中国科技论文统计源期刊　中文核心期刊  
美国《化学文摘》《国际药学文摘》
《乌利希期刊指南》
WHO《西太平洋地区医学索引》来源期刊  
日本科学技术振兴机构数据库（JST）
第七届湖北十大名刊提名奖  
医药导报
医药导报, 2019, 38(1): 103-106
doi: 10.3870/j.issn.1004-0781.2019.01.024
重症血流感染患者药学监护
杨霞, 魏春燕, 徐珽
四川大学华西医院临床药学部,成都 610041
通信作者 徐珽(1973-),男,重庆人,主任药师,硕士生导师,研究方向:临床药学、医院药学。电话:028-85422664,E-mail:tingx2009@163.com。

作者简介 杨霞(1990-),女,四川成都人,药师,硕士,从事临床药学工作。ORCID:0000-0001-6170-3293。E-mail:1142513284@qq.com。
中图分类号: R978;R969.3     文献标识码: B     文章编号: 1004-0781(2019)01-0103-04
摘要:

目的 探讨临床药师在重症血流感染患者个体化治疗中的作用。方法 临床药师参与1例耐药人葡萄球菌及头状葡萄球菌解脲亚种血流感染患者的抗感染治疗。监测万古霉素血药浓度,并行抗感染疗效评价、不良反应监测、肾功能监测等药学监护。通过查阅指南和国内外文献,建议临床医师调整万古霉素剂量。结果 医师采纳临床药师建议,患者病情好转且及时逆转万古霉素不良反应,患者于第31天出院。结论 临床药师参与重症血流感染抗感染治疗过程,结合相关指南、文献以及病原学检查、血药浓度监测等结果,协助医师及时优化用药方案,在保证抗感染治疗效果的同时,预防和减少了药物不良反应的发生。
关键词: 万古霉素 ; 血药浓度 ; 临床药师 ; 感染

Abstract:

万古霉素(vancomycin)为糖肽类抗菌药物,临床用于治疗革兰阳性菌特别是耐甲氧西林金黄色葡萄球菌(methicillin-resistant Staphylococcus aureus,MRSA)导致的感染,是目前治疗MRSA的首选药物[1]。重症监护病房(intensive care unit,ICU)患者机体状态差,合并多种疾病,呼吸和循环系统不稳定,多器官功能不全,免疫系统受损,低蛋白血症,血液透析治疗及并用多种药物等,由于复杂因素存在,导致万古霉素在ICU患者的药动学和药效学等方面均发生较大改变[2,3]。万古霉素治疗窗较窄,容易导致肾毒性、耳毒性等不良反应。因此,对ICU使用万古霉素的患者进行治疗药物监测(therapeutic drug monitoring,TDM)、不良反应监测等药学服务,具有重要的临床意义。笔者介绍临床药师对1例重症血流感染患者进行的药学服务。

1 病例资料

患者,男,20岁6个月,体质量90 kg,因“头痛伴意识障碍5 h 余”入院。2017年8月7日15:00左右,患者突发头痛,平躺休息10 min后意识模糊逐渐加深。呼之不应,伴喷射样呕吐,呕吐物为胃内容物。患者被立即送至我院急诊科,急诊行CT头部血管三维重建增强扫描提示:脑室大量积血,蛛网膜下腔少许积血?脑实质肿胀,中线结构居中,颅骨未见确切骨折。

左侧侧脑室后角内前份积血内见大小约2.3 cm×1.6 cm的混杂稍高密度影,计算机断层摄影血管造影术(computed tomographic angiography,CTA)提示:双侧椎动脉迂曲,右侧椎动脉较细,右侧大脑前动脉中段局部管腔稍增宽,左侧大脑后动脉中段以远血管显示不清,左侧大脑中动脉远段分支血管较对侧略减少,余颅内大动脉及其分支血管未见确切狭窄或扩张。初步诊断为:左侧脑出血破入脑室;左侧丘脑占位:性质待排。2017年8月8日患者急诊全麻下行“左侧大脑后动脉血栓性动脉瘤切除术+血管成形术+脑室造瘘术+颅内血肿清除术+颅内减压术+窦修补术+去骨瓣减压术”,术后患者转入我院ICU。

