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, 2017, 36(6): 707-708
doi: 10.3870/j.issn.1004-0781.2017.06.028
1例嗜酒患者化脓性脑膜炎的药学监护
王海涛, 仵文英, 王娜, 刘娜, 余静洁

摘要:

目的 为临床药师参与化脓性脑膜炎治疗提供参考。方法 根据患者生活不良嗜好及临床表现,临床药师协助医师综合分析脑膜炎可能为单核细胞增生性李斯特菌感染,并制定个体化抗感染方案。结果 医生采纳药师建议,患者感染得到有效控制,治疗27 d后康复出院。结论 临床药师通过参与化脓性脑膜炎临床治疗,针对李斯特菌的治疗提供合理抗感染方案。

关键词: 临床药师 ; 脑膜炎 ; 化脓性 ; 李斯特菌

Abstract:

化脓性脑膜炎发病率为0.4%~6%,涉及到身体重要器官,如不及时治疗,可能造成严重后果。为尽快控制感染,应合理选择和使用抗菌药物。抗菌药物的选择,因每例患者的年龄和自身基本情况的不同而异。临床药师参与临床治疗,协助医生制定抗感染方案,提高治疗效果。

1 病例概况

患者,男,62岁,身高167 cm,体质量64 kg。患者4 d前无明显诱因出现轻微头痛,呈闷痛,可忍受,次日头痛加重,为全头痛,胀痛明显,伴发热,最高体温39.0 ℃,偶有干咳,伴恶心、呕吐。自服琥乙酰螺旋霉素(每次3粒,每天3次),症状无明显改善,遂就诊我院神经内科,2015年3月9日收住入院。体检:体温38.6 ℃,脉搏110次·min-1,呼吸22次·min-1,血压126/91 mmHg(1 mmHg=0.133 kPa)。脑CT提示:未见明显异常,双侧上颌窦、筛窦炎。患者入院后仍有发热、头痛剧烈、血常规指标升高,考虑颅内感染可能性大。当日16∶00行腰椎穿刺,脑脊液浑浊,压力为1.833 kPa。当天经验性使用头孢曲松2.0 g,iv,q12h。2015年3月9日脑脊液常规示:细胞总数1 191×106·L-1;白细胞计数1 124×106·L-1;脑脊液生化结果:蛋白0.75 g·L-1,糖2.91 mmol·L-1,氯122.4 mmol·L-1;抗结核抗体试验为阴性,新型隐球菌墨汁染色也为阴性。2015年3月11日神经内科医师经讨论后认为:根据脑脊液常规和生化等检查结果,考虑患者化脓性脑膜炎的可能性大,可联合万古霉素1.0 g,静脉滴注,q12h,抗感染治疗,覆盖常见的病原菌。患者治疗2 d后症状无明显改善,仍有发热、头痛,遂请临床药师会诊,调整抗感染方案。

2 临床药师会诊
2.1 会诊分析和建议

2015年3月12日脑脊液常规示:蛋白定性为弱阳性;细胞总数1 048×106·L-1;白细胞计数1 014×106·L-1;脑脊液生化示:蛋白0.78 g·L-1,糖1.08 mmol·L-1,氯111.4 mmol·L-1。临床药师根据检查结果、问诊、分析病例及查阅文献,认为目前患者临床体征,脑脊液细胞总数、白细胞计数、蛋白高,糖低,氯正常,化脓性脑膜炎可能性大,目前治疗效果不理想可能有几个原因,并建议如下。①目前抗感染方案没有覆盖到引起患者脑膜炎的病原菌。根据《热病》和IDSA相关指南[1-2],老年人、嗜酒者、有严重基础疾病者有感染单核细胞增生性李斯特菌(Listeria monocytogenes,Lm)的高危因素,需加用氨苄西林覆盖可能病原菌,所以建议加用氨苄西林2.0 g,iv,q4h。②流行病学调查显示,肺炎链球菌对青霉素、第3代头孢菌素和其他广谱β-内酰胺类抗菌药物敏感性降低的比例显著升高。由于药物敏感性改变和抗菌药物在脑脊液中增加达到足够浓度所固有的因素,经验性治疗化脓性脑膜炎时需联合使用万古霉素,并且万古霉素谷浓度需达到15~20 μg·mL-1。建议监测万古霉素血药浓度,并根据血药浓度调整万古霉素剂量和频次,同时监测患者肾功能。③患者为社区获得性脑膜炎,感染耐药的革兰阴性杆菌,如:铜绿假单胞菌、鲍曼不动杆菌等可能性较低,但不能完全排除,建议再使用头孢曲松2~3 d,如效果不理想可停用头孢曲松,换用美罗培南2.0 g,iv,q8h。该药容易引起中枢系统毒副作用,在使用过程中应密切观察中枢神经系统变化。④目前结核相关检查均为阴性,脑脊液的相关检查结果均不支持结核感染,所以结核性脑膜炎可能性较小,暂不进行抗结核治疗。如上述抗细菌感染方案治疗效果不佳,再考虑抗结核治疗。

