Abstract:

Objective To analyze the drug resistance of mycobacteria isolated from the cerebrospinal fluid (CSF) in patients with tuberculous meningitis (TBM), to provide reference for the clinical management of TBM. Methods A total of 93 samples from 93 patients with positive CSF culture and bacterial strains identified as Mycobacterium tuberculosis were collected from December 2013 to December 2019 in Xi’an Chest Hospital, and a drug sensitivity test was conducted. Drug-resistance rates to isoniazid (INH), rifampicin (RFP), ethambutol (EMB), streptomycin (Sm), amikacin (Am), capreomycin (Cm), levofloxacin (Lfx), moxifloxacin (Mfx), prothionamide (Pto), and para-aminosalicylic acid (PAS) were collected and analyzed. The data was tested using chi-square test and Fisher’s exact test, and P<0.05 was considered statistically significant. Results (1) Of the 93 isolates, 56 (60.2%) were sensitive to all the anti-TB drugs, 37 (39.8%) were resistant to at least one anti-TB drug, and 19 (20.4%) were resistant to both INH and RFP (i.e. multidrug resistant, MDR).(2) The drug-resistance rates from high to low were INH(31.2%, 29/93)>Sm(25.8%, 24/93)>RFP(21.5%, 20/93)>Lfx(7.5%, 7/93)>EMB(5.4%, 5/93)=PAS(5.4%, 5/93)>Mfx(3.2%, 3/93)=Am(3.2%, 3/93)=Cm(3.2%, 3/93)>Pto(0.0%, 0/93). (3) Comparing the drug resistance rates of the newly-treated and retreated patients with tuberculosis showed that the drug-resistance rates to INH in the newly-treated group and retreated group(29.3% (22/75) and 38.9% (7/18) respectively)were not statistically different (χ ²=0.618, P=0.432); the drug-resistance rates to EMB in the newly-treated group and retreated group (4.0% (3/75) and 11.1% (2/18), respectively) were not statistically different (Fischer’s exact test, P=0.247); the drug resistance rates to Am in the newly-treated group and retreated group (2.7% (2/75) and 5.6% (1/18) respectively) were not statistically different (Fischer’s exact test, P=0.480); the drug resistance rates to Cm in the newly-treated group and retreated group (4.0% (3/75) and 0.0% (0/18) respectively) were not statistically different (Fischer’s exact test, P=1.000); the drug-resistance rates to Am in the newly-treated group and retreated group(respectively were 1.3% (1/75) and 11.1% (2/18)) were not statistically different (Fischer’s exact test, P=0.095); the drug resistance rate to RFP in the newly-treated group (17.3% (13/75)) was statistically lower than the retreated group (38.9% (7/18)) (χ ²=3.996, P=0.046); the drug resistance rate to Sm in the newly-treated group (20.0% (15/75)) was statistically significant lower than the retreated group (50.0% (9/18)) (χ ²=6.823, P=0.009); the drug resistance rate of Lfx in the newly-treated group (2.7% (2/75)) was statistically significant lower than the retreated group (27.8% (5/18))(Fischer’s exact test, P=0.003). Conclusion The clinical isolates of Mycobacterium tuberculosis from CSF of the TBM patients are more resistant to the first-line anti-tuberculosis drugs: INH, Sm and RFP. Among the second-line anti-tuberculosis drugs, the resistance to Lfx is the most serious, and the sensitivity to Am, Cm and Pto is better. In the treatment of TBM, the difference in drug resistance between the newly-treated and retreated patients should be considered, and a reasonable chemotherapy regimen should be formulated to improve the patient’s prognosis.

Key words: Tuberculosis,meninges, Microbial sensitivity test, Tuberculosis,multi-drug resistant, Data interpretation,statistical