患者平素身体健康,无肝炎及结核病史,无吸烟饮酒史,无食物药物过敏史。

入院体检:体温38 ℃,脉搏79次·min-1,呼吸率20次·min-1,血压119/74 mmHg(1 mmHg=0.133 kPa)。营养发育良好,皮肤及淋巴结未见异常,头部外观未见明显异常,胸部未见明显异常,腹部未见明显异常,脊柱四肢未见明显异常。专科体检:患者呈昏迷状态,双侧瞳孔等大等圆,直径2 mm,对光反射消失。

2 结果与分析
2.1 治疗经过

入院第2天(2017年8月8日)患者昏睡,体温持续升高且超过38 ℃,考虑可能是中枢性高热引起,给予冰毯物理降温、冬眠合剂药物降温后体温仍较高。2017年8月10纤支镜下取得痰涂片结果示:少量革兰阴性(G-)杆菌,少量革兰阳性(G+)链球菌,且纤支镜吸出黄色脓性痰液增加,白细胞15.68×109·L-1,中性粒细胞比例90%,胸部X线检查提示:右肺中下野炎症。在药敏试验结果未明确的情况,临床药师与医师共同制定初始治疗方案:采用哌拉西林钠/他唑巴坦静脉滴注,4.5 g,q8h。

入院第7天(2017年8月13日),患者冰毯控温,最高体温38.6 ℃。17:05患者心率快,血压低,多巴胺11 μg·min-1·kg-1血压控制在约110/46 mmHg,持续高热,呛咳反射明显,气管导管吸出大量黄色脓痰,考虑感染性休克可能性较大。当日患者白细胞数9.94×109·L-1,PCT 0.55 ng·mL-1,CRP 83.5 mg·L-1,血培养结果示:人葡萄球菌及头状葡萄球菌解脲亚种,对苯唑西林耐药,对万古霉素敏感。患者肌酐74 μmol·L-1,肾小球滤过率126.22 mL·min-1·(1.72 m2)-1。医师决定采用静脉滴注万古霉素1 g,q12h,抗感染治疗。

入院第11天(2017年8月18日)患者最高体温38.2 ℃,万古霉素谷血药浓度3.3 μg·mL-1,8月15日肌酐68 μmol·L-1,肾小球滤过率130.69 mL·min-1·(1.72 m2)-1,根据美国感染病协会(Infectious Diseases Society of America,IDSA)万古霉素用药指南[4]推荐,临床药师建议调整万古霉素剂量为1 g,q8h。医师认为该剂量风险较大,还有待商榷,单独追加一剂万古霉素。

入院第13天(2017年8月20日)测得肌酐66 μmol·L-1,肾小球滤过率132.3 mL·min-1·(1.72 m2)-1,白细胞13.25×109·L-1,中性粒细胞百分比84%,PCT 0.21 ng·mL-1。

入院第16天(2017年8月23日)患者最高体温39 ℃,万古霉素谷血药浓度4.3 μg·mL-1。临床药师再次建议调整万古霉素剂量为1 g,q8h,医师采纳建议,于8月24日调整万古霉素用药剂量,并密切监测肾功能指标及万古霉素血药浓度。

入院第18天(2017年8月25日)患者最高体温38.2 ℃,无自主睁眼及遵嘱行为,采用持续冰毯及冬眠合剂降温。白细胞计数:14.43×109·L-1,中性粒细胞数0.58×109·L-1,中性粒细胞百分率79%;PCT 0.13 ng·mL-1,CRP 111 mg·L-1,IL-6 43.23 pg·mL-1;肌酐61 μmol·L-1,eGFR 136.65 mL·min-1·(1.72 m2)-1。万古霉素谷血药浓度3.2 μg·mL-1。临床药师建议继续观察病情变化。

入院第21天(2017年8月28日)患者最高体温38 ℃,PCT 0.13 ng·mL-1,CRP 71.5 mg·L-1,IL-6 18.84 pg·mL-1;白细胞10.65×109·L-1,中性粒细胞数7.67×109·L-1,中性粒细胞百分比72%;肌酐118 μmol·L-1,eGFR 76.07 mL·min-1·(1.72 m2)-1。万古霉素谷血药浓度25.5 μg·mL-1。经过万古霉素剂量调整,血药浓度升高,患者症状明显改善,体温及各炎性指标明显下降。考虑到患者血药浓度超过目标值,且肌酐水平明显升高,临床药师与医师商议调整万古霉素剂量为1 g,q12h。

