| Objective:To investigate whether antimicrobial agents dosing in severe sepsis patients achieve therapeutic drug concentration based on PK/PD theory and provide reference for individualized medication.Methods:1、39 cases of patients with severe sepsis administered tigecycline intravenous infusion were analyzed to high and low dose group:low-dose group (50 mg ql2h) and high-dose group (100 mg ql2h). The blood samples were taken from patients after the 7th dosage immediately, after administration 6h and before the next administration; and plasma concentrations were determined by HPLC. Then the AUIC standard rate of patients was calculated according to the minimum inhibitory concentration (MIC) value and clinical efficacy and bacterial eradication rates. Linear regression was used to describe the effect of relevant year, sex, APACHE Ⅱ, serum creatinine, dosage and albumin on tigecycline AUC. And the affection on AUIC and bacterial clearance, clinical prognosis was investigated.2, This was a retrospectively analysis about 20 severe sepsis with acute kidney injury patients with meropenem intravenous infusion. The patients were grouped by the level of the APACHEⅡ score and APACHE Ⅱ is less than or equal to 25 for mild group, while APACHEⅡ>25 for severe group. The blood samples were taken from each patient before the fourth dosage and it was determined by high performance liquid chromatography (HPLC). Then the standard rate of 100%T>MIC and 100%T>4 x MIC was calculated when the minimum inhibitory concentration (MIC) value were different. Regression was peformed to explore the effect of relevant APACHE II, albumin, creatinine clearance rate and clinical outcome on meropenem serum trough concentration.Results:1、In this study,39 patients with 50 cases tigecycline AUIC,21 cases (53.85%) meet the target range (abdominal infections AUIC≥6.96, lung infection AUIC≥12.8, skin and soft tissue infections≥>17.9). Low-dose group, high dose group the overall compliance rate of 47.62%and 61.11%, respectively, the low-dose group lungs, abdominal infections compliance rate of 36.36%, 60%, respectively; high dose group lungs, abdominal, skin and soft tissue infections standards rates were 71.43%,66.67% and 50%, respectively. When the clinical MIC values were 0.5,1.0,2.0,3.0,8.0μg/ml, the PK/PD compliance rate target for the low dose group were 100%、 80%、50%、0%、0% while high dose group were 100%、80%、100%、25%、0%; average were 75%、80%、72.73%、11.11%、0%, respectively. According to multiple linear regression analysis the dosage of tigecycline is closely related with AUC (P<0.01), and the age, sex, APACHEII scores, serum albumin and serum creatinine was no significant. In this study,17 patients with clinically effective, the effective rate was 43.59%. The effective rate of low dose group lungs, abdominal clinical efficiency were 27.27% and 50%, respectively while that of high dose group lungs, abdominal, skin and soft tissue clinical efficiency were 57.14%,66.67%,37.5%.21 patients clear bacterial, the total bacterial clearance rate was 53.85%, the low-dose group lungs, abdominal bacterial clearance rates were 36.36% and 70% respectively; high dose group lungs, abdominal, skin and skin and soft tissue bacterial clearance rates were 71.42%,66.67%,37.5%. Tigecycline against Acinetobacter baumannii, Klebsiella pneumoniae and Escherichia coli clearance rates were 44.83%,46.67% and 80%. Respiratory, abdominal, skin and soft tissue pathogen eradication rates were 48%,56.25%,37.5%. The 28d mortality of the AUIC not up to standard group is higher than the AUIC up to standard group, the difference was statistically significant; the bacterial clearance rate of the AUIC up to standard group is higher than the AUIC not up to standard group, the difference was statistically significant. APACHEⅡ<20 clinical effectiveness in patients with bacterial clearance rate of APACHEⅡ>20 (56.52% vs 25%.60.87% vs 43.75%), there are significant differences between the two groups (P<0.01).7 patients with adverse reactions, adverse reaction rate was 23.08%, mainly gastrointestinal symptoms such as nausea, vomiting in 4 cases,3 cases of liver dysfunction, coagulation abnormalities in 2 cases;2. When the PK/PD target was 100%T>MIC with different MIC value 0.5,1,2,4,8μXg/ml, in the mild group compliance rate were 100%.100%.100%.100%、81.8%, severe group compliance rates were 100%.100%、100%.100%.66.7%; to 100%T>4 x MIC in the mild group compliance rate were 100%.100%.81.8%.18.2%.0%, severe group compliance rate was 100%.100%. 66.7%.22.2%.0% respectively. APACHEⅡ score, clinical outcomes and meropenem serum trough concentrations were significantly correlated(P<0.05). For mild and severe group, and the positive clinical outcome of m ild and severe group were 40% and 25%, and 1 patients with nausea and vomiting.Conclusion:1. The dosage should be adjusted considering the special physiological and pathological state of the severe sepsis patients, which lead to changes in PK/PD properties of tigecycline. The tigecycline clinical compliance rate (especially MIC>2.0 μg/ml) is low, and therefore clinical monitoring is necessary. Tigecycline AUIC can reflect the clinical efficacy of tigecycline against multi-drug resistant good sensitivity for patients with abdominal infection normal dose which has better clinical efficacy and bacterial eradication; for the lungs infection in patients with high doses of tigecycline (100 mg ql2h) is more conducive to clinical efficacy and bacterial eradication; skin and soft tissue infections and less efficient clinical bacterial clearance. The 28d mortality of the tigecycline AUIC not up to standard group is higher than the AUIC up to standard group(44.44% vs 14.29%; the bacterial clearance rate of the AUIC up to standard group is higher than the AUIC not up to standard group(90.48% vs 11.11%);APACHEII score with clinical efficacy and bacterial clearance rate are inversely proportional relationship. Dose of tigecycline is greater impact AUC, the site of infection and bacteria for the MIC values of tigecycline is greater impact AUIC, so we should consider these factors for the regimen.2% The rate of meropenem serum trough concentrations reaching the standard is low in severe sepsis patients when MIC>2.0 μg/ml, so constant monitoring is required. APACHEⅡ score, clinical outcomes and meropenem serum trough concentrations were significantly correlated. |
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