In-vitro activity of ceftriaxone combined with newer agents against MRSA

In this study, in vitro synergism in combinations of agents as ceftriaxone/dalbavancin, ceftriaxone/linezolid and ceftriaxone/daptomycin against MRSA strains were investigated. Thirty clinical MRSA strains were tested. The minimum inhibitory concentrations of all antibiotics were determined using reference broth microdilution method. In-vitro activities of antibiotics combined against the strains were tested using two-dimensional checkerboard microdilution method. Results were interpreted as follows: synergy = FICI ≤0.5; ‘no interaction’ effect = FICI ?0.5-≤4; antagonism = FICI ?4. The MIC₅₀, MIC₉₀ and MIC_range of ceftriaxone, daptomycin, dalbavancin and linezolid were found as 128, 1024 and 16-2048 mg/L; 1, 1 and 0.5–1 mg/L; 0.12, 0.12 and 0.03–0.12 mg/L; and 1, 2 and 1–2 mg/L, respectively. Our results showed that the frequency of synergistic effects (FICI: ≤0.5) of three combinations were all at the same rate of 77% (23/30). No in vitro antagonism (FICI >4) was observed.     

Successful treatment of linezolid-induced severe lactic acidosis with continuous venovenous hemodiafiltration: A case report

Linezolid is an oxazolidinone antibiotic. Linezolid-associated lactic acidosis has been reported in 6.8% of linezolid-treated patients. Lactic acidosis is associated with poor clinical outcomes, with high blood lactate levels resulting in organ dysfunction and mortality. This case report describes the development of lactic acidosis in a 64-year-old Chinese woman who had received 33 days of treatment with antituberculosis drugs and 28 days of treatment with oral linezolid for tuberculous meningitis. Severe lactic acidosis was reversed by withdrawing antituberculosis drugs and using continuous venovenous hemodiafiltration (CVVH). When the patient's condition was stable, she was transferred to the infectious disease department, and antituberculosis drugs, with the exception of linezolid, were reintroduced. This did not result in recurrence of lactic acidosis. The causal relationship between lactic acidosis and linezolid was categorized as ‘probable’ on the Adverse Drug Reaction Probability Scale. This case demonstrates that CVVH has potential as an alternative to discontinuation of linezolid alone for rapid reversal of linezolid-associated severe lactic acidosis.     

Clinical impact of vancomycin heteroresistance in staphylococcal strains involved in neonatal sepsis: Discussion of a case report

Heteroresistance to vancomycin (HRV) represents a decreased susceptibility to vancomycin and is frequently observed in multidrug-resistant coagulase-negative staphylococci. The clinical significance of such heteroresistance is controversial, but several failures of vancomycin therapy have been related to HRV, especially in the neonatal population. Here we report the case of a preterm neonate, born at 26 weeks of gestation, who developed sepsis due to a multidrug-resistant HRV Staphylococcus capitis isolate. Bacteremia persisted despite adequate vancomycin serum concentration and catheter removal. The patient finally recovered after replacing vancomycin by linezolid. Through this case report, we would like to alert clinicians of the potential clinical impact of HRV and to discuss the lack of therapeutic alternatives in neonates.     

利奈唑胺的合成

对利奈唑胺合成工艺进行优化。以吗啉和3,4-二氟硝基苯为原料,经取代、还原反应得到中间体5;（R）-环氧氯丙烷7、邻苯二甲酰亚胺钾盐6发生取代反应合成中间体9;最后中间体5和9经取代、环化、水解合成目标产物利奈唑胺,总收率36.5%（以3,4-二氟硝基苯计）。     

