万古霉素不同输注时长对重症感染患者血药浓度、疗效及预后影响的研究

目的比较万古霉素不同静脉输注时长对重症感染患者的血药浓度、疗效和预后的影响,并寻找血药浓度影响因素。方法对2015年7月至2018年1月在蚌埠医学院第一附属医院重症监护病房(ICU)使用万古霉素的61例重症感染患者,随机分为Nh静脉滴注(未规定输注时间)组和1 h、3 h静脉泵入组,了解万古霉素习惯性输注时间及血药浓度,并分析比较1 h、3 h静脉泵入组的万古霉素谷浓度、疗效和预后的差异,并使用倾向性匹配筛选验证。最后将所有患者纳入线性回归,分析影响谷浓度的因素。结果万古霉素Nh组的血药浓度为(8.74±6.36)μg/mL。1 h比3 h输注万古霉素谷浓度高[(17.84±14.26)μg/mL,(11.18±7.26)μg/mL]。疗效中1 h组体温较3 h组下降明显,但两组预后差异无统计学意义。回归分析显示年龄、万古霉素使用之前肌酐和尿素氮、谷浓度尿素氮、机械通气时间、万古霉素使用时间是万古霉素谷浓度的影响因素。结论 1 h比3 h内静脉输注万古霉素血药浓度更高,能够达到指南推荐目标谷浓度区间,缩短了治疗时间,并且在控制患者体温方面也有优势,故1 h输注万古霉素是较为合适的选择。年龄、基础肌酐和尿素氮、机械通气时间、万古霉素使用时间是血药浓度的影响因素。     

万古霉素曲线下面积的列线图预测重症患者万古霉素相关肾损伤的临床应用价值

目的:探讨万古霉素曲线下面积（AUC）的列线图预测重症患者万古霉素相关肾损伤的临床应用价值。方法:采用回顾性队列研究的方法,纳入2015年1月至2017年12月入住东南大学附属中大医院重症医学科接受经静脉使用万古霉素治疗的重症患者。收集万古霉素治疗开始时患者的临床特征及血药浓度达到稳定状态时的药代动力学参数（包括谷浓度...     

老年重症感染患者肾功能与万古霉素血药浓度的相关性

目的分析老年重症感染患者肾功能与万古霉素血药浓度的相关性。方法选择80例重症感染老年患者为研究对象,均经验性使用万古霉素抗感染治疗,治疗期间检测血药浓度及肾功能,根据相关指标将患者分为肾功能正常组与肾功能减退组,比较两组血清万古霉素谷浓度检出情况,比较不同血药浓度患者血清肾功能〔尿素氮(BUN)、血清肌酐(Scr)及内生肌酐清除率(Ccr)〕,经相关性分析找出老年重症感染患者肾功能与万古霉素血药浓度的相关性。结果80例老年重症感染患者中肾功能正常者42例,其他38例均为肾功能减退。万古霉素血清谷浓度共检测136次,其中肾功能正常组检测71次,肾功能减退组检测65次。肾功能减退组万古霉素血清谷浓度低谷浓度、中谷浓度检出次数均较肾功能正常组显著减少,高谷浓度检出次数较肾功能正常组显著升高,差异有统计学意义(P<0.05)。肾功能正常组万古霉素平均谷浓度明显低于肾功能减退组,差异有统计学意义(P<0.05)。随着万古霉素血清谷浓度升高,老年重症感染患者血清BUN、Scr水平升高,Ccr水平降低,差异有统计学意义(P<0.05)。老年重症感染患者血清BUN、Scr水平与万古霉素血药浓度呈正相关(r=0.377、0.630,均P<0.05),与Ccr呈负相关(r=-0.297,P<0.05)。结论老年重症感染患者万古霉素的血药浓度直接影响其肾功能,药物在使用期间应谨慎,医务工作者可动态监测患者血药浓度及肾功能相关指标水平变化情况,及时对给药方案做出合理调整,实现个体化给药,以降低肾毒性,增加治疗安全性。     