2.2 会诊后调整抗感染方案

经临床药师会诊后,临床医师完全采纳临床药师的建议,联合使用氨苄西林。2015年3月13日患者万古霉素血药浓度测得谷浓度16.1 μg·mL-1,达到治疗脑膜炎所需的谷浓度,所以不需调整剂量和频次。2015年3月14日脑脊液培养结果回报为Lm,再次请药师会诊。药师认为目前诊断明确,脑脊液培养Lm,应为致病菌,建议从经验治疗转为目标治疗,停用头孢曲松和万古霉素,单用氨苄西林。

2.3 目标治疗后患者转归

采用上述治疗方案后3 d,患者体温恢复正常,症状明显改善;10 d后脑脊液糖指标恢复正常,20 d后脑脊液白细胞计数、分叶核百分比和蛋白恢复正常;2次脑脊液培养未见细菌生长。2015年4月5日患者康复出院。

3 讨论

化脓性脑膜炎是一种严重的、威胁生命的疾病。目前的指南推荐,一旦怀疑或确诊为化脓性脑膜炎,应尽快经验性使用抗菌药物。对于初始抗菌药物的选择是基于最可能引起社区获得性脑膜炎的病原菌,而病原菌则根据患者年龄、嗜好和临床情况会有所不同。待脑脊液培养和药敏结果出来后,则可以由经验治疗转为针对性治疗。

由于该患者为老年人,有每日饮酒的习惯。酒精损害健康并且可降低身体免疫力,增加嗜酒者对一些感染性疾病的敏感性,特别是化脓性脑膜炎。有文献报道嗜酒患者社区获得性脑膜炎病原菌前两位是肺炎链球菌和Lm [3],而老年人则为肺炎链球菌、脑膜炎球菌和Lm[4]。根据该患者临床症状、脑脊液生化和常规,初步诊断为化脓性脑膜炎,初始治疗方案治疗效果欠佳,请临床药师会诊。临床药师经过分析、讨论、查阅文献,建议使用氨苄西林覆盖可能病原菌、监测万古霉素血药浓度和必要时调整抗菌药物。患者的脑脊液生化、常规和培养结果明确该例患者为Lm脑膜炎。

Lm是一种革兰阳性、无芽孢杆菌,可在-4~50 ℃环境生长。广泛分布在植物、土壤和水面上,也存在于绿饲料、生活污水、屠宰场垃圾、人和动物的粪便中[5]。目前研究表明只有Lm对人类是致病菌。尽管这个经食物传播的细菌所导致的疾病并不常见,但往往有严重的后果,病死率约为17%[6]。Lm在多个国家曾爆发流行,感染途径是食用污染的食物,如:未灭菌的牛奶、污染的卷心菜等,或者是由母亲直接垂直传染。

