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[中性粒细胞减少和非中性粒细胞减少的抗生素相关性腹泻患者中艰难梭菌毒素的频率及危险因素分析]

[The frequency of Clostridium difficile toxin in neutropenic and non-neutropenic patients with antibiotic-associated diarrhea and analysis of the risk factors].

作者信息

Tunçcan Ozlem Güzel, Ulutan Fatma, Karakuş Resul

机构信息

Gazi Universitesi Tip Fakültesi, Enfeksiyon Hastaliklari ve Klinik Bakteriyoloji Anabilim Dali, Ankara.

出版信息

Mikrobiyol Bul. 2008 Oct;42(4):573-83.

Abstract

This study was carried out in order to investigate the frequency of Clostridium difficile toxin in the stool samples of hospitalized 74 neutropenic (mean age: 41.78 +/- 14.3 years; 40 male) and 75 non-neutropenic patients (mean age: 44.09 +/- 15.6 years; 30 male) who developed antibiotic-associated diarrhea between January 2003-September 2004 in a university hospital and also to analyze the related risk factors. C. difficile toxin A and toxin A/B were searched by immunochromatographic method (Toxin Detection Kit, Oxoid, UK), and commercial ELISA (Clostridium difficile Antigen, Generic Assays GmbH, Germany) kit, respectively. Stool samples were also analysed in terms of the presence of other bacterial and parasitic agents which may cause diarrhea. Statistical evaluation were performed by Kaplan-Meier survival analysis and by Cox regression analysis. Both neutropenic and non-neutropenic groups were compared according to their incidence densities based on times in days of overall hospitalization, total antibiotic use and hospitalization until diagnosis. The antibiotics used in neutropenic patients were piperacillin-tazobactam (41.9%), imipenem (25.7%), cefepime (17.5%), ciprofloxacin (2.7%) and others (12.2%) and in non-neutropenic patients were ampicillin-sulbactam (29.3%), ciprofloxacin (18.7%), ceftriaxone (14.6%) and others (30.7%). C. difficile toxin A positivity rates in neutropenic and non-neutropenic groups were found as 13.5% (10/74) and 14.7% (11/75), respectively, with a total rate of 14.1% (21/149). The positivity rate of toxin A/B was 24.3% (n= 18) for neutropenic, and 21.3% (n= 16) for non-neutropenic patients, with a total rate of 22.8% (n= 34). There was no statistically significant difference between the groups by means of toxin A or toxin A/B positivity rates (p > 0.05). Thirteen (38.2%) of 34 toxin A/B positive patients yielded negative results with toxin A detection test. Our results revealed that infection in the neutropenic patients developed much earlier than that in the non-neutropenic group by comparing durations of hospitalization and antibotic use which were shorter for toxin positive individuals (p < 0.01 and p < 0.001, respectively). In the control group, implementation of sulbactam-ampicillin or amoxicillin-clavulanate was determined as a risk factor. In addition to duration of hospitalization, use of antibiotics was evaluated as a risk factor for C. difficile associated colitis, especially in the neutropenic group. According to these results, it is possible to point out that antibiotic-associated colitis develops relatively earlier in neutropenic patients and is more frequently C. difficile toxin positive. In this context, appropriate control measures should therefore be kept in mind.

摘要

本研究旨在调查2003年1月至2004年9月期间在某大学医院发生抗生素相关性腹泻的74例中性粒细胞减少患者(平均年龄:41.78±14.3岁;40例男性)和75例非中性粒细胞减少患者(平均年龄:44.09±15.6岁;30例男性)粪便样本中艰难梭菌毒素的频率,并分析相关危险因素。分别采用免疫层析法(毒素检测试剂盒,Oxoid,英国)和商业ELISA法(艰难梭菌抗原,通用检测有限公司,德国)检测艰难梭菌毒素A和毒素A/B。还对粪便样本中可能导致腹泻的其他细菌和寄生虫进行了分析。采用Kaplan-Meier生存分析和Cox回归分析进行统计学评估。根据中性粒细胞减少组和非中性粒细胞减少组在总住院天数、总抗生素使用天数和诊断前住院天数的发病密度进行比较。中性粒细胞减少患者使用的抗生素为哌拉西林-他唑巴坦(41.9%)、亚胺培南(25.7%)、头孢吡肟(17.5%)、环丙沙星(2.7%)和其他(12.2%),非中性粒细胞减少患者使用的抗生素为氨苄西林-舒巴坦(29.3%)、环丙沙星(18.7%)、头孢曲松(14.6%)和其他(30.7%)。中性粒细胞减少组和非中性粒细胞减少组艰难梭菌毒素A阳性率分别为13.5%(10/74)和14.7%(11/75),总阳性率为14.1%(21/149)。毒素A/B阳性率在中性粒细胞减少患者中为24.3%(n = 18),在非中性粒细胞减少患者中为21.3%(n = 16),总阳性率为22.8%(n = 34)。两组间毒素A或毒素A/B阳性率无统计学显著差异(p>0.05)。34例毒素A/B阳性患者中有13例(38.2%)毒素A检测试验结果为阴性。通过比较毒素阳性个体住院时间和抗生素使用时间较短(分别为p<0.01和p<0.001),我们的结果显示中性粒细胞减少患者的感染比非中性粒细胞减少组发生得更早。在对照组中,确定使用舒巴坦-氨苄西林或阿莫西林-克拉维酸为危险因素。除住院时间外,抗生素的使用被评估为艰难梭菌相关性结肠炎的危险因素,尤其是在中性粒细胞减少组。根据这些结果,可以指出抗生素相关性结肠炎在中性粒细胞减少患者中发病相对较早,且更频繁地为艰难梭菌毒素阳性。因此,应牢记适当的控制措施。

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