肺部真菌感染患者伏立康唑血药浓度监测的临床应用

目的 通过监测肺部真菌感染患者伏立康唑的血药浓度,探讨伏立康唑血药浓度与临床疗效和不良反应的相关性以及在不同病区的特点.方法 采用高效液相色谱法一荧光法测定伏立康唑血药浓度,观察不同病区肺部真菌感染患者在治疗期间的临床疗效和不良反应发生的情况.结果 共纳入87例患者,伏立康唑血药浓度检测次数为133次,87例患者首次检测的血药浓度为(3.37±2.6) mg/L,133次检测的血药浓度为(2.98±2.28) mg/L;静脉治疗时血药浓度(3.30±2.61) mg/L,口服治疗时血药浓度为(2.31±2.02) mg/L,静脉治疗的血药浓度显著高于口服治疗的血药浓度(P=0.018);门诊患者血药浓度为(3.06±2.2) mg/L,普通病区患者血药浓度为(2.6±2.5) mg/L,ICU患者血药浓度为(3.1±2.5)mg/L,三组间差异无统计学意义,但对于同一患者而言,门诊患者药物浓度波动幅度较小,ICU患者血药浓度波动幅度较大.87例患者中,68例治疗成功(78％),19例治疗失败(22％),比较治疗成功组和失败组伏立康唑血药浓度,两组差异无统计学意义,提示血药浓度与疗效无明显相关性,但在治疗失败组中,血药浓度低于1 mg/L的比例明显高于治疗成功组,两组差异有统计学意义(36.8％ vs 14.7％,P=0.048).87例患者中,低钾血症发生率为32％,肝功能受损为14％,肾功能受损为3.4％,皮疹为3.4％,视觉障碍为2％.其中,视觉障碍和肝功能受损发生率与血药浓度有关系(均P＜0.05).结论 伏立康唑血药浓度波动范围大,平均血药浓度为(3.37±2.6) mg/L.血药浓度与临床疗效无明显相关性,但血药浓度低于1 mg/L,治疗失败率可能增加;神经系统的不良反应和肝功能受损与较高的血药浓度有关;建议治疗期间血药浓度维持在(1～5) mg/L.在使用伏立康唑时,不同来源的患者应监测其血药浓度,尤其是ICU患者,应加强血药浓度的监测,及时调整用药方案,以减少药物不良反应.     

145例肺结核患者利福平血药浓度监测分析

利福平(rifampicin ,RFP)是主要抗结核药物,个体血药浓度差异较大,尤其在肝脏损伤的结核病患者中更为明显。以往经验剂量已较难反映其临床疗效。因此,对该药血药浓度的监测具有重要意义。现将我院1999一2003年145例住院肺结核患者的利福平血药浓度监测情况做回顾性总结分析。     

新生儿和婴儿先天性心脏病术后万古霉素低谷浓度发生状况分析△

目的了解新生儿和婴儿先天性心脏病外科手术后万古霉素血清谷浓度偏低发生状况并探讨其相关因素。方法利用医院信息系统收集2017年1月至2018年6月广东省人民医院收治的月龄不大于6个月,先天性心脏病手术后接受了万古霉素治疗并监测了万古霉素稳态谷浓度≥1次患儿的病历资料进行回顾性分析。收集患儿一般情况,稳态血清谷浓度,使用万古霉素前及使用期间血肌酐浓度,手术情况等资料进行统计分析。结果纳入分析的患者39例,检测次数为41例次;日龄(75.51±44.06)d,体质量(4.15±1.07)kg。2组患儿的性别、日龄、体质量,万古霉素使用前和使用期间血肌酐浓度比较,差异均无统计学意义(P0.05);低浓度组与达标浓度组患儿万古霉素血清谷浓度比较,差异有统计学意义[(6.15±2.30)μg/mL vs.(15.92±3.52)μg/mL,t=-10.759,P=0.000)]。结论婴儿先天性心脏病术后万古霉素血清谷浓度偏低的发生率为63.4%,应注意监测万古霉素血清谷浓度。     

145例肺结核患者利福平血药浓度监测分析

利福平（rifampicin ,RFP）是主要抗结核药物,个体血药浓度差异较大,尤其在肝脏损伤的结核病患者中更为明显.以往经验剂量已较难反映其临床疗效.因此,对该药血药浓度的监测具有重要意义.现将我院1999-2003年145例住院肺结核患者的利福平血药浓度监测情况做回顾性总结分析.     