健康成年人感染Lm脑膜炎概率较低,它的主要易患人群包括老年人、嗜酒者、新生儿等。临床医生在治疗社区获得性脑膜炎时,对于一些特殊病人,如老年人、嗜酒者等往往没有选择针对李斯特菌的抗菌药物,而常用来治疗化脓性脑膜炎的第3代头孢菌素(头孢曲松、头孢噻肟、头孢他啶)以及万古霉素均对Lm不敏感。IDSA(2004)指南和《热病》(43版)均推荐氨苄西林联合或不联合庆大霉素来治疗Lm脑膜炎[1-2]。如果患者对氨苄西林过敏,可考虑使用复方磺胺甲叮恶唑作为替代药物。该患者为嗜酒的老年化脓性脑膜炎,经验性治疗时,没有覆盖可能的病原菌Lm,而选择经验治疗药物头孢曲松联合万古霉素,导致治疗效果不佳。临床药师会诊后根据患者病情、年龄、不良嗜好等基本情况,推荐加用氨苄西林。患者确诊为Lm脑膜炎后,停用其他抗菌药物,单用氨苄西林治疗。氨苄西林为广谱的半合成青霉素,为时间依赖型抗生素,半衰期小于1 h,可透过炎性血脑屏障,为了使氨苄西林既能在脑脊液达到有效浓度,又能维持T>MIC,所以推荐剂量和频次为2.0 g,iv,q4h。Lm脑膜炎一般抗感染治疗疗程至少为21 d,该患者治疗27 d后康复出院。

在本案例中,临床药师运用专业知识,以抗菌药物合理选择为切入点,参与临床治疗方案的制订,提高患者治疗效果和临床抗菌药物合理应用。

The authors have declared that no competing interests exist.

