Clinical study of dynamic changes of cerebrospinal fluid cytology in drug resistant tuberculous meningitis

Abstract

Objective To summarize the dynamic changes of cerebrospinal fluid (CSF) cytology in drug resistant tuberculous meningitis (TBM), and to explore its value in drug resistance and efficacy evaluation of TBM. Methods Seventy⁃nine patients with TBM who were diagnosed and treated in Jiangxi Chest Hospital from January 2013 to December 2020 were included in this study. H(S)REZ(V) scheme [isoniazid (or streptomycin), rifampicin, ethambutol, plus pyrazinamide (or levofloxacin)] regimen was adopted before the return of drug sensitivity test results. After the return of results, individualized anti⁃tuberculosis regimen was formulated according to drug resistance. Results According to the drug sensitivity test results of CSF, 37 cases were drug resistant TBM, of which 29 cases (78.38%) were multidrug resistant. The drug resistance spectrum was isoniazid + rifampicin + streptomycin [35.14% (13/37)], isoniazid + rifampicin + streptomycin + fluoroquinolone [18.92% (7/37)], isoniazid + rifampicin + ethambutol + streptomycin [16.22% (6/37)], isoniazid and rifampicin [10.81% each, (4/37)], Isoniazid + rifampicin, isoniazid + rifampicin + ethambutol + streptomycin + fluoroquinolone, isoniazid + rifampicin + ethambutol + streptomycin + amikacin/capreomycin [2.70% each, (1/37)]. After 2 and 4 weeks of antituberculosis treatment, the number of nucleated cells in CSF of non drug resistant group (t=5.050, P=0.000; t=11.100, P=0.000) and neutrophil ratio (t=15.268, P=0.000; t=17.048, P=0.000) were lower than drug resistant group. CSF cytology showed that the drug resistant group showed mixed cell inflammatory reaction lasting more than 4 weeks, and the non drug resistant group transformed into significant lymphocyte reaction. After 6 months of follow⁃up, the total effective rate of drug resistant group was lower than that of non drug resistant group [45.71% (16/35) vs. 90% (36/40); χ2=17.218, P=0.000]. Conclusions The cytological characteristics of CSF in patients with TBM are mainly characterized by mixed cell inflammatory reaction in the early stage, the delayed mixed cell inflammatory reaction lasting more than 4 weeks during treatment is the characteristic of drug resistant TBM, which may be the basis for indicating that the treatment plan is invalid. When limited by the time limit and conditions of drug sensitivity test, monitoring the dynamic changes of CSF cytology may become an auxiliary judgment method for drug resistant TBM, which can provide reference for clinical efficacy evaluation and antituberculosis treatment plan adjustment.

Keywords

• tuberculosis meningeal
• drug tolerance
• microbial sensitivity tests
• cerebrospinal fluid
• cytological techniques