315例吡嗪酰胺血药浓度监测结果分析

目的分析吡嗪酰胺血药浓度监测结果,指导临床合理用药。方法采用回顾性分析的方法,收集我院2013年9月至2014年10月315例肺结核住院患者吡嗪酰胺的血药浓度检测结果,采用SPSS 18.0软件进行统计学分析,计量资料采用t检验,计数资料采用χ2检验,以P0.05为差异有统计学意义。结果(1)315例结核病患者中,低于正常浓度11.7%(37/315),正常浓度46.7%(147/315),高于正常浓度45.2%(131/315)(2)男性血药浓度及每千克体质量剂量分别为(17.54±5.80)mg/L、(24.99±3.17)mg/kg,明显低于女性[分别为(23.38±8.22)mg/L、(29.03±4.50)mg/kg],差异有统计学意义(t值分别为-6.586、-8.002,P值分别为0.000、0.000)(3)不同年龄段患者的血药浓度无统计学差异(F=1.237,P=0.296)。结论加强血药浓度监测,实现合理用药。     

快速康复外科护理对食管癌围术期患者的临床疗效

目的分析快速康复外科护理对食管癌围术期患者的临床疗效。方法选取2018年南京医科大学附属淮安第一医院收治的食管癌围术期患者86例,根据计算机随机分组分为对照组和试验组,每组43例。对照组患者采用常规护理,试验组患者给予快速康复外科护理。比较两组患者首次排气时间、静脉输液时间、首次进食时间、术后住院时间及住院费用。结果试验组患者首次排气时间、静脉输液时间、首次进食时间、术后住院时间均短于对照组,住院费用少于对照组(P0.05)。结论快速康复外科护理可有效缩短食管癌围术期患者术后排气时间、静脉输液时间、进食时间、住院时间,减少住院费用。     

老年人地高辛用量的探讨

目的 探讨老年病人使用地高辛的最佳剂量。方法 对我院近11年来进行的1584例次老年病人地高辛血药浓度监测结果进行分析。结果 在使用地高辛常规治疗剂量时，老年患者地高辛中毒发生率明显高于青年患者。结论 老年人在使用地高辛治疗时，建议从小剂量开始，0．0625mg，1—2次／d；在使用过程中，应当常规进行地高辛血药浓度监测，以作为用药参考；但是不应片面依赖地高辛血药浓度监测结果，尤其不能仅仅根据地高辛血药浓度来简单判断中毒还是剂量不足；更重要的是结合临床症状，以达到用药的个体化，减少毒副反应，提高治疗效果。     

Simple approach to improving vancomycin dosing in intensive care: a standardised loading dose results in earlier therapeutic levels

Background: Patients in the Intensive Care Unit (ICU) often have sub‐therapeutic vancomycin levels in the initial stages of therapy. Loading doses have been demonstrated to overcome this problem. Aim: The aim of this study was to determine the impact of a standardised loading dose and increased clinician awareness of under‐dosing on the achievement of early therapeutic vancomycin trough concentrations in the ICU. Methods: A pre‐ and post‐intervention observational study was conducted in the ICU following the introduction of a 2‐g vancomycin loading dose and demonstration of local under‐dosing. All initial vancomycin trough levels were examined, except those from neurosurgical patients. Primary outcome measures were the proportion of patients achieving therapeutic vancomycin levels and mean trough concentrations. A year after introduction, a review was conducted to further assess the impact and sustainability of the intervention. Results: There were 31 courses of vancomycin in the pre‐intervention period (no loading doses given) and 21 courses in the post‐intervention period, of which 11 had a loading dose. In the pre‐intervention group, 13% of courses achieved therapeutic concentrations. This increased to 33% in the post‐intervention group (P= 0.08). A statistically significant increase in mean trough concentration, from 9.8 ± 6.6 mg/L to 14.9 ± 6.3 mg/L (P= 0.01), between the pre‐ and post‐intervention groups was observed. During the follow‐up period, results were similar to the post‐intervention audit. Conclusion: A standardised loading dose is a simple and sustainable intervention that may improve early achievement of therapeutic vancomycin levels in critically ill patients. The clinical significance of this requires further study.     

