Study of the pharmacokinetics of vancomycin in patients with impaired liver function

Infections caused by methicillin-resistant Staphylococcus aureus pose a serious problem postoperatively. Patients with hepatic dysfunction can be considered to be more susceptible to infection. Since little is known about the effects of the severity of hepatic dysfunction on the pharmacokinetics of vancomycin, we studied the pharmacokinetics of vancomycin in preoperative patients with hepatic dysfunction, after the intravenous infusion of 500 mg. In patients with liver disease and normal renal function, an enhancement of renal clearance caused by a reduction in percent protein binding was canceled out by a reduction in non-renal clearance caused by liver dysfunction, resulting in liver disease having no effect on the total clearance of the drug. In patients with impaired liver and renal functions and/or obstructive jaundice, the unbound fraction of vancomycin increased, whereas the renal excretion of vancomycin was delayed. It should be noted that an excessive increase in blood vancomycin concentration may be brought about even with a conventional dose in patients with hepatic dysfunction. Received: December 1, 1998 / Accepted: December 9, 1998     

Prospective, double-blind, randomized trial of teicoplanin versus vancomycin for the therapy of vascular access-associated bacteremia caused by gram-positive pathogens

Received: October 7, 1998 / Accepted: August 2, 1999     

Glycopeptide susceptibility profiles of nosocomial multiresistant Staphylococcus haemolyticus isolates

We investigated 48 Staphylococcus haemolyticus isolates from patients and medical staff in terms of susceptibility to and in-vitro selection for vancomycin and teicoplanin in regard to their antibiotypes. On comparison of multiresistant S. haemolyticus isolates with non-multiresistant isolates, the geometric mean minimum inhibitory concentration (MIC) of vancomycin for multiresistant S. haemolyticus was 2.9 μg/ml, and that of teicoplanin was 18.0 μg/ml, both of which values were significantly greater than the corresponding mean MICs of vancomycin (2.0 μg/ml) and teicoplanin (4.7 μg/ml) for nonmultiresistant isolates. After agar selection, the mean of the highest teicoplanin concentration of selected plates for multiresistant S. haemolyticus was 97.1 μg/ml, which was significantly higher than that for nonmultiresistant isolates (57.8 μg/ml). However, the means' of the highest vancomycin concentrations after agar selection for multiresistant and nonmulti-resistant isolates were the same, at 7.4 μg/ml, with no colonies capable of growing in 32 μg/ml of vancomycin. There was no significant difference in glycopeptide susceptibility between oxacillin-resistant and oxacillin-susceptible isolates among nonmultiresistant S. haemolyticus. The geometric mean MICs of vancomycin for oxacillin-resistant and oxacillin-susceptible isolates were 2.1 μg/ml and 1.6 μg/ml, and those of teicoplanin were 4.4 μg/ml and 5.6 μg/ml, while the means of the highest concentrations of the selected plates of vancomycin were 8.6 μg/ml and 3.3 μg/ml, and those of teicoplanin were 52.8 μg/ml and 74.7 μg/ml, respectively. Multiresistant isolates showed significantly greater mean MICs of vancomycin and teicoplanin and higher teicoplanin concentration of the selected plates than nonmultiresistant isolates, irrespective of oxacillin resistance. These results indicate that methicillin resistance may not be related to reduced susceptibility to glycopeptide in S. haemolyticus, and that a multiresistant profile is associated more with a decreasing susceptibility to glycopeptides then with resistance to oxacillin. In this study, antibiotypes showed good concordance with pulsed-field gel electrophoresis typing results, with a sufficiently high discriminatory ability index, of 0.912. We consider that primary screening with antimicrobial susceptibility testing and antibiotyping, with attention to the multiresistant profile, would be useful for monitoring nosocomial S. haemolyticus colonization and infection. Received: August 9, 2000 / Accepted: February 5, 2001     

国产替考拉宁对耐甲氧西林表皮葡萄球菌的体外抗菌活性观察

评价国产替考拉宁对耐甲氧西林表皮葡萄球菌（MRSE）和甲氧西林敏感表皮葡萄球菌（MSSE）的体外抗菌活性，用琼脂二倍稀释法测定了84株MRSE和28株MSSE临床菌株的最低抑菌浓度，并与万古霉素进行了比较，结果表明国产替考拉宁对48株MRSE和28株MSSE抑菌效果较好，其敏感率分别为97．62％和100％。     

反相高效液相色谱法测定人血浆中万古霉素浓度

目的　建立测定人血浆中万古霉素浓度的高效液相色谱方法。方法　采用HypersilC18柱( 4 0mm× 2 5 0mm ,5 μm)流动相为甲醇∶水 ( 2 0∶80 )含 0 1%三乙胺和 1%四氢呋喃 ,检测波长 2 30nm。结果　本方法线性范围 0 4～ 10 0 μg/ml,最低检测限 80ng/ml ,血浆平均回收率 10 0 2 % ,日内、日间RSD均小于10 %。结论　本方法简单快捷、灵敏度高、色谱效果好、结果准确 ,可用于万古霉素血浓度监测及体内药物动力学研究。     

