Detection of vancomycin variable enterococci (VVE) among clinical isolates of Enterococcus faecium collected across India-first report from the subcontinent

PurposeEmergence of vancomycin variable enterococci (VVE) poses a challenge to empiric vancomycin therapy. Vancomycin-variable enterococci (VVE) are vanA-positive, yet phenotypically vancomycin-susceptible enterococci that can switch to a vancomycin-resistant phenotype when exposed to vancomycin. The aim of the present study was to determine the prevalence of VVE in India.MethodsIsolates of phenotypically vancomycin susceptible Enterococcus faecium from 20 tertiary care hospitals across India were collected and tested for the presence of vanA, vanR, vanS, vanB and vanC genes by conventional PCR using previously published primers. Isolates positive for vanA gene were considered as VVE.ResultsThe prevalence of VVE was 1.5% (5/340). Only one VVE isolate was positive for vanR and vanS, and all the isolates were negative for vanB and vanC.ConclusionsAlthough the prevalence is low, our finding emphasizes the importance of routinely screening for van genes in enterococci that are phenotypically susceptible. Silenced vanA able to escape detection and revert to resistance during vancomycin therapy represents a new challenge in clinical settings.     

反复粪便培养金黄色葡萄球菌阳性老年患者口服万古霉素效果评价

目的 通过探讨肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者口服万古霉素的效果，为此类患者提供一种潜在的治疗方案。方法 前瞻性分析吉林大学第一医院干部病房2015 年9 月～2018 年12 月收治的186 例肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者。根据是否口服万古霉素治疗分为万古组和对照组。收集两组患者的一般临床资料，比较两组患者试验前后万古霉素血药浓度、血常规、降钙素原（PCT）、C 反应蛋白（CRP），试验期间粪便培养结果、体温、抗生素使用情况。结果 试验治疗期间，万古组便培养转阴率高于对照组，差异有统计学意义（P＜0.05）；万古组发热率（29.75%）低于对照组的34.77%，差异有高度统计学意义（P＜0.01）；万古组抗生素使用率（4.49%）低于对照组的19.23%，差异有高度统计学意义（P＜0.01）。试验前两组白细胞、中性粒细胞计数、中性粒细胞比例、PCT、CRP 比较，差异无统计学意义（P＞0.05）；试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于对照组，差异有高度统计学意义（P＜0.01）。试验后万古组白细胞、中性粒细胞计数、中性粒细胞比例、CRP 低于试验前，差异有高度统计学意义（P＜0.01）。结论 口服万古霉素可能提高肠道非急性感染期反复粪便培养金黄色葡萄球菌阳性的老年患者粪便转阴率，减少发热及抗生素的应用，降低炎症细胞水平，可能是此类患者一种潜在的临床治疗方案。     

万古霉素脑室内注射治疗成人中枢神经系统感染的研究进展

中枢神经系统(CNS)周围的屏障以及多重耐药菌的出现对有效治疗CNS感染提出了治疗挑战。万古霉素是一种糖肽类抗生素，用于治疗和预防由革兰阳性菌引起的各种细菌感染，包括耐甲氧西林金黄色葡萄球菌(MRSA)。它也用于肠球菌、链球菌和甲氧西林敏感的金黄色葡萄球菌(MSSA)等引起的感染。万古霉素被推荐作为颅内感染的一线治疗药物。然而，通过静脉(IV)输注给药时，万古霉素在脑脊液(CSF)中的渗透是有限的。万古霉素通过脑室内(IVT)给药可绕过血脑屏障直接到达目标部位，实现高浓度以获得更好的杀菌作用。万古霉素IVT给药的适应症主要包括对IV抗生素反应较差的脑膜炎、脑室炎、颅内装置感染和脑脓肿。本文综述了成人万古霉素IVT给药的研究现状，旨在为临床实践提供参考。根据现有证据，使用万古霉素IVT给药治疗CNS感染是安全有效的。万古霉素IVT给药的最佳给药方案需要考虑到不同患者CNS的病理生理学特点并根据具体情况进行临床判断。     

Concomitant vancomycin and piperacillin/tazobactam treatment is associated with an increased risk of acute kidney injury in Japanese patients

IntroductionRecent studies have corroborated that the co-administration of vancomycin (VCM) and piperacillin/tazobactam (PT) is correlated with an increased incidence of acute kidney injury (AKI). However, evidence directed at the Japanese population is scarce. Therefore, we conducted a retrospective study to compare the occurrence of AKI among Japanese patients who received VCM with PT (VP therapy) and VCM with another β-lactams (VA therapy).MethodsThe present study, performed at Tsuyama Chuo Hospital between June 2012 and December 2018, included adult patients who received VCM and β-lactam antibiotics for ≥48 h. We defined the primary outcome as the incidence of AKI based on the risk, injury, failure, loss, and end-stage kidney disease criteria. Patients' clinical characteristics and outcomes were reviewed and compared between the two groups with univariate and multivariate logistic regression analyses. Subgroup analysis was conducted by stratifying the patients’ baseline hospital admittance status, as intensive care unit or general wards.ResultsWe analyzed 272 patients (92 V P therapy and 180 VA therapy). Univariate analysis revealed a significant difference in AKI development between VP and VA therapy (25.0% vs 12.2%; p < 0.01). A multivariate analysis demonstrated that VP therapy and VCM initial trough levels ≥15 μg/mL were associated with an incidence of AKI. Patients at general wards, rather than those admitted at an intensive care unit, developed AKI with VP therapy (p = 0.02).ConclusionVP therapy was associated with an increased risk of AKI compared to that with VA therapy among the Japanese population.     