入院第29天(2017年9月4日),患者最高体温38.1 ℃,白细胞计数4.7×109·L-1,中性粒细胞百分率73.2%,PCT 0.14 ng·mL-1,CRP 23.5 mg·L-1,肌酐57 μmol·L-1,肾小球滤过率141.51 mL·min-1 ·(1.72 m2)-1。患者临床症状明显好转,有自主睁眼动作,遵嘱活动,停用万古霉素。

入院第31天(2017年9月6日),患者情况较前明显好转,家属要求回当地医院继续治疗。

3 讨论
3.1 初始抗感染治疗

患者持续高热,白细胞15.68×109·L-1,中性粒细胞百分比90%,胸部X线检查提示:右肺中下野炎症。纤支镜吸出黄色脓性痰液增加,且痰涂片示:G-杆菌,少量G+链球菌,考虑医院获得性肺炎可能性大。《抗菌药物临床应用指导原则》指出:早发医院获得性肺炎(入院时间>2 d~<5 d)病原体多为敏感菌,预后较好,可能的病原均为主要为肺炎链球菌、流感嗜血杆菌、甲氧西林敏感的金黄色葡萄球菌以及大肠埃希菌、肺炎克雷伯菌、肠杆菌属等[5]。患者为青壮年男性,无基础疾病史,且90 d内无抗菌药物用药史,可经验性的选用β-内酰胺类抗菌药物(头孢曲松、哌拉西林钠/他唑巴坦、头孢哌酮钠/舒巴坦),喹诺酮类药物(环丙沙星、莫西沙星)。

3.2 抗感染治疗方案的调整

3.2.1 万古霉素初始剂量确定 患者接受哌拉西林钠他唑巴坦治疗3 d,感染持续加重,且发生感染性休克。结合血培养结果及药敏试验,临床药师与医师商议加用万古霉素抗感染治疗。

万古霉素临床应用中国专家共识(2011年版)指出:肾功能正常的成人,万古霉素常规剂量为1 g,q12h[1]。抗微生物治疗指南(热病46版)[6]中指出,肾功能正常患者(肌酐清除率>90 mL·min-1,万古霉素的用量为1 g,q12h。《万古霉素临床应用中国专家共识》[1]指出:对于病情严重患者,可考虑给予25~30 mg·kg-1负荷剂量(根据实际体质量),使万古霉素尽快达到有效谷浓度。临床医生经验性采用1 g,q12h剂量静脉滴注万古霉素。

3.2.2 万古霉素血药浓度、不良反应监护及剂量调整 早期因万古霉素纯度较低,不良反应较多,上市初期临床常规进行TDM,但随着万古霉素纯度提高,目前万古霉素剂量与血药浓度的线性关系已经明确,肾功能正常患者不需常规进行TDM,但对于特殊人群也需进行TDM监测 [1,7]。美国感染病学会(IDSA)和美国卫生系统药师协会( AmericanSocietyof Health-SystemPharmacists,ASHP)推荐常规做TDM适应证患者:①应用大剂量万古霉素并且使用疗程较长的患者;②肾功能不稳定(如明显恶化或明显改善)的患者;③联合使用其他耳、肾毒性的患者;④新生儿、儿童及老人。患者肾功能正常,采用常规剂量,因此未行TDM。

患者使用万古霉素多日,仍持续高热且炎性指标未降低。IDSA指出 [8]严重金黄色葡萄球菌感染治疗成败与万古霉素血药浓度的高低有关。从万古霉素治疗的有效性考虑,严重感染患者推荐万古霉素谷血药浓度维持在15~20 mg· L - 1 [ 1 ] ,临床药师考虑患者抗感染效果不佳,可能是万古霉素血药浓度未达目标水平,建议医师万古霉素用药前30 min抽血检测其谷血药浓度。万古霉素血药浓度结果3.2 mg·L-1,远低于目标水平。临床药师建议将万古霉素调整为1 g,q8h,医师考虑该剂量风险较大,当日单独追加万古霉素1 g。患者持续高热,炎症指标高于正常水平,第2次检测到万古霉素血药浓度仍低于5 mg·L-1。临床药师再次建议调整万古霉素剂量,医师予以采纳,同时密切监测肾功能指标及万古霉素血药浓度。

