清晨好,您是今天最早来到科研通的研友!由于当前在线用户较少,发布求助请尽量完整地填写文献信息,科研通机器人24小时在线,伴您科研之路漫漫前行!

Single- and multiple-dose pharmacokinetics and total removal of colistin in a patient with acute kidney injury undergoing extended daily dialysis

医学 粘菌素 透析 加药 肾功能 药代动力学 肾脏替代疗法 急性肾损伤 移植 重症监护医学 麻醉 抗生素 内科学 生物 微生物学
作者
A.-K. Strunk,Julius J. Schmidt,Eva Baroke,Stefanie M. Bode‐Böger,J. Martens-Lobenhoffer,Tobias Welte,Jan T. Kielstein
出处
期刊:Journal of Antimicrobial Chemotherapy [Oxford University Press]
卷期号:69 (7): 2008-2010 被引量:23
标识
DOI:10.1093/jac/dku075
摘要

Sir, The emergence of multidrug-resistant bacteria has recently renewed interest in colistin, which was first introduced in 1959. For intravenous administration, not colistin itself, but its inactive prodrug colistin methanesulfonate (CMS) is administered. As 70% of CMS is excreted unchanged in the urine, its t1 2 increases with a decline in glomerular filtration rate (GFR) to up to 14 h in patients with a GFR ,15 mL/min. Additionally, a larger fraction of the CMS dose is converted into colistin with decreasing renal function. Thus, dose reduction is recommended with decreasing GFR. Data from 1968 on four patients treated with twice-weekly dialysis for 11–16 h using a cuprophane membrane are the foundation for current dosing regimens in chronic haemodialysis. In these patients a dose of 1 million units every 48 h is recommended. Data on dosing in critically ill patients undergoing extended dialysis are missing. We here report for the first time, singleand multiple-dose pharmacokinetics of colistin in a critically ill patient undergoing extended dialysis. Written informed consent was obtained from the patient’s mother for publication of this study. Ethical approval for reporting this case was obtained from the Medical School Hannover. A patient aged between 30 and 40 years (height 163 cm, weight 53 kg) was admitted to our intensive care unit (ICU) for rapidly progressive respiratory failure. The patient had undergone lung transplantation for pulmonary hypertension 10 months earlier. The patient’s post-transplant course had been complicated by acute rejection and an Aspergillus fumigatus infection. On admission, the patient required non-invasive ventilation. Bronchoalveolar lavage revealed a multiresistant Klebsiella pneumoniae in addition to the previously known Aspergillus. Endotracheal intubation was required owing to worsening respiratory failure. Extended dialysis for acute kidney injury was started. As the K. pneumoniae was only susceptible to colistin, we initiated treatment with 3 million units every 8 h after an initial dose of 6 million units. Blood samples were taken at regular intervals on day 1 and day 9 of treatment. Colistin and CMS concentrations were determined separately by HPLC combined with tandem mass spectrometry, as recently used in its modified form. The average dialysis time between day 1 and day 9 was 552 min; mean blood and dialysate flow were 191 mL/min and 121 mL/ min, respectively. After a loading dose of 6 million units, peak levels of colistin and CMS were 10.01 mg/mL and 24.76 mg/mL, respectively. The lowest plasma concentrations on day 1 were 3.83 mg/mL for colistin and ,0.1 mg/mL for CMS. Extended dialysis with the above-mentioned specifications led to a reduction of peak colistin levels (Figure 1). After 9 days of treatment with 3 million units every 8 h there was neither an accumulation of colistin (peak level day 9: 8.96 mg/mL, trough level 2.13 mg/mL) nor an accumulation of CMS (peak level day 9: 11.83 mg/mL, trough level ,0.1 mg/mL). Depending on the blood and dialysate flow, the dialyser clearance of colistin ranged between 54 and 71 mL/min and the CMS clearance between 25 and 62 mL/min. The amount of colistin in the total collected dialysate was 245 mg on day 1 and 191 mg on day 9. Although the patient responded well to this antibiotic therapy, subsequent cerebral aspergillosis could not be treated, leading to the death of the patient after 5 weeks of treatment in the ICU. There are scarce data on the dosing of antibiotics in patients undergoing renal replacement therapy. Our data suggest that extended dialysis eliminates colistin effectively and to a larger extent than regular intermittent outpatient haemodialysis. This is in line with recent data on two critically ill patients undergoing a modern type of intermittent dialysis (1.6 m polymethylacrylate membrane, blood/dialysate flow 300/500 mL/min, duration 4 h), in whom a CMS dialyser clearance of 90 mL/min was reported. Li et al. described a dialyser clearance of 11.9 mL/min for colistin and 11.2 mL/min for CMS in one critically ill patient undergoing continuous venovenous haemodiafiltration, which due to its continuous mode would remove approximately the same amount of the drug. Lastly, dialyser clearance in five patients receiving continuous venovenous haemodiafiltration was recently reported to be 72 mL/min for colistin and 32 mL/min for CMS. Thus, dosing colistin as recommended during regular haemodialysis is inadequate and would result in a significant under-dosing, which could be associated with a substantial risk, especially in critically ill patients in the ICU. A dose of 3 million units every 8 h seems to be adequate for patients undergoing daily extended dialysis for 9 h a day with a high flux 1.3 m dialyser. This dose of 9 million units per day did not lead to accumulation of the drug.
最长约 10秒,即可获得该文献文件

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
沐浠完成签到 ,获得积分10
13秒前
葛力完成签到,获得积分20
17秒前
科研通AI2S应助葛力采纳,获得10
29秒前
30秒前
宇文非笑完成签到 ,获得积分0
38秒前
科研通AI5应助laodai8855采纳,获得20
39秒前
41秒前
乾坤侠客LW完成签到,获得积分10
1分钟前
1分钟前
lixuebin完成签到 ,获得积分10
2分钟前
科研通AI2S应助葛力采纳,获得10
2分钟前
lxh完成签到 ,获得积分10
2分钟前
2分钟前
2分钟前
laodai8855发布了新的文献求助20
2分钟前
3分钟前
3分钟前
科研通AI5应助梨子茶采纳,获得30
3分钟前
3分钟前
bju发布了新的文献求助10
3分钟前
3分钟前
科研通AI2S应助科研通管家采纳,获得10
3分钟前
搜集达人应助科研通管家采纳,获得10
3分钟前
科研通AI2S应助科研通管家采纳,获得10
3分钟前
bju完成签到,获得积分10
3分钟前
4分钟前
梨子茶发布了新的文献求助30
4分钟前
mczhu完成签到,获得积分10
4分钟前
聪慧芷巧完成签到 ,获得积分10
4分钟前
qqJing完成签到,获得积分10
4分钟前
deallyxyz应助草木采纳,获得10
4分钟前
5分钟前
5分钟前
常有李完成签到,获得积分10
5分钟前
5分钟前
默默孱完成签到 ,获得积分10
5分钟前
JamesPei应助汎影采纳,获得10
5分钟前
5分钟前
Lucas应助汎影采纳,获得10
5分钟前
wwe完成签到,获得积分10
5分钟前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Immigrant Incorporation in East Asian Democracies 600
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
不知道标题是什么 500
A Preliminary Study on Correlation Between Independent Components of Facial Thermal Images and Subjective Assessment of Chronic Stress 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3968504
求助须知:如何正确求助?哪些是违规求助? 3513318
关于积分的说明 11167279
捐赠科研通 3248691
什么是DOI,文献DOI怎么找? 1794414
邀请新用户注册赠送积分活动 875030
科研通“疑难数据库(出版商)”最低求助积分说明 804652