High-dose vancomycin therapy for methicillin-resistant Staphylococcus aureus infections: efficacy and toxicity

BACKGROUND: Vancomycin hydrochloride treatment failure for infections caused by susceptible methicillin-resistant Staphylococcus aureus (MRSA) strains with high minimum inhibitory concentration (MIC) has prompted recent guidelines to recommend a higher vancomycin target trough of 15 to 20 microg/mL. METHODS: A prospective cohort study of adult patients infected with MRSA was performed to determine the distribution of vancomycin MIC and treatment outcomes with vancomycin doses targeting an unbound trough of at least 4 times the MIC. The microbiology laboratory computer records were used to identify all patients from whom MRSA was isolated from August 1, 2004, through June 30, 2005. Primary outcome measures were clinical response, mortality, and nephrotoxicity. Patients were placed into subgroups based on target trough attainment and high vs low vancomycin MIC (>/=2 vs <2 microg/mL) for efficacy and high vs low trough (>/=15 vs <15 microg/mL) for nephrotoxicity analyses. RESULTS: Of the 95 patients in the study, 51 (54%) were infected with high-MIC strains and had pneumonia (77%) and/or bacteremia. An initial response rate of 74% was achieved if the target trough was attained irrespective of MIC. However, despite achieving the target trough, the high-MIC group had lower end-of-treatment responses (24/39 [62%] vs 34/40 [85%]; P = .02) and higher infection-related mortality (11/51 [24%] vs 4/44 [10%]; P=.16) compared with the low-MIC group. High MIC (P = .03) and Acute Physiology and Chronic Health Evaluation II score (P = .009) were independent predictors of poor response in multivariate analysis. Nephrotoxicity occurred only in the high-trough group (11/63 [12%]), significantly predicted by concomitant therapy with other nephrotoxic agents. CONCLUSIONS: High prevalence of clinical MRSA strains with elevated vancomycin MIC (2 microg/mL) requires aggressive empirical vancomycin dosing to achieve a trough greater than 15 microg/mL. Combination or alternative therapy should be considered for invasive infections caused by these strains.     

Vancomycin: the need to suit serum concentrations in hemodialysis patients

The vancomycin dose for hemodialysis (HD) patients should be adjusted by monitoring drug serum concentrations. However, this procedure is not available in most health services in Brazil, which usually adopts protocols based on published studies. The trials available are controversial, and several have not been conducted with current dialyzers. This study aimed at assessing the suitability of vancomycin serum concentrations in HD patients at a public hospital. Blood samples of HD patients were collected from November 2006 to May 2007, at time intervals of 48, 96, 120, or 168 hours after vancomycin administration. Drug measurement was performed with polarized light immunofluorescence. Approximately 86% of trough vancomycin serum concentrations were below the recommended value, indicating exposure to subtherapeutic doses and a higher risk for selecting resistant microorganisms.     

Comparative effects of amlodipine and nifedipine GITS during treatment and after missing two doses