1例重度急性胰腺炎患者抗感染治疗的药学监护

摘 要临床药师参与1例重度急性胰腺炎患者的药物治疗,结合患者病史、临床症状及实验室指标等,根据病原学检测结果,借助万古霉素血药浓度监测进行抗感染方案调整,并协助医生对患者制定个体化用药方案。经治疗后,患者病情得到基本控制,且未出现相关药品不良反应。提示临床药师在参与患者治疗过程中,可结合患者特殊的生理病理状态、药物浓度监测及临床反应等,协助临床医师优化药物治疗方案,提高患者用药的有效性和安全性。     

Schwartz公式计算所得的儿童肾小球滤过率和万古霉素理想剂量之间的相关性研究

摘 要 目的：了解Schwartz公式计算所得到的儿童肾小球滤过率（GFR）和万古霉素理想剂量之间的关联性。评估是否可以通过GFR估算出万古霉素的理想剂量。方法: 通过治疗药物监测,计算出患儿万古霉素的清除率和理想日剂量。依据患儿血肌酐值,以Schwartz公式计算所得GFR值,观察不同GFR值范围内相对应的万古霉素日剂量分布,并采用线性回归分析法,评价GFR和上述药动学参数的相关性。结果: GFR值超过200 ml·min-1·(1.73m2)-1时,72.22%的患者理想剂量＞60 mg·kg-1·d-1;线性回归分析结果, GFR对于清除率和理想日剂量之间存在统计学意义上的线性关系,但其回归系数R2分别仅为0.307和0.361,GFR和理想日剂量之间的回归方程为Y=0.169X+29.577。结论: 由Schwartz公式所得的GFR值和万古霉素理想日剂量之间存在着统计学意义上的的线性关系,但是其相关性强度不高,无法用来准确估算万古霉素剂量。     

万古霉素N4氨基的还原烷基化条件优化

目的 优化万古霉素N4氨基还原烷基化的反应条件。方法 以万古霉素为原料,筛选还原烷基化反应的溶剂、还原剂、醛用量和反应温度,用HPLC方法测定原料和产物含量。结果 确立了以甲醇/二甲基亚砜=1:1为溶剂、硼烷叔丁胺为还原剂、1.3倍醛用量、缩合温度65℃、还原温度为室温的最优反应条件。结论 利用本文优化后的条件可以有效合成万古霉素N4氨基还原烷基化产物,研究结果为其他糖肽类抗生素的半合成衍生化提供技术基础。     

Fidaxomicin versus oral vancomycin for severe Clostridium difficile infection: a retrospective cohort study

ObjectivesThis study was conducted to compare clinical outcomes of fidaxomicin versus oral vancomycin in the management of severe Clostridium difficile infection (CDI).MethodsThe investigation was a retrospective, multicentre, propensity score-matched analysis using a national clinical administrative database. Veterans treated for severe CDI from any Veterans Affairs Medical Center between 1 June 2011 and 30 June 2017 were included if they received fidaxomicin or an oral vancomycin regimen for treatment. The two groups were matched by the nearest-neighbour method from a propensity score derived from independent variables associated with the selection of a fidaxomicin course.ResultsPropensity score matching resulted in two well-matched cohorts consisting of 213 fidaxomicin and 639 oral vancomycin courses. No statistically-significant difference was found for the primary outcome of combined clinical failure or recurrence (68/213 (31.9%) versus 163/639 (25.5%), respectively, p 0.071). Additionally, no statistically significant differences were found for the secondary outcomes of 30-day (23/213 (10.8%) versus 75/639 (11.7%), respectively, p 0.71), 90-day (48/213 (22.5%) versus 140/639 (21.9%), respectively, p 0.85), and 180-day mortality (62/213 (29.1%) versus 186/639 (29.1%), respectively, p 1.0) between the two treatment groups.ConclusionsCourses of fidaxomicin or oral vancomycin for severe CDI resulted in similar treatment outcomes. Study findings are consistent with current treatment guideline recommendations for the use of either agent in the management of severe CDI.     

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。     

Occurrence of a USA300 vancomycin-intermediate Staphylococcus aureus

A vancomycin-intermediate Staphylococcus aureus (VISA) isolated from the blood of a 46-year-old patient with endocarditis was determined to be pulsed-field type USA300, daptomycin nonsusceptible, and positive for the Panton-Valentine leukocidin genes. Development of the VISA phenotype does not appear limited to traditional health care strains of S. aureus.