万古霉素常见的不良反应是肾功能损伤,其发生率1%~5%。近年来研究发现,常规用量15~20 mg·kg-1导致肾功能损伤少见,临床每日用量超过4g会导致肾功能损伤增加[9]。万古霉素治疗窗和中毒窗较窄,通过临床观察和研究显示万古霉素血药谷浓度升高与肾毒性发生有着明显的相关性,万古霉素血药浓度≥15 mg·L-1是肾毒性发生的独立危险因素[10,11]。然而有研究表明万古霉素谷浓度≥15 mg·L-1和万古霉素血药浓度<15 mg·L-1对患者预后无影响 [12,13]。万古霉素引起的肾毒性与多种因素有关,有研究表明,万古霉素肾毒性的发生率与联用血管升压药、利尿药、氨基苷类抗菌药物等药物,合并恶心肿瘤、糖尿病及患者年龄、体质量、体质状况等相关[14,15]。近年来,越来越多的研究表明哌拉西林钠他唑巴坦联合万古霉素更容易引起急性肾功能损伤。研究指出,相比于单独使用或联合头孢吡肟,万古霉素联合哌拉西林他唑巴坦引起急性肾功能损伤的风险更大[16,17,18]。MCQUEEN等[19]研究指出,万古霉素联用哌拉西林钠他唑巴坦较单用万古霉素潜在的肾毒性更大,对于重症监护室患者血药浓度>15 mg·L-1,万古霉素和哌拉西林钠他唑巴坦联合使用肾毒性增加的危险因素,不排除伴随的肾毒性药物的使用。调整万古霉素剂量后患者血药浓度超过目标血药浓度,同时联合哌拉西林钠他唑巴坦、去甲肾上腺素、多巴胺等,以上因素均是导致其肾功能指标肌酐清除率显著下降的原因。及时调整万古霉素剂量后,血药浓度低于目标水平,肌酐清除率也恢复正常水平,以上结果表明万古霉素引起的肾功能损伤可能与万古霉素血药浓度正相关。

4 结束语

临床药师全程参与该患者抗感染方案的制定与药学监护,根据临床症状建议监测万古霉素血药浓度,并根据万古霉素血药浓度提醒临床医生调整万古霉素剂量,同时密切检测炎症相关指标及肾功能指标,及时发现万古霉素引起的肾功能损伤,提醒临床医生调整万古霉素剂量。临床药师积极参与临床合理用药,并根据患者情况提供个体化的给药方案,及时发现药物相关不良反应,保障药物治疗的安全性和有效性。建议:(1)对于超重患者考虑给予负荷剂量,缩短万古霉素血药浓度达谷浓度时间。(2)对于以下几类病患积极监测万古霉素血药浓度:①重症监护室患者;②体质量异常(消瘦或肥胖)患者;③对于同时联用哌拉西林钠他唑巴坦、去甲肾上腺素、多巴胺、呋塞米等药物的患者,积极监测肾功能指标,以便调整万古霉素剂量并及时发现肾功能损伤,保证重症患者抗感染治疗方案安全有效。