OBJECTIVE: To compare the antihypertensive efficacy of amlodipine and nifedipine gastrointestinal therapeutic system (GITS) measured by office and ambulatory blood pressure monitoring (ABPM) during treatment and, after patients have missed two doses. METHOD: After a single blind run-in 4-week placebo period, 58 patients were randomly allocated to amlodipine (5mg/daily, n=30) or nifedipine GITS (30mg/daily; n=28) in a double-blind, double dummy fashion. Patients received active medication for 4 weeks. Then, to simulate failure of compliance, patients received two single blinded doses of placebo. Ambulatory blood pressure monitoring was carried out at the end of run-in placebo phase, the first day, the last day of active treatment and up to 72h after the last active dose. RESULTS: Diastolic blood pressure was controlled in 61.9% patients on amlodipine and 52.9% on nifedipine GITS. Reductions in blood pressure were similar in both groups. ABPM showed significant reduction in blood pressure from the first day in the nifedipine GITS group, while amlodipine group had marginal effect. Peak reduction in systolic/diastolic blood pressure was 26/15mmHg at 5-6h after ingestion of amlodipine tablets. The trough reduction was 22/13mmHg; with a trough-to-peak ratio of 84.61% for systolic and 86.67% for diastolic blood pressure. Peak reduction in systolic/diastolic blood pressure with nifedipine GITS was 19/15mmHg and the trough reduction was 21/17mmHg, giving a trough-to-peak ratio of 100% for both systolic and diastolic blood pressure. When patients received placebo after 4 weeks of active treatment, simulating a compliance failure, amlodipine maintained reduction in systolic and diastolic blood pressure for at least up to 72h after the last active dose, maintaining 57.71% of the effect for systolic blood pressure and 60.00% for diastolic blood pressure. In contrast, nifedipine GITS effect was rapidly lost during this study phase, with a reduction in systolic and diastolic blood pressure of only 14-16%, 72h after the last active dose. CONCLUSION: This study showed that amlodipine and nifedipine GITS reduce blood pressure to about the same extent during chronic treatment. In the case of compliance failure, such as missing one or two doses, amlodipine maintained significant and important antihypertensive effect with the trough-to-peak ratio still over 50% 72h after the last active dose. On the other hand, the coverage of nifedipine GITS was limited to about 36h after the last active dose.     

Predictors of mortality for methicillin-resistant Staphylococcus aureus health-care-associated pneumonia: specific evaluation of vancomycin pharmacokinetic indices

OBJECTIVE: The goal of this investigation was to determine whether vancomycin pharmacokinetic indexes (eg, serum trough concentrations or area under the concentration curve [AUC] values) were associated with mortality for patients with health-care-associated pneumonia (HCAP) attributed to methicillin-resistant Staphylococcus aureus (MRSA). DESIGN: A retrospective, single-center, observational cohort study. SETTING: Barnes-Jewish Hospital, a 1,200-bed urban teaching facility. PATIENTS: Adult patients requiring hospitalization who were identified as having HCAP attributed to MRSA by BAL semi-quantitative cultures. INTERVENTIONS: Retrospective data collection from automated hospital, microbiology, and pharmacy databases. MEASUREMENTS AND MAIN RESULTS: One hundred two patients with MRSA HCAP were identified over a 6.5-year period. Thirty-two patients (31.4%) died during their hospitalization. The mean (+/- SD) vancomycin trough concentrations (13.6 +/- 5.9 vs 13.9 +/- 6.7 microg/mL, respectively; p = 0.866) and AUC values (351 +/- 143 vs 354 +/- 109 microg/h/mL, respectively; p = 0.941) did not differ between survivors and nonsurvivors. The stratification of the vancomycin trough concentrations and AUC values yielded no relationship with hospital mortality. CONCLUSIONS: We found no evidence that greater vancomycin trough concentrations or AUC values correlated with hospital outcome. Based on these results, aggressive dosing strategies for vancomycin (eg, trough concentrations of > 15 microg/mL) may not offer any advantage over traditional dose targets (range, 5 to 15 microg/mL).     

Relationship of serum antibiotic concentrations to nephrotoxicity in cancer patients receiving concurrent aminoglycoside and vancomycin therapy

Methicillin-resistant coagulase-negative staphylococci have become increasingly responsible for febrile episodes in cancer patients, often necessitating the addition of vancomycin to an aminoglycoside-containing broad-spectrum antibiotic regimen. A total of 229 courses of antibiotic therapy in 229 patients were evaluated for nephrotoxicity associated with the administration of an aminoglycoside and/or vancomycin. The incidence of nephrotoxicity observed in patients administered an aminoglycoside (Group A) was 18 percent; vancomycin (Group B) 15 percent; and an aminoglycoside concurrently with vancomycin (Group C) 15 percent. The following pharmacokinetic/dosing factors were significantly associated with increased nephrotoxicity in the groups: baseline serum creatinine level, mean daily dose during the first three days of therapy (Group B), and elevated serum trough aminoglycoside or vancomycin concentrations (2 micrograms/ml or more or 10 micrograms/ml or more, respectively). No cumulative nephrotoxicity was demonstrated with the concurrent administration of vancomycin and an aminoglycoside. A higher incidence of nephrotoxicity was seen in Group C (42 percent) and Group B (27 percent) patients, in whom trough serum vancomycin concentrations were 10 micrograms/ml or more.     

