Predicting adequacy of vancomycin regimens: A learning-based classification approach to improving clinical decision making

Clinicians' drug regimen decision making is critical, particularly when involving high-alert medications. In this study, we use decision-tree induction C4.5 and a backpropagation neural network to construct decision support systems for predicting the regimen adequacy of vancomycin, a glycopeptide antimicrobial antibiotic effective for Gram-positive bacterial infections. We comparatively evaluate the respective systems using a total of 987 clinical vancomycin cases collected from a major tertiary medical center in southern Taiwan. We supplement each system using Bagging and then examine the predictive power of the extended system. Overall, our evaluation results show the overall accuracy of the decision support system based on C4.5 or the neural network to be significantly higher than that of the benchmark one-compartment pharmacokinetic model. Use of Bagging can considerably improve the effectiveness of each system across different performance measures, particularly for cases of decision classes in which the base systems (i.e., without Bagging) perform modestly. Taken together, our evaluation results seem to favor the use of Bagging to enhance the performance of decision support systems constructed using decision-tree induction C4.5.     

OCT2、MDR1基因多态性与婴幼儿万古霉素血药浓度及临床疗效的相关性研究

目的: 考察有机阳离子转运体2（OCT2）和多药耐药基因1（MDR1）的基因多态性与婴幼儿万古霉素稳态谷浓度及临床疗效的相关性。方法: 收集91例万古霉素治疗的婴幼儿患者血样,酶免疫放大分析法测定万古霉素血药浓度,聚合酶链式反应（PCR）和DNA测序技术检测基因分型。比较OCT2 G808T（rs316019）和MDR1 C3435T（rs1045642）不同基因型对万古霉素谷浓度及临床疗效的影响。结果: 91例患者中,谷浓度达到10～20 μg/mL的比例为16.5%;5～<10 μg/mL和10～20 μg/mL浓度范围万古霉素的临床有效率（88%,93.3%）显著高于5 μg/mL以下浓度（44%）（P<0.05）,同时5～<10 μg/mL和10～20 μg/mL浓度范围万古霉素的临床有效率相近。OCT2 G808T纯合突变型（TT）患者万古霉素谷浓度（10.15±2.35） μg/mL和谷浓度/剂量比（0.98±0.27） μg·mL-1·mg-1·kg均显著高于野生型（GG）患者（6.92±2.83） μg/mL和（0.59±0.22） μg·mL-1·mg-1·kg（P<0.05）;同时,TT型患者临床有效率（100%）明显高于GG型（73.2%）（P<0.05）;而MDR1 C3435T突变型和野生型患者的万古霉素谷浓度、谷浓度/剂量比及临床疗效相近（P>0.05）。结论: OCT2 G808T基因突变可能与婴幼儿患者万古霉素的稳态谷浓度及临床疗效相关。     

降低万古霉素发酵生产成本的措施

通过采取国产原材料替代进口原材料以及降低进口原材料使用比例等多项措施,使万古霉素最终生产成本降低了61．1％,提高了公司经济效益。     

A Bioglass-Based Antibiotic (Vancomycin) Releasing Bone Void Filling Putty to Treat Osteomyelitis and Aid Bone Healing

While the infection rate after primary total joint replacements (TJR) sits at 1–2%, for trauma-related surgery, it can be as high as 3.6 to 21.2% based on the type of trauma; the risk of reinfection after revision surgery is even higher. Current treatments with antibiotic-releasing PMMA-based bone cement/ beads and/or systemic antibiotic after surgical debridement do not provide effective treatment due to fluctuating antibiotic levels at the site of infection, leading to insufficient local antibiotic concentration. In addition, non-biodegradable PMMA does not support bone regrowth in the debrided void spaces and often must be removed in an additional surgery. Here, we report a bioactive glass or bioglass (BG) substrate-based biodegradable, easy to fabricate “press fitting” antibiotic-releasing bone void filling (ABVF-BG) putty to provide effective local antibiotic release at the site of infection along with support for bone regeneration. The ABVF-BG putty formulation had homogenously distributed BG particles, a porous structure, and showed putty-like ease of handling. Furthermore, the ABVF-BG putty demonstrated in vitro antibacterial activity for up to 6 weeks. Finally, the ABVF-BG putty was biodegradable in vivo and showed 100% bacterial eradication (as shown by bacterial cell counts) in the treatment group, which received ABVF-BG putty, compared to the infection control group, where all the rats had a high bacterial load (4.63 × 10⁶ ± 7.9 × 10⁵ CFU/gram bone) and sustained osteomyelitis. The ABVF-BG putty also supported bone growth in the void space as indicated by a combination of histology, µCT, and X-ray imaging. The potential for simultaneous infection treatment and bone healing using the developed BG-based ABVF-BG putty is promising as an alternative treatment option for osteomyelitis.     