The authors have declared that no competing interests exist.
参考文献
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正万古霉素(vancomycin)已问世半个多世纪了,随着其临床应用的日益广泛,人们对该药的认识也日益加深。近年来在医院感染中,革兰阳性菌的比例呈上升趋势,特别是耐甲氧西林葡萄球菌(MRS)的感染更加引人瞩目,其治疗也颇为棘手。众所周知,万古霉素至今依然是治疗
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[3] 董芊汝,赵夕岚,翟所迪.重症监护病房患者万古霉素治疗药物监测的系统评价[J].中国临床药理学杂志,2015,31(13):1358-1360.
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[4] RYBAK M J,LOMAESTRO B M,ROTSCHAFER J C,et al.Vancomycin therapeutic guidelines:a summary of consensus recommendations from the infectious diseases Society of America,the American Society of Health-System Pharmacists,and the Society of Infectious Diseases Pharmacists[J].Clin Infect Dis,2009,49(3):325-327.
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[5] 钟南山,万希润,马小军,等.国家卫生计生委印发抗菌药物临床应用指导原则(2015年版)[J].中国医药生物技术,2015,(5):477.
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[6] 范洪伟,吕伟,王焕玲,等.桑福德抗微生物治疗指南 [M].新译45版.北京:中国协和医药大学出版社,2017:220.
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[7] 何志超,伍俊妍,邱凯锋.万古霉素个体化给药临床药师指引[J].今日药学,2015,25(2):78-82.
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[8] LIU C,BAYER A,COSGROVE S E,et al.Clinical practice guidelines by the infectious diseases society of america for the treatment of methicillin-resistant Staphylococcus aureus infections in adults and children[J].Clin Infect Dis,2011,52(3):e18-55.
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[9] LODISET P,LOMAESTRO B,GRAVES J,et al.Larger va-ncomycin doses(at least four grams per day)are associated with an increased incidence of nephrotoxicity[J].Antimicrob Agents Chemother,2008,52(4):1330-1336.
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[10] BOSSO J A,NAPPI J,RUDISILL C,et al.Relationship bet-ween vancomycin trough concentrations and nephrotoxicity:a prospective multicenter trial[J].Antimicrob Agents Chemother,2011,55(12):5475-5479.
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[11] VAN H S J,PATERSON D L,LODISE T P.Systematic review and meta-analysis of vancomycin-induced nephrotoxicity associated with dosing schedules that maintain troughs between 15 and 20 milligrams per liter[J].Antimicrob Agents Chemother,2013,57(2):734-744.
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[12] CLEMENS E C,CHAN J D,LYNCH J B,et al.Relation-ships between vancomycin minimum inhibitory concentration,dosing strategies,and outcomes in methicillin-resistant Staphylococcus aureus bacteremia[J].Diagn Micr Infe,2011,71(4):408-414.
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[13] PRYBYLSKI J P.Vancomycin trough concentration as a predictor of clinical outcomes in patients with Staphylococcus aureus bacteremia:a Meta-analysis of observational sStudies[J].Pharmacotherapy,2015,35(10):889-898.
Study Objective To determine the strength of evidence for better clinical outcomes in patients with Staphylococcus aureus bacteremia who had vancomycin trough levels of 15–2002mg/L. Design Meta-analysis of 14 observational cohort studies. Patients A total of 1677 patients, representing geriatric and unspecified inpatients, who received standard dosing of vancomycin for the treatment of S.02aureus bacteremia and who had trough level goals of 15–2002mg/L. Measurements and Main Results The treatment variables examined in the analysis were vancomycin trough concentrations and 24-hour area under the concentration-time curve to minimum inhibitory concentration ratio (AUC:MIC) values. The outcomes of interest were mortality, persistent bacteremia, and treatment failure. Mortality was defined as 30-day mortality, in-hospital mortality, or a comparable measure; persistent bacteremia was defined as bacteremia lasting at least 702days after the initiation of vancomycin; treatment failure was defined as a composite end point that included at least persistent bacteremia and mortality, as previously defined. Higher vancomycin trough levels (1502mg/L or greater or based on MIC) were not associated with significantly reduced treatment failure, persistent bacteremia, or mortality. Higher AUC:MIC values were associated with significantly reduced treatment failure (odds ratio [OR] 0.41, 95% confidence interval [CI] 0.31–0.53), persistent bacteremia (OR 0.53, 95% CI 0.33–0.86), and mortality (OR 0.47, 95% CI 0.33–0.65). The weighted mean02±02SD AUC:MIC threshold defined by regression analyses in the included studies was 41802±028802hours, which supports the current goal of 40002hours or more. Conclusion Vancomycin trough concentrations do not have sufficient evidence to support their use as the primary guide in vancomycin dosing. Dosing should instead focus on AUC:MIC values, which have strong evidence of benefit.