Errors in trough: peak ratio determinations induced by patient behaviour

BACKGROUND: Trough: peak ratio is often used to evaluate the duration of antihypertensive action. Whatever the method of measurement chosen, trough effect has to be measured 24 h after the last drug intake for a once daily regimen. Peak effect is usually measured 4-6 h after drug intake. If patients' compliance to therapeutic instructions is perfect, then the 'intrinsic' trough: peak ratio of the drug is equal to the measured trough: peak ratio. Some patients do not follow these instructions, leading to biases in the evaluation of the ratio. For trough evaluation, all patients (N) are supposed to take the last dose of the drug the day before blood pressure measurement. However, if some patients (n1) wrongly take the drug in the morning of the visit, they will be evaluated at peak (type A error). For peak evaluation, all patients (N) are supposed to take the drug a few hours before blood pressure measurement. If some patients (n2) miss their morning dose, they will be evaluated at trough (type B error). METHODS: In the MACH 1 study, the use of an electronic pill count monitor allowed us to quantify n1/N and n2/N. A total of 452 hypertensive patients were randomly assigned to two groups. Patients in group 1 received written instructions to take their last dose during the morning of the day before the visit, whereas patients of group 2 had to take their last dose on the morning of the visit. RESULTS: Electronic pill-box recording revealed that 32.9%: of patients in group 1 committed type A error, whereas 27.7% of patients in group 2 committed type B error. The resulting 'pill-box corrected' trough: peak ratio was lower (87.5% for diastolic blood pressure and 93.1% for systolic blood pressure) than the uncorrected trough: peak ratio (95.2% for diastolic blood pressure and 96.0% for systolic blood pressure) of the population. CONCLUSION: The random behaviour of patients, with respect to treatment compliance, results in a systematic overestimation of the measured trough: peak ratio. The computation of this ratio may be optimized by improving patient compliance. Alternatively, only data from a patient subpopulation that complies with the therapeutic protocol, as reported by readings from electronic pill boxes, should be taken into account for its calculation.     

How vancomycin is used in Australasia – A survey

Background: Vancomycin serum concentrations have been monitored over the last 30 years in an attempt to avoid dose-dependent toxicity and enhance efficacy. Current literature recommendations for peak and trough concentrations are usually in the range of 20–40 mg/L and 5–10 mg/L, respectively. Literature recommendations regarding the time at which peak concentrations are measured are highly variable, ranging from immediately after the end of the infusion to three hours post-dose. Aims: To identify how vancomycin dosing is being monitored and assess variability in the current practice. Methods: A survey of microbiology departments and infectious disease physicians in major Australasian hospitals was undertaken. The variability in the current practice was assessed by fitting mean recommendations to a two compartment Bayesian model. Results: Of the 83 (70%) who replied 71 (86%) monitored vancomycin concentrations. Fifty-four percent targeted peak concentrations within the range of 20–40 mg/L, and 73% targeted trough concentrations ≤ 10 mg/L. The time of sampling of peak concentrations varied considerably ranging from immediately (12%) to 120 minutes (12%) post-infusion (median 30 minutes [40%]). The concentration-time curves resulting from three sets of mean recommendations (“peaks' drawn at: 0, 30 and 120 minutes aiming for a concentration of 35 mg/L with a trough concentration of 10 mg/L) were modelled using a two compartment Bayesian programme. The predicted true peak (maximum) concentrations ranged from 30 to 86 mg/L, despite aiming for identical target concentrations, indicating marked variation in the actual dosing practice. Conclusions: There is thus considerable variation in the practice of vancomycin therapeutic monitoring which has a major effect on dosing. The main contributing factor is the variable timing of sampling peak concentrations. (Aust NZ J Med 1993; 23: 662–666.)