4种非发酵糖革兰阴性杆菌氨基糖苷类修饰酶基因研究

目的 分析解放军第98医院临床分离的4种非发酵糖革兰阴性杆菌中氨基糖苷类修饰酶(AMEs)基因存在状况.方法 在2000年7月至2004年10月间从临床分离60株鲍曼不动杆菌(Ab)、30株铜绿假单胞菌(Pa)、19株嗜麦芽窄食单胞菌(Sm)和15株黄杆菌属细菌(Fb),采用PCR及序列分析法分析9种AMEs基因aac(3)-Ⅰ、aac(3)-Ⅱ、aac(3)-Ⅲ、aac(3)-Ⅳ、aac(6')-Ⅰ、aac(6')-Ⅱ、ant(3')-Ⅰ、ant(2')-Ⅰ和aph(3')-Ⅵ.结果 Ab、Pa、Sm和Fb中9种AMEs基因总阳性率分别为81.7%、86.7%、10.5% 和0.0%.Ab、Pa和Sm中分别检出8种、5种和2种基因.aac(3)-Ⅲ基因均阴性,各菌种中阳性率最高的基因分别是Pa中aac(3)-Ⅱ(76.7%)、Ab中ant(3')-Ⅰ (60.0%)、Sm 中aac(6')-Ⅱ和ant(2')-Ⅰ(均为10.5%).结论 临床分离的非发酵糖革兰阴性杆菌(除Fb外)中至少存在8种AMEs基因,Pa及Ab中AMEs基因携带率高.     

Determinants of inappropriate empirical antibiotic treatment: systematic review and meta-analysis

This systematic review assessed study-level determinants of non-covering (inappropriate) empirical antibiotic treatment (IEAT), focusing on the influence of study years and the prevalence of multidrug-resistant organisms (MDROs) in the study. Prospective and retrospective observational studies reporting on the association between IEAT and mortality in adult patients with microbiologically documented infections published between 2008–2016 were included. A meta-analysis of IEAT rates was conducted using a random-effects model. Subgroup analyses and mixed-effect single-covariate meta-regression were conducted to identify the association between clinical and methodological study-level covariates and IEAT rates. Heterogeneity was assessed using the I² measure of inconsistency. Multi-covariate meta-regression was conducted including variables with a P-value of <0.1 on single-covariate analysis. A total of 191 studies were included assessing 73 595 patients, most commonly with bacteraemia. The pooled IEAT event rate was 32% [95% confidence interval (CI) 30–35%], with large heterogeneity (I²?=?97.7%). On multi-covariate analyses, the prevalence of any MDRO [odds ratio (OR) per 10% increase in prevalence?=?1.11, 95% CI 1.07–1.15], Acinetobacter spp. specifically (OR?=?1.99, 95% CI 1.22–3.25) and advancing study years were associated with IEAT rates (OR?=?1.03, 95% CI 1.00–1.06 per year). MDRO rates were independently associated with mortality rates in the studies, adjusting to the rate of IEAT. The prevalence of MDROs, mainly multidrug-resistant Gram-negative bacteria, is significantly associated with the probability of prescribing IEAT and mortality rates in recent studies. We show how antibiotic resistance impacts patient management and outcomes.     

Effect of red wine polyphenol dietary supplementation on two phase II enzymes in liver of hyperhomocysteinemic mice

Hyperhomocysteinemia leads to diverse clinical manifestations, notably liver disease. The pathogenicity of homocysteine is believed to be due to its ability to produce oxidative stress. Paraoxonase-1 (Pon1), a phase I xenobiotic-metabolizing enzyme (XME) synthesized by liver with anti-oxidative properties within the circulating system is down regulated in case of hyperhomocysteinemia. In a previous study, we have shown that red wine polyphenol extract (PE) supplementation induces a decrease in plasma homocysteine level and an increase in hepatic Pon1 gene expression concomitant with an increase in hepatic and plasma Pon1 activity in a murine model of hyperhomocysteinemia. In the present study, we analyzed the effect of PE supplementation on two phase II XME: NAD(P)H:quinone oxidoreductase (Nqo1) and arylamine-N-acetyltransferase (Nat) family. We found that hyperhomocysteinemia leads to a decrease of hepatic Nqo1 gene expression and activity with a reversal effect of PE supplementation. We also found that hyperhomocysteinemia-induced decrease of peroxynitrite level is associated with an increase of hepatic total Nat activity mainly due to the Nat2 isoform with a reversal effect of PE supplementation. Our results show a beneficial effect of PE supplementation on two phase II enzymes which are altered in case of hyperhomocysteinemia.