DOI:10.1002/phar.1638      PMID:26497475      URL    
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[14] 蔡云东,费爱华.万古霉素血药浓度监测和肾毒性及临床疗效关系的研究[J].现代中西医结合杂志,2016,25(29):3199-3201,3299.
目的 探讨万古霉素血药浓度与肾毒性之间的关系,对患者预后的影响及增加肾毒性的危险因素。方法 选择符合标准的住院期间静脉用万古霉素且监测血药浓度的患者105例,收集患者性别、年龄、感染部位、科室分布情况、病原学检查情况等资料,统计万古霉素谷浓度、峰浓度及不同谷浓度下肾毒性发生率;根据万古霉素用药期间是否出现肾毒性分为肾损伤组与非损伤组,比较2组万古霉素谷浓度、峰浓度,用药前后血肌酐值、肌酐清除率,合并疾病情况,同时使用抗生素及其他药物情况。结果 105例患者共行血药浓度监测125例次,谷浓度〈20 mg/L与≥20 mg/L的肾毒性发生率分别为7.57%和46.15%,二者比较差异有统计学意义（P〈0.05）。肾损伤组的谷浓度中位数达26.1 mg/L,非损伤组中位数13.2 mg/L,肾损伤组明显高于非损伤组（P〈0.05）;肾损伤组合并糖尿病比例和使用升压药比例均明显高于非损伤组（P均〈0.05）。革兰阳性菌感染者40例经万古霉素治疗后,临床有效率为57.5%;细菌学清除率32.5%,未清除率20%,病原菌转为革兰阴性菌3例,未复查16例。结论 高的万古霉素谷浓度可增加肾毒性的风险,谷浓度≥20mg/L肾毒性发生率明显增加;若患者合并糖尿病或使用升压药,将增加肾毒性的风险。
DOI:10.3969/j.issn.1008-8849.2016.29.003      URL    
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[15] MINEJIMA E,CHOI J,BERINGER P,et al.Applying new diagnostic criteria for acute kidney injury to facilitate early identification of nephrotoxicity in vancomycin-treated patients[J].Antimicrob Agents Chemother,2011,55(7):3278-3283.
Acute kidney injury (AKI) associated with high-dose vancomycin (VAN) therapy is a clinical concern, but no uniform diagnostic criteria exist. The AKI Network (AKIN) proposed new criteria to diagnose AKI based on abrupt changes in serum creatinine or urine output. We conducted a prospective observational study to determine the incidence and severity of AKI and associated outcomes using the AKIN criteria versus traditional definitions. Eligible patients (n = 227) were elderly (median, 70 years) and received VAN therapy for 8 days (median). AKI occurred in 43 patients (19%) using AKIN criteria at an onset of 6 days. AKI incidence was similar for patients with a trough level of 15 (24%; 17/72) versus <15 (17%; 26/155) g/ml. Compared to non-AKI patients, more AKI patients resided in the intensive care unit (ICU) (47% [20/43] versus 27% [50/184]; P = 0.017), had a prior AKI episode (19% [8/43] versus 7% [5/184]; P = 0.001), and received vasopressor (28% [12/43] versus 14% [25/184]; P = 0.04) and/or nephrotoxins (84% [36/43] versus 67% [123/184]; P = 0.04). Seventeen of the AKI patients met traditional criteria, of whom more patients had stage 2 and 3 AKI (76% versus 8%; P = 0.0001), dosage adjustment (41% versus 15%) and renal consultation (35% versus 12%), prolonged length of stay after AKI (11 versus 7.5 days) and died (29% versus 12%) than those diagnosed by AKIN criteria (P value not significant). Use of AKIN criteria for AKI has the potential to improve care of VAN-treated patients by facilitating early detection of AKI and warrants confirmation in large prospective trials.
DOI:10.1128/AAC.00173-11      PMID:3122454      URL    
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[16] NAVALKELE B,POGUE J M,KARINO S,et al.Risk of acute kidney injury in patients on concomitant vancomycin and piperacillin-tazobactam compared to those on vancomycin and cefepime[J].Clin Infect Dis,2017,64(2):116-123.
Abstract Background: Recent evidence suggests that among patients receiving vancomycin, receipt of concomitant piperacillin-tazobactam increases the risk of nephrotoxicity. Well-controlled, adequately powered studies comparing rates of acute kidney injury (AKI) among patients receiving vancomycin + piperacillin-tazobactam (VPT) compared to similar patients receiving vancomycin + cefepime (VC) are lacking. In this study we compared the incidence of AKI among patients receiving combination therapy with VPT to a matched group receiving VC. Methods: A retrospective, matched, cohort study was performed. Patients were eligible if they received combination therapy for 48 hours. Patients were excluded if their baseline serum creatinine was >1.2mg/dL or they were receiving renal replacement therapy. Patients receiving VC were matched to patients receiving VPT based on severity of illness, intensive care unit status, duration of combination therapy, vancomycin dose, and number of concomitant nephrotoxins. The primary outcome was the incidence of AKI. Multivariate modeling was performed using Cox proportional hazards. Results: A total of 558 patients were included. AKI rates were significantly higher in the VPT group than the VC group (81/279 [29%] vs 31/279 [11%]). In multivariate analysis, therapy with VPT was an independent predictor for AKI (hazard ratio = 4.27; 95% confidence interval, 2.73-6.68). Among patients who developed AKI, the median onset was more rapid in the VPT group compared to the VC group (3 vs 5 days P =< .0001). Conclusion: The VPT combination was associated with both an increased AKI risk and a more rapid onset of AKI compared to the VC combination.