Labeling and Characterization of Phenol-Containing Glycopeptides Using Chemoselective Probes with Isotope Tags

Secondary metabolites are structurally diverse natural products (NPs) and have been widely used for medical applications. Developing new tools to enrich NPs can be a promising solution to isolate novel NPs from the native and complex samples. Here, we developed native and deuterated chemoselective labeling probes to target phenol-containing glycopeptides by the ene-type labeling used in proteomic research. The clickable azido-linker was included for further biotin functionalization to facilitate the enrichment of labeled substrates. Afterward, our chemoselective method, in conjunction with LC-MS and MSn analysis, was demonstrated in bacterial cultures. A vancomycin-related phenol-containing glycopeptide was labeled and characterized by our labeling strategy, showing its potential in glycopeptide discovery in complex environments.     

Removal of vancomycin administered during dialysis by a high‐flux dialyzer

Introduction: Hemodialysis patients frequently receive vancomycin for treatment of gram‐positive bacterial infections. This drug is most conveniently administered in outpatient dialysis units during the hemodialysis treatment. However, there is a paucity of data on the removal of vancomycin by high‐flux polyamide dialyzers. Methods: This is a prospective crossover study in which seven uninfected chronic hemodialysis patients at three dialysis units received vancomycin 1 gram intravenously over one hour immediately after the dialysis treatment (Phase 1), and vancomycin 1.5 grams during the last hour of dialysis treatment using a polyarylethersulfone, polyvinylpyrrolidone, polyamide high‐flux (Polyflux 24R) dialyzer (Phase 2). There was a three‐week washout period between phases. Serial serum vancomycin concentrations were used to determine the removal of vancomycin when administered during dialysis. Findings: Dialysis removed 35 ± 15% (range 18‐56%) of the vancomycin dose when administered during the last hour of dialysis. The calculated area under the curve (AUC) of vancomycin levels for 0‐44.5 hours from the start of infusion were similar between the two phases (AUC_{Phase 1} 884 ± 124 mg‐hr/L, mean ± SD; AUC_{Phase 2} 856 ± 208 mg‐hr/L; P=0.72). Serum vancomycin concentrations immediately prior to the next dialysis treatment following vancomycin administration were also similar between the two phases (13.1 ± 2.7 mg/L in Phase 1 and 12.3 ± 3.3 mg/L in Phase 2; P=0.55). Discussion: When using a polyarylethersulfone, polyvinylpyrrolidone, and polyamide high‐flux HD membrane with a 24R Polyflux dialyzer, vancomycin can be administered during the last hour of dialysis if the dose that is prescribed for intra‐dialysis dosing is empirically increased to account for intra‐dialytic drug removal.     

