93例结核性脑膜炎患者脑脊液分离株耐药性检测结果分析

doi:10.3969/j.issn.1000-6621.2020.11.007

摘要/Abstract

摘要：

目的分析结核性脑膜炎(tuberculous meningitis,TBM)患者脑脊液(cerebrospinal fluid,CSF)分离株耐药性检测结果,为临床治疗结核性脑膜炎药品的选择提供参考。方法收集西安市胸科医院2013年12月至2019年12月CSF培养阳性且菌种鉴定为结核分枝杆菌的93例患者的样本,并进行药物敏感性试验(简称“药敏试验”)。分析对异烟肼(INH)、利福平(RFP)、乙胺丁醇(EMB)、链霉素(Sm)、阿米卡星(Am)、卷曲霉素(Cm)、左氧氟沙星(Lfx)、莫西沙星(Mfx)、丙硫异烟胺(Pto)、对氨基水杨酸钠(PAS)的耐药情况。计数资料采用χ²检验、Fishier精确检验,以P<0.05为差异具有统计学意义。结果 (1)93株分离株中有56株(60.2%)对抗结核药品均敏感,37株(39.8%)对至少一种抗结核药品耐药,19株(20.4%)同时对INH和RFP耐药,即耐多药;(2)总耐药率从高到低分别为INH(31.2%,29/93)>Sm(25.8%,24/93)>RFP(21.5%,20/93)>Lfx(7.5%,7/93)>EMB(5.4%,5/93)=PAS(5.4%,5/93)>Mfx(3.2%,3/93)=Am(3.2%,3/93)=Cm(3.2%,3/93)>Pto(0.0%,0/93);(3)比较初、复治患者对各药品的耐药率,INH耐药率在初复治组[分别为29.3%(22/75)和38.9%(7/18)]差异无统计学意义(χ²=0.618,P=0.432);EMB耐药率在初复治组[分别为4.0%(3/75)和11.1%(2/18)]差异无统计学意义(Fishier精确检验,P=0.247);Am耐药率在初复治组[分别为2.7%(2/75)和5.6%(1/18)]差异无统计学意义(Fishier精确检验,P=0.480);Cm耐药率在初复治组[分别为4.0%(3/75)和0.0%(0/18)]差异无统计学意义(Fishier精确检验,P=1.000);Mfx耐药率在初复治组[分别为1.3%(1/75)和11.1%(2/18)]差异无统计学意义(采用Fishier精确检验,P=0.095);RFP耐药率在初治组[17.3%(13/75)]低于复治组[38.9%(7/18)](χ²=3.996,P=0.046);Sm耐药率在初治组[20.0%(15/75)]低于复治组[50.0%(9/18)](χ²=6.823,P=0.009);Lfx耐药率在初治组[2.7%(2/75)]低于复治组[27.8%(5/18)](Fishier精确检验,P=0.003)。结论 TBM患者CSF结核分枝杆菌临床分离株对一线抗结核药品INH、Sm、RFP的耐药现象较为严重,二线抗结核药品中对Lfx耐药情况最为严重,对Am、Cm、Pto敏感性较好。在TBM治疗中应考虑到初、复治患者耐药情况的不同,合理制定化疗方案,以改善患者预后。

关键词: 结核,脑膜, 微生物敏感性试验, 结核,抗多种药物性, 数据说明,统计

Abstract:

Objective To analyze the drug resistance of mycobacteria isolated from the cerebrospinal fluid (CSF) in patients with tuberculous meningitis (TBM), to provide reference for the clinical management of TBM. Methods A total of 93 samples from 93 patients with positive CSF culture and bacterial strains identified as Mycobacterium tuberculosis were collected from December 2013 to December 2019 in Xi’an Chest Hospital, and a drug sensitivity test was conducted. Drug-resistance rates to isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), amikacin (Am), capreomycin (Cm), levofloxacin (Lfx), moxifloxacin (Mfx), prothionamide (Pto), and para-aminosalicylic acid (PAS) were collected and analyzed. The data was tested using chi-square test and Fisher’s exact test, and P<0.05 was considered statistically significant. Results (1) Of the 93 isolates, 56 (60.2%) were sensitive to all the anti-TB drugs, 37 (39.8%) were resistant to at least one anti-TB drug, and 19 (20.4%) were resistant to both INH and RFP (i.e. multidrug resistant, MDR).(2) The drug-resistance rates from high to low were INH(31.2%, 29/93)>Sm(25.8%, 24/93)>RFP(21.5%, 20/93)>Lfx(7.5%, 7/93)>EMB(5.4%, 5/93)=PAS(5.4%, 5/93)>Mfx(3.2%, 3/93)=Am(3.2%, 3/93)=Cm(3.2%, 3/93)>Pto(0.0%, 0/93). (3) Comparing the drug resistance rates of the newly-treated and retreated patients with tuberculosis showed that the drug-resistance rates to INH in the newly-treated group and retreated group(29.3% (22/75) and 38.9% (7/18) respectively)were not statistically different (χ ²=0.618, P=0.432); the drug-resistance rates to EMB in the newly-treated group and retreated group (4.0% (3/75) and 11.1% (2/18), respectively) were not statistically different (Fischer’s exact test, P=0.247); the drug resistance rates to Am in the newly-treated group and retreated group (2.7% (2/75) and 5.6% (1/18) respectively) were not statistically different (Fischer’s exact test, P=0.480); the drug resistance rates to Cm in the newly-treated group and retreated group (4.0% (3/75) and 0.0% (0/18) respectively) were not statistically different (Fischer’s exact test, P=1.000); the drug-resistance rates to Am in the newly-treated group and retreated group(respectively were 1.3% (1/75) and 11.1% (2/18)) were not statistically different (Fischer’s exact test, P=0.095); the drug resistance rate to RFP in the newly-treated group (17.3% (13/75)) was statistically lower than the retreated group (38.9% (7/18)) (χ ²=3.996, P=0.046); the drug resistance rate to Sm in the newly-treated group (20.0% (15/75)) was statistically significant lower than the retreated group (50.0% (9/18)) (χ ²=6.823, P=0.009); the drug resistance rate of Lfx in the newly-treated group (2.7% (2/75)) was statistically significant lower than the retreated group (27.8% (5/18))(Fischer’s exact test, P=0.003). Conclusion The clinical isolates of Mycobacterium tuberculosis from CSF of the TBM patients are more resistant to the first-line anti-tuberculosis drugs: INH, Sm and RFP. Among the second-line anti-tuberculosis drugs, the resistance to Lfx is the most serious, and the sensitivity to Am, Cm and Pto is better. In the treatment of TBM, the difference in drug resistance between the newly-treated and retreated patients should be considered, and a reasonable chemotherapy regimen should be formulated to improve the patient’s prognosis.

Key words: Tuberculosis,meninges, Microbial sensitivity test, Tuberculosis,multi-drug resistant, Data interpretation,statistical

冯莹, 马进宝, 杨翰, 杨元利, 任斐. 93例结核性脑膜炎患者脑脊液分离株耐药性检测结果分析[J]. 中国防痨杂志, 2020, 42(11): 1177-1182. doi: 10.3969/j.issn.1000-6621.2020.11.007

FENG Ying, MA Jin-bao, YANG Han, YANG Yunan-li, REN Fei. Analysis of the drug sensitivity test results of the mycobacterium isolates from cerebrospinal fluid of 93 patients with tuberculous meningitis[J]. Chinese Journal of Antituberculosis, 2020, 42(11): 1177-1182. doi: 10.3969/j.issn.1000-6621.2020.11.007

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耐药种类	耐药例 (株)数	耐药率 (%)
INH+RFP	2	10.5
INH+RFP+EMB	0	0.0
INH+RFP+Sm	9	47.4
INH+RFP+EMB+Sm	2	10.5
INH+RFP+Sm+FQs	3	15.8
INH+RFP+Sm+Am/Cm	1	5.3
INH+RFP+EMB+ FQs	0	0.0
INH+RFP+EMB+Am/Cm	0	0.0
INH+RFP+EMB+Sm+ FQs	1	5.3
INH+RFP+EMB+Sm+Am/Cm	1	5.3
INH+RFP+EMB+Sm+FQs+Am/Cm	0	0.0
合计	19	100.0