DOI:10.1093/cid/ciw709      PMID:27986669      URL    
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[17] HAMMOND D A,SMITH M N,LI C,et al.Systematic revi-ew and Meta-analysis of acute kidney injury associated with concomitant vancomycin and piperacillin/tazobactam[J].Clin Infect Dis,2017,64(5):666-674.
Concomitant vancomycin and piperacillin/tazobactam may be associated with increased acute kidney injury (AKI) compared to vancomycin without piperacillin/tazobactam. A systematic search of Medline, Cochrane Library, and Scopus through October 2016 using ["vancomycin" and "piperacillin" and "tazobactam"] and ["AKI" or "acute renal failure" or "nephrotoxicity"] and registered meta-analysis (PROSPERO: CRD42016041646) with relevant scenarios was performed. From 307 results, fourteen observational studies totaling 3549 patients were analyzed. Concomitant vancomycin and piperacillin/tazobactam was associated with AKI in unadjusted (odds ratio (OR) 3.12, 95% confidence interval (CI) 2.04-4.78) and adjusted (aOR 3.11, 95% CI 1.77-5.47) analyses. Similar findings were seen assessing studies in adults (aOR 3.15, 95% CI 1.72-5.76), children (OR 4.55, 95% CI 2.71-10.21), and when <50% of patients received care in an intensive care unit (aOR 3.04, 95% CI 1.49-6.22) but not 50% (aOR 2.83, 95% CI 0.74-10.85). Increased AKI with concomitant vancomycin and piperacillin/tazobactam should be considered when determining beta-lactam therapy.
DOI:10.1093/cid/ciw811      PMID:27940946      URL    
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[18] RINDONE J P,MELLEN C,RYBA J.Does piperacillin-ta-zobactam increase the risk of nephrotoxicity when used with vancomycin:a Meta-analysis of observational trials[J].Curr Drug Saf,2017,12(1):62-66.
Background: Observational studies have suggested an increased risk of nephrotoxicity when piperacillin-tazobactam is added to vancomycin, although the data are confliciting. <br/> Objective: To perform a meta-analysis of identified studies to assess if adding piperacillin-tazobactam to vancomycin increases the incidence of nephrotoxicity. <br/> Method: A systematic review of PubMed, EMBASE, Cochrane Central, and Google Scholar was conducted to identify studies. Studies selected for meta-analysis were full length reports, retrospective or prospective, and designed specifically to assess if the combining piperacillin-tazobactam with vancomycin increases nephrotoxicity. <br/> Results: Six observational trials involving 963 patients were identified and analyzed. Five trials were retrospective and one was prospective. Vancomycin/piperacillin-tazobactam was compared to vancomycin alone in 2 trials, to vancomycin/cefepime in 3 trials, and vancomycin/cefepime or meropenem in one. Meta-analysis showed a statistical increase in the incidence of nephrotoxicity when piperacillin-tazobactam/vancomycin is compared to the control group (2.26 95% CI 1.41-3.63, p= 0.0007). No differences were noted between groups in patients requiring renal replacement. <br/> Conclusion: Adding piperacillin-tazobactam to vancomycin increases the risk of nephrotoxicity when compared to vancomycin alone or vancomycin with either cefepime or meropenem.
DOI:10.2174/1574886311666161024164859      PMID:27784223      URL    
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[19] MCQUEEN K E,CLARK D W.Does combination therapy with vancomycin and piperacillin-tazobactam increase the risk of nephrotoxicity versus vancomycin alone in pediatric oatients?[J].J Pediatr Pharmacol Ther,2016,21(4):332-338.
react-text: 209 The aminoglycosides have long been effective antibiotics in treatment of serious gram-negative infections. However, ototoxicity and nephrotoxicity have been of major concern because of the narrow therapeutic range of these agents and the wide variability in pharmacokinetics among patients. With recent advances in aminoglycoside monitoring techniques, the risk of toxicity has been greatly... /react-text react-text: 210 /react-text [Show full abstract]
DOI:10.5863/1551-6776-21.4.332      PMID:27713673      URL    
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关键词（key words）
万古霉素
血药浓度
临床药师
感染
作者
杨霞
魏春燕
徐珽