超高效液相色谱-串联质谱法快速测定动物源食品中万古霉素残留量

提供一种利用超高效液相色谱-串联质谱（ultra-high performance liquid chromatography-tandem mass spectrometry,UPLC-MS/MS）法快速测定动物源性食品中万古霉素残留量的方法。冻猪背膘、冻猪去骨前腿皮和 冻猪去骨前腿肉样品用0.1%甲酸水溶液-乙腈溶液（90∶10,V/V）提取,所得提取液用水饱和正己烷除脂、MCX 固相萃取柱净化,净化液经氮吹浓缩、流动相定容后用UPLC-MS/MS仪测定。结果表明：在2.0～100.0 μg/L质 量浓度范围内,万古霉素的线性关系良好,R2＞0.999 9;该方法的最低检出限为0.3 μg/kg,定量限为1.0 μg/kg; 在10.0、20.0、50.0、100.0 μg/kg 4 个添加水平下,3 种样品中万古霉素的回收率为70.05%～102.97%,相对标准偏 差≤4.65%。该方法有效解决了样品基质效应大、灵敏度低等问题,能够保证分析结果的准确性,适用于动物源性 食品,尤其是高脂肪含量的动物源性食品中万古霉素的残留量测定。     

探讨万古霉素硫酸钙联合超短波治疗创伤性骨髓炎临床疗效及安全性

目的: 探讨万古霉素硫酸钙联合超短波治疗创伤性骨髓炎临床疗效及安全性。方法: 74例创伤性骨髓炎患者随机分为对照组（37例）与试验组（37例）,2组均给予常规治疗以及对症治疗,手术前3 d给予注射用盐酸去甲万古霉素0.8 g/d静滴,每日2次,选取硫酸钙骨移植替代物5～10 g与盐酸去甲万古霉素1 g加水调制成糊状,术后给予注射用盐酸去甲万古霉素0.8 g/d,每日2次,试验组术后联合超短波治疗,2组患者一个周期均为28 d,共治疗2个周期。比较2组临床疗效、治疗前后血液流变学指标、血清C 反应蛋白（CRP）、血清肿瘤坏死因子（TNF-α）、核因子-κB(NF-κB）以及不良反应发生情况。结果: 治疗后,对照组临床总有效率为78.38%,显著低于试验组的97.30% (P<0.05)。治疗后,试验组的红细胞聚集指数高于对照组（P<0.05）,血浆粘度、全血粘度、红细胞沉降率（ESR）水平低于对照组（P<0.05）。试验组血清CRP、TNF-α、NF-κB水平显著低于对照组 (P<0.05)。对照组不良反应发生率为13.51%,试验组为8.11%,差异无统计学意义(P＞0.05)。结论: 万古霉素硫酸钙联合超短波治疗创伤性骨髓炎的临床疗效显著,安全性高。     

Rice hull smoke extract inactivates Salmonella Typhimurium in laboratory media and protects infected mice against mortality

A previously characterized rice hull smoke extract (RHSE) was tested for bactericidal activity against Salmonella Typhimurium using the disc-diffusion method. The minimum inhibitory concentration (MIC) value of RHSE was 0.822% (v/v). The in vivo antibacterial activity of RHSE (1.0%, v/v) was also examined in a Salmonella-infected Balb/c mouse model. Mice infected with a sublethal dose of the pathogens were administered intraperitoneally a 1.0% solution of RHSE at four 12-h intervals during the 48-h experimental period. The results showed that RHSE inhibited bacterial growth by 59.4%, 51.4%, 39.6%, and 28.3% compared to 78.7%, 64.6%, 59.2%, and 43.2% inhibition with the medicinal antibiotic vancomycin (20 mg/mL). By contrast, 4 consecutive administrations at 12-h intervals elicited the most effective antibacterial effect of 75.0% and 85.5% growth reduction of the bacteria by RHSE and vancomycin, respectively. The combination of RHSE and vancomycin acted synergistically against the pathogen. The inclusion of RHSE (1.0% v/w) as part of a standard mouse diet fed for 2 wk decreased mortality of 10 mice infected with lethal doses of the Salmonella. Photomicrographs of histological changes in liver tissues show that RHSE also protected the liver against Salmonella-induced pathological necrosis lesions. These beneficial results suggest that the RHSE has the potential to complement wood-derived smokes as antimicrobial flavor formulations for application to human foods and animal feeds. PRACTICAL APPLICATION: The new antimicrobial and anti-inflammatory rice hull derived liquid smoke has the potential to complement widely used wood-derived liquid smokes as an antimicrobial flavor and health-promoting formulation for application to foods.