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

Analysis of the drug sensitivity test results of the mycobacterium isolates from cerebrospinal fluid of 93 patients with tuberculous meningitis

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χ^2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(χ^2=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)](χ^2=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)](χ^2=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。

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.