利奈唑胺对耐甲氧西林金黄色葡萄球菌细菌生物膜的抑制与消除活性及体内外抗菌活性研究

目的：系统性评价利奈唑胺对2013~2014年耐甲氧西林金黄色葡萄球菌（MRSA）临床分离株细菌生物膜（BBF）的活性及体内外抗菌效果。方法：体外试验测定最低抑菌浓度（MIC）;最低杀菌浓度（MBC）;最小抑制BBF浓度（MBIC）和最低BBF消除浓度（MBEC）;活菌计数法绘制时间-杀菌曲线（KCs）;体内试验采用小鼠MRSA全身感染模型,尾静脉给药保护小鼠后测定半数有效剂量（ED50）;建立免疫低下小鼠MRSA大腿感染模型,记录尾静脉给药24 h后大腿组织菌量的变化。结果：利奈唑胺对2013~2014年临床分离的60株MRSA均敏感;对金黄色葡萄球菌BBF的MBIC值与万古霉素相当,敏感性显著高于阿莫西林;体内试验中,利奈唑胺对全身感染小鼠有很好的治疗效果,ED50小于万古霉素与阿莫西林;对免疫低下MRSA大腿感染模型小鼠的保护作用也要优于万古霉素和阿莫西林。结论：利奈唑胺对2013~2014年分离的MRSA临床菌株体内外活性均较高,尤其对MRSA的细菌生物膜也显示了极强的抑制作用。     

利福霉素钠注射液联合利奈唑胺注射液对重症革兰阳性球菌感染患者炎症反应、血清降钙素原水平及不良反应的影响

目的:探讨利福霉素钠注射液联合利奈唑胺注射液对重症革兰阳性球菌感染患者炎症反应、血清降钙素原(PCT)水平及不良反应的影响。方法:选取2018年5月至2019年9月商丘市第一人民医院收治的重症革兰阳性球菌感染患者60例作为研究对象,按照随机数字表法分为研究组和对照组,每组30例。对照组患者给予利奈唑胺注射液治疗,研究组患者在对照组的基础上给予利福霉素钠注射液治疗。比较两组患者的临床疗效、炎症指标[白细胞计数(WBC)、超敏C反应蛋白(hs-CRP)、白细胞介素1β(IL-1β)及白细胞介素10(IL-10)]水平、血清PCT水平及不良反应发生情况的差异。结果:研究组患者的总有效率明显高于对照组[90.00%(27/30)vs.66.67%(20/30)],差异有统计学意义(P<0.05)。治疗后,两组患者血清WBC、CRP及IL-1β水平均较治疗前明显降低,血清IL-10水平较治疗前明显升高;且研究组患者血清WBC、CRP及IL-1β水平明显低于对照组,血清IL-10水平明显高于对照组,上述差异均有统计学意义(P<0.05)。治疗后,两组患者血清PCT水平均较治疗前明显降低,且研究组患者明显低于对照组,差异均有统计学意义(P<0.05)。研究组、对照组患者的不良反应发生率分别为23.33%(7/30)、26.67%(8/30),差异无统计学意义(P>0.05)。结论:利福霉素钠注射液联合利奈唑胺注射液治疗重症革兰阳性球菌感染的临床效果显著,能够有效降低患者血清PCT水平,改善炎症反应,缓解感染症状,具有一定的临床应用价值。     

Evaluation of the relationship between linezolid exposure and hyponatremia

IntroductionAims of this study were (a) to assess the development ratio of hyponatremia during treatment with linezolid and (b) to evaluate the relationship between the risk of hyponatremia and linezolid exposure and patient background.MethodClinical data including linezolid serum concentrations and serum sodium values were collected at Toyama University Hospital and Kyorin University Hospital. Data from 89 patients were used for the analysis, and a nadir serum sodium level ≤130 mmol/L during the treatment with linezolid was defined as hyponatremia. Mann-Whitney's U test was used to evaluate the effects of the area under the time-concentration curve (AUC) of linezolid at the nadir sodium level, clinical characteristics (e.g. laboratory data), and baseline serum sodium levels on the development of hyponatremia.ResultsThe hyponatremia was occurred in 21 of 89 patients (23.6%). Data are compared for baseline and nadir serum sodium levels of patients with and without hyponatremia. In both groups, nadir serum sodium levels were significantly different from those of the baseline values (P < 0.05). The values of AUC_0-12, accumulated AUC, baseline serum sodium levels and age were significantly different between patients with and without hyponatremia (P < 0.05).ConclusionsLinezolid exposure, age, and baseline sodium levels were detected as the risk factors for linezolid-related hyponatremia. Our findings suggest that regular monitoring of serum sodium levels is desirable during treatment with linezolid, especially for the elderly and patients with low serum sodium levels before the start of linezolid administration.     

