Effect of vancomycin loading dose on clinical outcome in critically ill patients with methicillin-resistant Staphylococcus aureus pneumonia

BackgroundVancomycin is the treatment of choice for serious methicillin-resistant Staphylococcus aureus (MRSA) infections. Current guidelines recommend giving an initial loading dose (LD) of 25–30 mg/kg to rapidly increase the serum concentration. However, high-quality evidence for the clinical benefit of LD is lacking. Herein, we aim to examine the association between vancomycin LD and clinical outcome.MethodsA retrospective cohort study was conducted on adult patients treated for MRSA pneumonia with vancomycin in medical intensive care units from April 2016 to August 2018. MRSA pneumonia was defined by the Centers for Disease Control and National Healthcare Safety Network definition. The primary outcome was the clinical cure of pneumonia. Secondary outcome measures included time to pharmacokinetic (PK) target attainment, microbiological cure, acute kidney injury, and all-cause mortality.ResultsA total of 81 patients were included; of these 22 (27.2%) received LD. The mean initial dose was significantly higher in the LD group. Clinical cure was similar in both groups (68.2% vs. 66.1% in the LD and non-LD groups, respectively; P=0.860). No significant difference was observed in the microbiological cure, all-cause mortality, and incidence of acute kidney injury. Furthermore, no difference was observed in terms of time to PK target attainment (69.2 vs. 63.4 h in the LD and non-LD groups, respectively; P=0.624). Vancomycin minimum inhibitory concentration of <2 mg/L was identified as an independent predictive factor for clinical cure in multivariable analysis, whereas vancomycin LD was not.ConclusionsInitial LD is not associated with better clinical outcome or rapid pharmacological target attainment in critically ill patients with MRSA pneumonia. Further studies are warranted to provide better evidence for this widely recommended practice.     

低分子肝素钙联合双抗治疗进展性缺血性脑卒中疗效观察

目的：观察低分子肝素钙联合双抗治疗进展性缺血性脑卒中的临床效果。方法将100例进展性缺血性脑卒中患者随机分为观察组和对照组各50例。观察组采用氯吡格雷及拜阿司匹林与低分子肝素钙联合治疗,对照组采用血塞通常规治疗。观察2组患者治疗前后纤维蛋白原（Fg）水平、凝血酶原时间（PT）及神经功能缺损评分变化。结果观察组治疗总有效率为94％高于对照组的70％,差异有统计学意义（P ﹤0.05）;2组疗前 Fg、PT 比较差异无统计学意义（P ﹥0.05）,疗后2周,观察组 Fg 水平低于对照组,PT 大于对照组,差异均有统计学意义（P ﹤0.05）;治疗前2组患者神经功能缺损评分比较差异无统计学意义（P ﹥0.05）,治疗后观察组神经功能缺损评分低于对照组（P ﹤0.05）。结论采用低分子肝素钙联合双抗血小板治疗进展性缺血性脑卒中,可改善神经神经功能缺损情况,提高临床治疗效果,改善脑微循环,对改善患者预后有非常重要的价值。     

1例冠心病伴2型糖尿病患者服用阿托伐他汀钙引发的思考

通过考察1例冠心病伴2型糖尿病患者服用他汀类药物治疗效果,研究阿托伐他汀在糖尿病患者中使用的合理性。患者入院时饭后血糖高达14.76 mmol/L,血糖监控表显示患者在22日中餐前,23日早餐、中餐前血糖均跃7 mmol/L,患者空腹血糖控制不佳,23日临床药师与医生查房建议患者加大甘精胰岛素用量,晚上皮下注射甘精胰岛素加至20 U,24日晚餐前后血糖仍跃7 mmol/L,血糖控制不佳。由此可知,本例患者应用他汀药物可能会导致患者血糖异常,但相对心血管不良风险,本例使用阿托伐他汀是合理的。     

