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    Antituberculosis drug resistance patterns in adults with tuberculous meningitis: results of haydarpasa-iv study
    (Biomed Central Ltd, 2015) Senbayrak, Seniha; Ozkutuk, Nuri; Erdem, Hakan; Johansen, Isik Somuncu; Civljak, Rok; Inal, Ayse Seza; Kayabas, Uner
    Background: 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. Methods: 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). Results: 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 firstline 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. Conclusion: 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.
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    Central nervous system infections in the absence of cerebrospinal fluid pleocytosis
    (Elsevier B.V., 2017) Erdem, Hakan; Ozturk-Engin, Derya; Cag, Yasemin; Senbayrak, Seniha; Inan, Asuman; Kazak, Esra; Savasci, Umit
    Previous multicenter/multinational studies were evaluated to determine the frequency of the absence of cerebrospinal fluid pleocytosis in patients with central nervous system infections, as well as the clinical impact of this condition. It was found that 18% of neurosyphilis, 7.9% of herpetic meningoencephalitis, 3% of tuberculous meningitis, 1.7% of Brucella meningitis, and 0.2% of pneumococcal meningitis cases did not display cerebrospinal fluid pleocytosis. Most patients were not immunosuppressed. Patients without pleocytosis had a high rate of unfavorable outcomes and thus this condition should not be underestimated. © 2017 The Author(s)
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    The diagnostic utility of the Thwaites' system and lancet consensus scoring system in tuberculous vs. non-tuberculous subacute and chronic meningitis: multicenter analysis of 395 adult patients
    (BMC, 2020) Sulaiman, Tarek; Medi, Sai; Erdem, Hakan; Senbayrak, Seniha; Ozturk-Engin, Derya; Inan, Asuman; Civljak, Rok
    Background Tuberculous meningitis (TBM) represents a diagnostic and management challenge to clinicians. The Thwaites' system and Lancet consensus scoring system are utilized to differentiate TBM from bacterial meningitis but their utility in subacute and chronic meningitis where TBM is an important consideration is unknown. Methods A multicenter retrospective study of adults with subacute and chronic meningitis, defined by symptoms greater than 5 days and less than 30 days for subacute meningitis (SAM) and greater than 30 days for chronic meningitis (CM). The Thwaites' system and Lancet consensus scoring system scores and the diagnostic accuracy by sensitivity, specificity, and area under the curve of receiver operating curve (AUC-ROC) were calculated. The Thwaites' system and Lancet consensus scoring system suggest a high probability of TBM with scores <= 4, and with scores of >= 12, respectively. Results A total of 395 patients were identified; 313 (79.2%) had subacute and 82 (20.8%) with chronic meningitis. Patients with chronic meningitis were more likely caused by tuberculosis and had higher rates of HIV infection (P < 0.001). A total of 162 patients with TBM and 233 patients with non-TBM had unknown (140, 60.1%), fungal (41, 17.6%), viral (29, 12.4%), miscellaneous (16, 6.7%), and bacterial (7, 3.0%) etiologies. TMB patients were older and presented with lower Glasgow coma scores, lower CSF glucose and higher CSF protein (P < 0.001). Both criteria were able to distinguish TBM from bacterial meningitis; only the Lancet score was able to differentiate TBM from fungal, viral, and unknown etiologies even though significant overlap occurred between the etiologies (P < .001). Both criteria showed poor diagnostic accuracy to distinguish TBM from non-TBM etiologies (AUC-ROC was <. 5), but Lancet consensus scoring system was fair in diagnosing TBM (AUC-ROC was .738), sensitivity of 50%, and specificity of 89.3%. Conclusion Both criteria can be helpful in distinguishing TBM from bacterial meningitis, but only the Lancet consensus scoring system can help differentiate TBM from meningitis caused by fungal, viral and unknown etiologies even though significant overlap occurs and the overall diagnostic accuracy of both criteria were either poor or fair.