactam drugs in the initial treatment regimen from January 2013 to December 2013,and conducted the retrospective analysis. The information includes the situation of anti-infection drug administration(the anti-infection treatment course, the changing times of dosing regimens and the combination therapy conducted or not) and the cost of the treatment dosing regimens.2. Statistical method Applied Excel 2010 to establish the database, statistically analyzed the database by using SPSS 20.0 statistical software. Quantitative data consistent with normality and homogeneity of variance analyzed by using t test; Quantitative data which were normal distributive but variable, and which were not consistent with normality, were analyzed by using the rank sum test; Qualitative data used χ2 test or fisher exact probability method,P<0.05 was expected to be statistically significant.Results:A total of 74 cases met the inclusion criteria, including ICU 13 cases(17.6%),respiratory department of internal medicine 31 cases(41.8%), blood department of internal medicine 30 cases(40.5%). The number of cases with Beta-lactam drug for ≤2times / day and ≥ 3 times / day were 33 cases(44.6%) and 41(55.4%), respectively. The course of the treatment were 14.6 ± 10.7 days and 9.1 ± 6.8 days, this difference between two groups has statistical significance(t=2.582, P < 0.05). The changing times of dosing regimens during the treatment process are 2.8 ± 2.4 times and 1.5 ± 1.5 times, the difference between two groups has statistical significance(t=2.583, P < 0.05). The costs of the anti-infection treatment are 5840.6±7952.2 dollars and 5754.8 of ±5571.2 dollars.The average periods of treatment with monotherapy and combination therapy are 12±10.2 days and 11.4 ± 8.6 days. There was no significant difference between two groups(t=0.255, P>0.05).The second part: Prospective study on the intervention of the dosing regimen for PA infectionObjective:Based on results from the retrospective analysis,the study conducted the intervention of the dosing regimen for PA infection with Beta-lactam antibiotics in clinical setting, and then statistically analyzed the anti-infection treatment course, the changing times of dosing regimens and the monitoring of laboratory indicators and the cost of anti-infection treatment, etc., explored the effect of different beta-lactam drug regimens on the clinical efficacy against Pseudomonas aeruginosa, provided the scientific basis to the rational use of beta-lactam drugs in the clinical setting.Methods:1. Collection and grouping of casesObject people in the study were patients who treated the Pseudomonas aeruginosa infection in a hospital from July 2015 to January 2016, and also met the entry criteria of the research. Determined whether conducted the intervention or not based on whether the initial drug administration was optimized, the successful intervention and the optimized cases were classified as the experimental group, the failing intervention as the control group. Collected the anti-infection treatment course, the changing times of dosing regimens, the cost of anti-infection treatment, the change of signs in patients before and after the treatment and the occurrence of drug-related adverse reactions, the blood examination before and after 3 days, 7 days of the treatment, the specimen condition of the Initial treatment and 7 days after the treatment, etc.2. Statistical methodApplied Excel 2010 to establish the database, statistically analyzed the database by using SPSS 20.0 statistical software. Quantitative data consistent with normality and homogeneity of variance analyzed by using t test; Quantitative data which were normal distributive but variable, and which were not consistent with normality, were analyzed by using the rank sum test; Qualitative data used χ2 test or fisher exact probability method,P<0.05 was expected to be statistically significant.Results:Among 97 patients in the research, the experimental group and the control group were 49 cases(50.5%) and 48 cases(49.5%), the course of the anti-infection treatment were 9.90±5.22 days and 12.79±7.47 days, the length of stay in hospital were 21.06±8.71 days and 28.54±16.37 days. The difference between two groups was statistically significant(P<0.05). The recovery times of the body temperature in two groups were4.09 ± 3.94 days and 6.93±3.13 days, respectively. Compared with the initial treatment,the indexes of WBC in laboratory after 7 days of treatment were decreased 5.48 ±11.06(×109/L) and 0.07 ±2.56(×109/L), NEUT decreased 7.28 ±7.71% and 1.18 ±8.34%,P=0.000<0.05, all Ps were below 0.05, it can be shown that the difference between two groups was statistically significant.The third part: Evaluation of the drug administration in PA infection patients with Beta lactam antibiotics by using the PK/PD principleObjective:Validated and evaluated f%T>MIC of different drug administrations by using the PK/PD principle.Methods:1. Determination of MICDetermined MIC values of Pseudomonas aeruginosa strains isolated from second patients by the agar dilution method. Pharmacokinetic data were collected from the published study in healthy volunteers. The pharmacokinetic parameters including t1/2(half-life), Vd(apparent volume of distribution) and fu(drug unbound fraction) were expressed by mean ± standard deviation. Calculated f%T >MIC by the formulation, and then compared the result.2. Determination of the standard valueCalculated the standard rate of f%T>MIC based on the target index of carbapenem antibiotics greater than or equal to 40%, the target index of other beta-lactam antibiotics greater than or equal to 50%.3. Statistical methodApplied Excel 2010 to establish the database, statistically analyzed the database by using SPSS 20.0 statistical software. Quantitative data consistent with normality and homogeneity of variance analyzed by using t test; Quantitative data which were normal distributive but variable, and which were not consistent with normality, were analyzed by using the rank sum test, P<0.05 was expected to be statistically significant.Results:The results of f%T>MIC in groups with Beta-lactam drug for ≥ 3 times / day and ≤2times / day were 95.81 ± 57.49% and 44.36 ± 22.10%, respectively. The difference was statistically significant(P < 0.05); the standard rate was 79.6% and 31.3%, compared with each other, the group with Beta-lactam drug for ≥ 3 times / day has obvious advantages.Conclusion:1. This study suggested that the treatment of the PA infection is not enough optimized.2. The treatment with Beta-lactam drug for ≥ 3 times / day was superior to the regimen for ≤2 times / day in the clinical setting, because of its advantage in the anti-infection effect, it’s obviously improved f%T>MIC and its higher standard rate.3. Timely and early intervention of cases with un-optimized drug regimen against PA by clinical pharmacists can significantly improve the clinical efficacy of beta-lactam antibiotics, and fully play the initiative of clinical pharmacists. |
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