参考文献

[1] SANFORD J P,范洪伟.热病:《桑福德抗微生物治疗指南》[M].43版.北京:中国协和医科大学出版社,2013:8-10.
[本文引用:2]
[2] TUNKEL A R,HARTMAN B J,KAPLAN S L,et al.Practice guidelines for the management of bacterial meningitis[J].Clin Infect Dis,2004,39(9):1267-1284.
This article presents guidelines for the treatment of bacterial meningitis. The initial treatment approach to the patient with suspected acute bacterial meningitis depends on early recognition of the meningitis syndrome, rapid diagnostic evaluation, and emergent antimicrobial and adjunctive therapy. Complications associated with lumbar puncture are variable, ranging from mild alterations in comfort to life-threatening brain herniation, which may occur in the patient with elevated intracranial pressure. Several acute-phase reactants have been examined for their usefulness in the diagnosis of acute bacterial meningitis. However, none is diagnostic for bacterial meningitis, and they should not be used to determine whether an individual patient should receive antimicrobial therapy.
DOI:10.1086/425368      PMID:15494903      URL    
[本文引用:2]
[3] WEISFELT M,DE G J,VAN D E A,et al.Community-acquired bacterial meningitis in alcoholic patients[J].PLoS One,2010,5(2):e9102.
Background Alcoholism is associated with susceptibility to infectious disease, particularly bacterial pneumonia. In the present study we described characteristics in alcoholic patients with bacterial meningitis and delineate the differences with findings in non-alcoholic adults with bacterial meningitis. Methods/Principal Findings This was a prospective nationwide observational cohort study including patients aged >16 years who had bacterial meningitis confirmed by culture of cerebrospinal fluid (696 episodes of bacterial meningitis occurring in 671 patients). Alcoholism was present in 27 of 686 recorded episodes of bacterial meningitis (4%) and alcoholics were more often male than non-alcoholics (82% vs 48%, P = 0.001). A higher proportion of alcoholics had underlying pneumonia (41% vs 11% P<0.001). Alcoholics were more likely to have meningitis due to infection with Streptococcus pneumoniae (70% vs 50%, P = 0.01) and Listeria monocytogenes (19% vs 4%, P = 0.005), whereas Neisseria meningitidis was more common in non-alcoholic patients (39% vs 4%, P = 0.01). A large proportion of alcoholics developed complications during clinical course (82% vs 62%, as compared with non-alcoholics; P = 0.04), often cardiorespiratory failure (52% vs 28%, as compared with non-alcoholics; P = 0.01). Alcoholic patients were at risk for unfavourable outcome (67% vs 33%, as compared with non-alcoholics; P<0.001). Conclusions/Significance Alcoholic patients are at high risk for complications resulting in high morbidity and mortality. They are especially at risk for cardiorespiratory failure due to underlying pneumonia, and therefore, aggressive supportive care may be crucial in the treatment of these patients.
DOI:10.1371/journal.pone.0009102      PMID:20161709      URL    
[本文引用:1]
[4] MARTIJN W,DIEDERIK V D B,LODEWI S,et al.Community-acquired bacterial meningitis in older people[J].J Am Geriatr Soc,2006,54(10):1500-1507.
[本文引用:1]
[5] FARBER J M,PETERKIN P I.Listeria monocytogenes,a food-borne pathogen[J].Microbiol Rev,1991,55(4): 752.
ABSTRACT Listeria monocytogenes is a Gram positive, aerobic, facultative anaerobic and nonacid fast bacterium, which can cause the disease listeriosis in both human and animals. It is widely distributed thoroughout the environment and has been isolated from various plant and animal food products associated with listeriosis outbreaks. Contaminated ready-to-eat food products such as gravad and cold-smoked salmon and rainbow trout have been associated with human listeriosis in Sweden. The aim of this study was to analyse the occurrence and level of L. monocytogenes in gravad and cold-smoked salmon (Salmo salar) products packed under vacuum or modified atmosphere from retail outlets in Sweden. Isolated strains were characterized by serotyping and the diversity of the strains within and between producers were determined with PFGE (Pulsed-field gel electrophoresis). The characterized fish isolates were compared with previously characterized human strains. L. monocytogenes was isolated from 11 (three manufacturers) of 56 products analysed. This included gravad salmon products from three manufacturers and cold-smoked salmon from one manufacturer. The highest level of L. monocytogenes found was 1500 cfu/g from a cold-smoked salmon product but the level was low (<100 cfu/g) in most of the products. Serovar 1/2a was predominant, followed by 4b. Three products of gravad salmon harboured more than one serovar. PFGE typing of the 56 salmon isolates detected five Asc I types: four types were identical to human clinical strains with Asc I and one was identical and one was closely related to human clinical strains with Apa I. Isolation of identical or closely related L. monocytogenes strains from human clinical cases of listeriosis and gravad and cold-smoked salmon suggested that these kinds of products are possible sources of listeriosis in Sweden. Therefore, these products should be considered risk products for human listeriosis.
DOI:10.1016/0196-4399(87)90051-1      URL    
[本文引用:1]
[6] MCCOLLUM J T,CRONQUIST A B,SILK B J,et al.Multistate outbreak of listeriosis associated with cantaloupe[J].N Engl J Med,2013,369(10):15791-15800.
Although new pathogen-vehicle combinations are increasingly being identified in produce-related disease outbreaks, fresh produce is a rarely recognized vehicle for listeriosis. We investigated a nationwide listeriosis outbreak that occurred in the United States during 2011.We defined an outbreak-related case as a laboratory-confirmed infection with any of five outbreak-related subtypes of Listeria monocytogenes isolated during the period from August 1 through October 31, 2011. Multistate epidemiologic, trace-back, and environmental investigations were conducted, and outbreak-related cases were compared with sporadic cases reported previously to the Listeria Initiative, an enhanced surveillance system that routinely collects detailed information about U.S. cases of listeriosis.We identified 147 outbreak-related cases in 28 states. The majority of patients (127 of 147, 86%) were 60 years of age or older. Seven infections among pregnant women and newborns and one related miscarriage were reported. Of 145 patients for whom information about hospitalization was available, 143 (99%) were hospitalized. Thirty-three of the 147 patients (22%) died. Patients with outbreak-related illness were significantly more likely to have eaten cantaloupe than were patients 60 years of age or older with sporadic illness (odds ratio, 8.5; 95% confidence interval, 1.3 to 鈭). Cantaloupe and environmental samples collected during the investigation yielded isolates matching all five outbreak-related subtypes, confirming that whole cantaloupe produced by a single Colorado farm was the outbreak source. Unsanitary conditions identified in the processing facility operated by the farm probably resulted in contamination of cantaloupes with L. monocytogenes.Raw produce, including cantaloupe, can serve as a vehicle for listeriosis. This outbreak highlights the importance of preventing produce contamination within farm and processing environments.
DOI:10.1056/NEJMoa1215837      PMID:24004121      URL    
[本文引用:1]
资源
PDF下载数    
RichHTML 浏览数    
摘要点击数    

分享
导出

相关文章:
关键词(key words)
临床药师
脑膜炎
化脓性
李斯特菌


作者
王海涛
仵文英
王娜
刘娜
余静洁