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

Seniha Şenbayrak ,Recep Tekin,Emine Parlak,Selma Alabay,Botond Lakatos,Arjan Harxhi,Yves Hansmann,Hakan Erdem,Gorana Dragovac,Emel Yılmaz ,Branislava Savić ,Oral Öncül ,Alper Şener ,Ümit Savaşçı ,Gülden Yılmaz ,S Siméon ,O Dulović ,Gönül Şengöz ,Yasemin Çağ ,Hanefi Cem Gül ,Üner Kayabaş ,Rok Čivljak ,Özcan Deveci ,Mustafa Sünbül ,Şükran Köse ,Serkan Öncü ,Oğuz Reşat Sıpahi ,Mücahit Yemişen ,Derya Öztürk-Engin ,Asuman İnan ,Ayşe Seza İnal ,Işik Somuncu Johansen ,Nuri Özkütük ,Ebru Kurşun ,Nurgül Ceran ,Bojana Beović ,Keila Magalhães André ,Nazif Elaldı ,M Catroux ,Ayşegül Ulu-Kılıç ,Haluk Vahaboğlu

doi:10.1186/s12941-015-0107-z

Abstract

BackgroundTuberculous 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.MethodsMycobacterium 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).ResultsTwenty 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.ConclusionINH-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.

Highlights

Tuberculous meningitis (TBM) caused by Mycobacterium tuberculosis resistant to antituberculosis drugs is an increasingly common clinical problem
In accordance with increasing drug resistance seen in TB cases worldwide, the number of drug-resistant TBM cases has been on the incline, making drug-resistant TBM a more challenging clinical problem [2, 8, 11]
Given that the isolates tested in our study were obtained basically from European countries, it can be expected that the rate of susceptibility to all the four first-line drugs in our TBM cases would likely to be similar to that reported for all TB cases

Summary

Introduction

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. World health organization (WHO) estimated that 9 million people developed TB and 1.5 million people died of this disease in 2013. The same report emphasized the development of multidrug resistant tuberculosis [MDR-TB, defined as resistance to at least isoniazid (INH) and rifampicin (RIF)] in an estimated 480,000 people in 2013, of which only half of them could be diagnosed [1]. Tuberculous meningitis (TBM) is a very serious form of extrapulmonary TB, accounting for 5–10 % and requiring prompt treatment [2]. One of the most important factors affecting the prognosis is early diagnosis and proper treatment [3]

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