Senbayrak Seniha, Ozkutuk Nuri, Erdem Hakan, Johansen Isik Somuncu, Civljak Rok, Inal Ayse Seza, Kayabas Uner, Kursun Ebru, Elaldi Nazif, Savic Branislava, Simeon Soline, Yilmaz Emel, Dulovic Olga, Ozturk-Engin Derya, Ceran Nurgul, Lakatos Botond, Sipahi Oguz Resat, Sunbul Mustafa, Yemisen Mucahit, Alabay Selma, Beovic Bojana, Ulu-Kilic Aysegul, Cag Yasemin, Catroux Melanie, Inan Asuman, Dragovac Gorana, Deveci Ozcan, Tekin Recep, Gul Hanefi Cem, Sengoz Gonul, Andre Katell, Harxhi Arjan, Hansmann Yves, Oncu Serkan, Kose Sukran, Oncul Oral, Parlak Emine, Sener Alper, Yilmaz Gulden, Savasci Umit, Vahaboglu Haluk
Department of Infectious Diseases and Clinical Microbiology, Haydarpasa Numune Training and Research Hospital, Istanbul, Turkey.
Department of Medical Microbiology, Celal Bayar University School of Medicine, Manisa, Turkey.
Ann Clin Microbiol Antimicrob. 2015 Nov 4;14:47. doi: 10.1186/s12941-015-0107-z.
Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem. This study aimed to evaluate drug resistance profiles of TBM isolates in adult patients in nine European countries involving 32 centers to provide insight into the empiric treatment of TBM.
Mycobacterium tuberculosis was cultured from the cerebrospinal fluid (CSF) of 142 patients and was tested for susceptibility to first-line antituberculosis drugs, streptomycin (SM), isoniazid (INH), rifampicin (RIF) and ethambutol (EMB).
Twenty of 142 isolates (14.1 %) were resistant to at least one antituberculosis drug, and five (3.5 %) were resistant to at least INH and RIF, [multidrug resistant (MDR)]. The resistance rate was 12, 4.9, 4.2 and 3.5 % for INH, SM, EMB and RIF, respectively. The monoresistance rate was 6.3, 1.4 and 0.7 % for INH, SM and EMB respectively. There was no monoresistance to RIF. The mortality rate was 23.8 % in fully susceptible cases while it was 33.3 % for those exhibiting monoresistance to INH, and 40 % in cases with MDR-TBM. In compared to patients without resistance to any first-line drug, the relative risk of death for INH-monoresistance and MDR-TBM was 1.60 (95 % CI, 0.38-6.82) and 2.14 (95 % CI, 0:34-13:42), respectively.
INH-resistance and MDR rates seemed not to be worrisome in our study. However, considering their adverse effects on treatment, rapid detection of resistance to at least INH and RIF would be most beneficial for designing anti-TB therapy. Still, empiric TBM treatment should be started immediately without waiting the drug susceptibility testing.
由耐抗结核药物的结核分枝杆菌引起的结核性脑膜炎(TBM)是一个日益常见的临床问题。本研究旨在评估欧洲9个国家32个中心成年患者中TBM分离株的耐药谱,以便为TBM的经验性治疗提供依据。
从142例患者的脑脊液(CSF)中培养结核分枝杆菌,并检测其对一线抗结核药物链霉素(SM)、异烟肼(INH)、利福平(RIF)和乙胺丁醇(EMB)的敏感性。
142株分离株中有20株(14.1%)对至少一种抗结核药物耐药,5株(3.5%)对至少INH和RIF耐药,即耐多药(MDR)。INH、SM、EMB和RIF的耐药率分别为12%、4.9%、4.2%和3.5%。INH、SM和EMB的单耐药率分别为6.3%、1.4%和0.7%。对RIF无单耐药情况。完全敏感病例的死亡率为23.8%,对INH单耐药者的死亡率为33.3%,耐多药TBM病例的死亡率为40%。与对任何一线药物均无耐药的患者相比,INH单耐药和耐多药TBM的相对死亡风险分别为1.60(95%CI,0.38 - 6.82)和2.14(95%CI,0.34 - 13.42)。
在我们的研究中,INH耐药率和耐多药率似乎并不令人担忧。然而,考虑到它们对治疗的不利影响,快速检测至少对INH和RIF的耐药性对于设计抗结核治疗最为有益。尽管如此,经验性TBM治疗应立即开始,无需等待药敏试验结果。