皮下注射低分子肝素钙预防烧伤植皮后深静脉血栓形成的效果评价

目的：评估皮下注射低分子肝素钙对预防烧伤植皮后深静脉血栓(DVT)形成的效果。方法选取2013年1月~2014年12月本院收治的79例烧伤后需植皮的患者,其中皮下注射低分子肝素钙预DVT患者41例设为治疗组。植皮术后仅使用红外线治疗仪照射,硫酸镁热敷,活动肌肉组织等基础措施的38例为对照组。统计血浆D-二聚体(D-dimer)浓度、血小板计数、植皮成活率、创面愈合时间、感染病例数、组织器官出血病例数和DVT形成数等指标。结果治疗组术后第3、7、11、15 d的血浆D-dimer浓度均低于对照组(P<0.05);对照组的血栓形成率为10.5%,明显高于治疗组的0(P<0.05);两组术前1 d的D-dimer浓度、血小板计数,植皮成活率、创面愈合时间、感染及出血发生率差异无统计学意义(P>0.05)。结论皮下注射低分子肝素钙对预防烧伤植皮术后患者DVT形成有一定的临床意义。     

Increased Proinflammatory Cytokine Production and Decreased Cholesterol Efflux Due to Downregulation of ABCG1 in Macrophages Exposed to Indoxyl Sulfate

One of the possible causes of enhanced atherosclerosis in patients with chronic kidney disease (CKD) is the accumulation of uremic toxins. Since macrophage foam cell formation is a hallmark of atherosclerosis, we examined the direct effect of indoxyl sulfate (IS), a representative uremic toxin, on macrophage function. Macrophages differentiated from THP-1 cells were exposed to IS in vitro. IS decreased the cell viability of THP-1 derived macrophages but promoted the production of inflammatory cytokines (IL-1β, IS 1.0 mM: 101.8 ± 21.8 pg/mL vs. 0 mM: 7.0 ± 0.3 pg/mL, TNF-α, IS 1.0 mM: 96.6 ± 11.0 pg/mL vs. 0 mM: 15.1 ± 3.1 pg/mL) and reactive oxygen species. IS reduced macrophage cholesterol efflux (IS 0.5 mM: 30.3% ± 7.3% vs. 0 mM: 43.5% ± 1.6%) and decreased ATP-binding cassette transporter G1 expression. However, lipid uptake into cells was not enhanced. A liver X receptor (LXR) agonist, T0901317, improved IS-induced production of inflammatory cytokines as well as reduced cholesterol efflux. In conclusion, IS induced inflammatory reactions and reduced cholesterol efflux in macrophages. Both effects of IS were improved with activation of LXR. Direct interactions of uremic toxins with macrophages may be a major cause of atherosclerosis acceleration in patients with CKD.     

Induction of Suicidal Erythrocyte Death by Cantharidin

The natural phosphoprotein phosphatase inhibitor cantharidin, primarily used for topical treatment of warts, has later been shown to trigger tumor cell apoptosis and is thus considered for the treatment of malignancy. Similar to apoptosis of tumor cells, erythrocytes may undergo eryptosis, a suicidal cell death characterized by cell shrinkage and translocation of cell membrane phosphatidylserine to the erythrocyte surface. Signaling of eryptosis includes increase of cytosolic Ca²⁺-activity ([Ca²⁺]_i), ceramide, oxidative stress and dysregulation of several kinases. Phosphatidylserine abundance at the erythrocyte surface was quantified utilizing annexin-V-binding, cell volume from forward scatter, [Ca²⁺]_i from Fluo3-fluorescence, ceramide from antibody binding, and reactive oxidant species (ROS) from 2′,7′-dichlorodihydrofluorescein diacetate (DCFDA) fluorescence. A 48 h treatment of human erythrocytes with cantharidin significantly increased the percentage of annexin-V-binding cells (≥10 μg/mL), significantly decreased forward scatter (≥25 μg/mL), significantly increased [Ca²⁺]_i (≥25 μg/mL), but did not significantly modify ceramide abundance or ROS. The up-regulation of annexin-V-binding following cantharidin treatment was not significantly blunted by removal of extracellular Ca²⁺ but was abolished by kinase inhibitor staurosporine (1 μM) and slightly decreased by p38 inhibitor skepinone (2 μM). Exposure of erythrocytes to cantharidin triggers suicidal erythrocyte death with erythrocyte shrinkage and erythrocyte membrane scrambling, an effect sensitive to kinase inhibitors staurosporine and skepinone.