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.     

Activity of tedizolid against gram-positive clinical isolates causing infections in Europe and surrounding areas (2014–2015)

Activities of tedizolid and comparators were evaluated against gram-positive isolates responsible for skin and skin structure infections, pneumonia, and bloodstream infections. Non-duplicate gram-positive isolates (8011) were collected from 20 European countries/regions.

Tedizolid (0.12?mg/L) showed similar results of minimum inhibitory concentration required to inhibit the growth of 50% of organisms (MIC₅₀) regardless of pathogen/group or infection type, except for coagulase-negative staphylococci, Enterococcus faecalis, and viridans group streptococci (VGS), against which tedizolid had MIC₅₀ values of 0.06, 0.25, and 0.06?mg/L, respectively. Similar results of tedizolid MIC₅₀ and minimum inhibitory concentration required to inhibit the growth of 90% of organisms (MIC₉₀) (MIC_50/90, 0.12/0.12?mg/L) were obtained against methicillin-resistant Staphylococcus aureus and methicillin-susceptible S. aureus. Tedizolid, linezolid, and daptomycin were active against enterococci. Tedizolid (MIC₉₀, 0.12–0.25?mg/L), ceftaroline (MIC₉₀, 0.12?mg/L), and vancomycin (MIC₉₀, 0.25–0.5?mg/L) had the lowest MIC₉₀ values against Streptococcus pneumoniae and VGS, whereas ceftaroline (MIC₉₀, ≤0.015?mg/L), penicillin (MIC₉₀, ≤0.06?mg/L), ceftriaxone (MIC₉₀, ≤0.06–0.12?mg/L), and tedizolid (MIC₉₀, 0.12?mg/L) were the most potent against β-haemolytic streptococci.

Tedizolid displayed potent activity against gram-positive isolates from Europe, regardless of infection type.     

The first case of teeth discoloration induced by linezolid in children in China Mainland

Linezolid is an oxazolidinone antimicrobial agent often used to treat multidrug-resistant Gram-positive bacterial infections. The common adverse reactions of linezolid are diarrhea, nausea, headache and bone marrow suppression, and so on. Here, we report the first case of teeth discoloration induced by linezolid linked with extrinsic discoloration in China Mainland. This case report highlights a rare adverse reactions of a commonly used antibiotic.     

Dose optimization of moxifloxacin and linezolid against tuberculosis using mathematical modeling and simulation

Introduction

There is an urgent need for new anti-tuberculosis (TB) drugs and optimization of current TB treatment. Moxifloxacin and linezolid are valuable options for the treatment of drug-resistant TB; however, it is crucial to find a dose at which these drugs not only show high efficacy but also suppress the development of further drug resistance.

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。     

利奈唑胺对比万古霉素治疗重症感染的疗效评价

目的评价利奈唑胺与万古霉素在治疗重症感染方面的疗效。方法筛选2020年2—5月入住ICU的确诊或高度怀疑革兰阳性球菌感染患者共19例,随机分为利奈唑胺组及万古霉素组,分别给予常规剂量治疗,比较两组炎症指标、临床疗效及不良反应。结果治疗后,利奈唑胺组相对于万古霉素组在白细胞、降钙素原、C反应蛋白、白介素-6变化的差异无统计学意义,利奈唑胺组临床显效率为55.56%,万古霉素组为60.00%,组间比较差异无统计学意义,两组不良反应发生率比较,差异无统计学意义。结论利奈唑胺对革兰阳性球菌重症感染的疗效与万古霉素无明显差异,临床疗效肯定。     

利奈唑胺葡萄糖注射液药物利用评价标准的建立及在重症医学科的应用

目的 建立利奈唑胺葡萄糖注射液的药物利用评价（DUE）标准,评价利奈唑胺葡萄糖注射液在重症医学科（ICU）的应用情况,为临床合理用药提供参考。方法 参考药品说明书、抗菌药物临床应用指导原则、相关管理规范,建立利奈唑胺葡萄糖注射液的DUE标准,并对2020年7月至2021年12月合肥市第二人民医院ICU使用利奈唑胺葡萄糖注射液的病历进行回顾性分析。结果 共纳入应用利奈唑胺葡萄糖注射液的病人82例,临床有效率52.44%(43/82)、药品不良反应（ADR）发生率4.88%(4/82),经评估该院ICU的利奈唑胺葡萄糖注射液应用在剂量、处方权限、病程记录、不良反应监测方面均符合评价标准要求,但仍有一些指标存在问题,如经验性用药较多89.02%(73/82)、用药前病原学检查率较低48.78%(40/82)、药物疗程不足45.12%(37/82),主要由病人出院或发生ADR造成。结论 建立的利奈唑胺葡萄糖注射液的DUE标准实用性较强,可及时发现利奈唑胺葡萄糖注射液在使用过程中的问题。     

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。     

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.