Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study

Seniha Senbayrak, Nuri Ozkutuk, Hakan Erdem, Isik Somuncu Johansen, Rok Civljak, Ayse Seza Inal, Uner Kayabas, Ebru Kursun, Nazif Elaldi, Branislava Savic, Soline Simeon, Emel Yilmaz, Olga Dulovic, Derya Ozturk-Engin, Nurgul Ceran, Botond Lakatos, Oguz Resat Sipahi, Mustafa Sunbul, Mucahit Yemisen, Selma Alabay, Bojana Beovic, Aysegul Ulu-Kilic, Yasemin Cag, Melanie Catroux, Asuman Inan, Gorana Dragovac, Ozcan Deveci, Recep Tekin, Hanefi Cem Gul, Gonul Sengoz, Katell Andre, Arjan Harxhi, Yves Hansmann, Serkan Oncu, Sukran Kose, Oral Oncul, Emine Parlak, Alper Sener, Gulden Yilmaz, Umit Savasci, Haluk Vahaboglu

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.