利奈唑胺体外诱导金黄色葡萄球菌耐药的实验研究

目的：体外诱导金黄色葡萄球菌对利奈唑胺耐药,研究分析其耐药后菌株变化。方法用利奈唑胺浓度2倍递增的方法对9株临床分离金黄色葡萄球菌（5株MSSA、4株MRSA）和质控菌株ATCC25923进行体外诱导;PCR扩增诱导前后金黄色葡萄球菌23S rRNA的V区基因并测序、Blast比对,分析突变与耐药性的关系;比较诱导前后金黄色葡萄球菌的适应性以及对抗菌药物的耐药性变化。结果10株实验菌株中有9株诱导出稳定的利奈唑胺耐药性,其中5株耐药菌发生了突变;利奈唑胺耐药后金黄色葡萄球菌生长速率减慢,对其他抗菌药物耐药性也发生改变。结论经利奈唑胺诱导后金黄色葡萄球菌可以获得稳定耐药性,但同时也产生了适应性代价,其耐药机制与23S rRNA的V区基因突变相关,并且可能有其他耐药机制的参与。     

利奈唑胺与厄他培南治疗中度糖尿病足的疗效比较

目的：探讨利奈唑胺标准剂量和超治疗剂量对Q－T间期延长的影响。方法对60例利奈唑胺标准剂量治疗（600毫克,每12小时静点）住院患者进行12导联的心电图检查并观察Q－T间期的变化,并与50例利奈唑胺超治疗剂量（1200 mg,每12 h静点）及60例未应用利奈唑胺健康人员对比,以研究应用利奈唑胺治疗的患者Q－T间期的变化及其意义。结果利奈唑胺标准剂量治疗组及利奈唑胺超治疗剂量组的平均Q－T间期明显高于正常对照组,有统计学意义。利奈唑胺标准剂量治疗组及利奈唑胺超治疗剂量组的平均Q－T间期比较无显著差异,无统计学意义。结论利奈唑胺治疗组Q－T间期较对照组延长,使用利奈唑胺时注意监测心电图。     

利奈唑胺致血小板减少症发生状况及相关影响因素分析研究

目的：对使用利奈唑胺的住院患者进行回顾性调查分析,探讨利奈唑胺致相关性血小板减少症的发生情况及其影响因素。方法： 采用回顾性病例研究,对2015年6月至2017年12月某院260例使用利奈唑胺致相关性血小板减少症的发病情况进行分析,采用t检验（参数）和 Mann-Whitney U 检验（非参数）,χ2检验逐个分析各指标的组间差异性;采用条件Logistic回归分析不良反应/事件发生的影响因素及其标准回归系数（影响程度）。检验水准α=0.05。结果：纳入研究的260例患者中,有67例发生血小板减少症,发生比例为25.77%。单因素分析年龄分组中＞65岁人群中发病率较高,为35.40%（χ2=9.80,P=0.02）;≥3个联合用药组中发病率较高,为34.07%（χ2=11.02,P=0.01）。分析表明,实验室检查指标血小板基础值、用药天数、白蛋白、血清肌酐、尿素氮、尿酸与血小板减少症有关（P<0.05）。多因素Logistic回归分析提示：血小板基础值、用药天数、胆红素、肌酐与血小板减少症的发生密切相关。ROC诊断曲线预测分析曲线下面积为0.738,灵敏度68.71%,特异度71.50%,Youden指数0.40。结论：使用利奈唑胺后发生血小板减少症的发生率较高;单因素分析显示应重点关注高龄（≥65岁）、联合用药（≥3种）、基础血小板值低的患者;多因素分析显示,血小板基础值、用药天数、胆红素、肌酐与血小板减少症的发生密切相关。