群体药代动力学软件对肾功能亢进与非亢进骨科术后患者万古霉素谷浓度、AUC0 ~ 24 h的预测分析

目的：探讨群体药代动力学软件对肾功能亢进（ARC）和非亢进（non-ARC）骨科术后患者的万古霉素谷浓度、24 h药时曲线下面积（AUC0 ~24 h）的预测效果。方法：收集我院2018年1月 ～ 2022年12月骨科术后使用万古霉素的患者，通过HIS系统收集患者的基本信息、万古霉素峰谷浓度、血常规和生化指标等，计算患者肌酐清除率，并分为ARC组和non-ARC组。采用万古霉素剂量推荐和血药浓度预测系统、SmartDose软件回顾性预测患者的万古霉素谷浓度，采用SmartDose和JPKD软件预测万古霉素的AUC0 ~ 24 h。结果：与non-ARC组相比，ARC组患者年龄较小，血肌酐、血尿素、胱抑素C水平明显降低，而肌酐清除率较高（P ＜ 0.05）。与non-ARC组相比，ARC组患者谷浓度及AUC0 ~ 24 h均明显降低（P ＜ 0.05）。万古霉素剂量推荐和血药浓度预测系统和SmartDose软件对ARC与non-ARC骨科术后患者谷浓度预测的绝对权重偏差＞ 30%。JPKD软件对ARC与non-ARC骨科术后患者AUC0 ~ 24 h的绝对权重偏差＜ 30%且组内相关系数均＞ 0.750。结论：万古霉素剂量推荐和血药浓度预测系统和SmartDose软件预测ARC和non-ARC骨科术后患者万古霉素谷浓度效果欠佳，而JPKD软件较SmartDose软件更适用于预测AUC0 ~ 24 h。     

Vancomycin-Associated Nephrotoxicity: Grave Concern or Death by Character Assassination?

Vancomycin-associated nephrotoxicity was reported in 0% to 5% of patients in the 1980s. This has been confirmed by numerous clinical trials comparing novel anti-methicillin-resistant Staphylococcus aureus agents with vancomycin at the Food and Drug Administration-approved dosage of 1 g every 12 hours. Treatment failures of vancomycin in patients with methicillin-resistant S. aureus infections have been reported despite in vitro susceptibility. These failures have led to the use of vancomycin doses higher than those approved by the Food and Drug Administration. Higher doses are being administered to achieve goal vancomycin trough concentrations of 10 to 20 μg/mL recommended by several clinical practice guidelines endorsed by the Infectious Diseases Society of America. Recent studies suggest that increased rates of nephrotoxicity are associated with aggressive vancomycin dosing. These increased rates are confounded by concomitant nephrotoxins, renal insufficiency, or changing hemodynamics. These studies also have demonstrated that vancomycin's nephrotoxicity risk is minimal in patients without risk factors for nephrotoxicity. Clinicians unwilling to dose vancomycin in accordance with clinical practice guidelines should use an alternative agent because inadequate dosing increases the likelihood of selecting heteroresistant methicillin-resistant S. aureus isolates.     

Impact of patient characteristics and infection type on clinical outcomes of patients who received linezolid or vancomycin for complicated skin and skin structure infections caused by methicillin-resistant Staphylococcus aureus: a pooled data analysis

Phase III randomized, clinical trials are primarily designed to evaluate overall treatment-outcome comparisons. Although valuable data are gained from such comparisons, it is difficult to draw meaningful inferences about potential outcomes differences in specific patient groups and infection types. It is well established that clinical outcomes are dependent on host, treatment- and pathogen-related factors and understanding which groups benefit from one treatment relative to another is of great importance. This study sought to determine if clinical success in the treatment of complicated skin and skin structure infections (cSSSI) caused by methicillin resistant Staphylocccus aureus (MRSA) with linezolid or vancomycin varied across subpopulations and infection type. Data from 3 prospective, randomized trials evaluating linezolid and vancomycin for the treatment of MRSA cSSSI were pooled. Treatment related differences in outcomes were found, on both the absolute and relative scales, for most subpopulations and infection types. Identifying treatment differences in outcome by patient subpopulation can enhance clinical decision making.     

Is prediffusion test an alternative to improve accuracy in screening hVISA strains and to detect susceptibility to glycopeptides/lipopeptides?

The characterization of heteroresistant vancomycin-intermediate Staphylococcus aureus strains (hVISA) is even more challenging, as no routine standardized laboratory methods are available. A total of 124 S. aureus isolates recovered from inpatients attended in hospitals of Santa Catarina State, Southern Brazil, were evaluated. The MIC of vancomycin, teicoplanin, and daptomycin was determined by Etest and prediffusion tests using NeoSensitabs® tablets. All isolates were susceptible to vancomycin (MICs: 0.5–3 μg/mL) by Etest. However, according to prediffusion test, 17 isolates presented reduced susceptibility to vancomycin, and of these, 12 were confirmed as hVISA using populational analysis. Considering daptomycin, prediffusion results were in agreement with susceptibility data (MICs), as all isolates were susceptible. Considering that characterizing hVISA is challenging and that MIC determination is not adequate to characterize this phenotype, prediffusion test was a viable alternative to screening hVISA and reduced susceptibility to vancomycin. It was simple and low cost, with accuracy comparable to other well-established methods.