High-dose rifampicin for the treatment of tuberculous meningitis: a meta-analysis of randomized controlled trials.

WHAT IS KNOWN AND OBJECTIVE: Tuberculous meningitis (TBM) is one of the most serious types of extrapulmonary tuberculosis and has caused distress to human. Effective treatment is particularly important. The aim of this meta-analysis is to compare the efficacy of high-dose and standard-dose rifampicin. METHODS: Databases including PubMed, Web of Science, Embase, Scopus and the Cochrane Library databases were electronically searched to identify randomized controlled trials that reported high-dose rifampicin in treatment of patients with TBM. The retrieval time is limited from inception to June 2021. Two reviewers independently screened literature, extracted data and assessed risk bias of included studies. Meta-analysis was performed by using STATA 12.0 software. RESULTS AND DISCUSSION: A total of 12 studies involving 1596 patients were included. The meta-analysis results showed no significant differences in 6-month mortality, 9-month mortality, Grade I-II AE, Grade III-V AE, hepatotoxicity, hepatotoxicity Grade I-II and cardiologic events between high-dose rifampicin (or high-dose rifampicin plus moxifloxacin or levofloxacin) and standard-dose groups. The log(Cmax ) (WMD 0.69, 95%CI 0.59-0.79, p 0.001) and log(AUC0-24h ) (WMD 0.79, 95%CI 0.71-0.88, p 0.001) were higher with high-dose rifampicin. Subgroup analysis revealed the rise of log(Cmax ) in high-dose rifampicin orally was consistent with intravenous administration compared with the control (WMD 0.69, 95%CI 0.66-0.73, p 0.001). WHAT IS NEW AND CONCLUSION: High-dose rifampicin was not a protective factor for 6-month mortality, despite increased plasma Cmax and AUC0-24h . However, the above conclusions are still required to be verified through more RCTs due to the limited quantity of included studies.

Tuberculous meningoencephalitis in a patient with hairy cell leukemia in complete remission.

Tuberculous meningoencephalitis is a rare disease associated with high morbidity and mortality. We report a patient with hairy cell leukemia in complete remission who, after a single cycle of chemotherapy with cladribine, presented fever and neurological deficits. Laboratory diagnosis of tuberculous meningoencephalitis was made by polymerase chain reaction testing for Mycobacterium tuberculosis in cerebrospinal fluid. Despite the prompt institution of antitubercular-therapy, patient's general condition did not improve and he died. Mycobacterial infection should be considered in patients with intra-cranial lesions, affected by hematological malignancies and persistent immunosuppression.

Comparison of conventional bacteriology with nucleic acid amplification (amplified mycobacterium direct test) for diagnosis of tuberculous meningitis before and after inception of antituberculosis chemotherapy.

The role of nucleic acid amplification techniques in the rapid diagnosis of tuberculous meningitis remains uncertain. We compared the performance of Ziehl-Neelsen (ZN) staining, the Gen-Probe amplified Mycobacterium tuberculosis direct test (MTD), and culture with 341 cerebrospinal fluid specimens from 152 adults (73 with and 79 without tuberculous meningitis) before and after inception of antituberculosis chemotherapy. The sensitivity, specificity, and positive and negative predictive values of ZN staining before treatment were 34/66 (52%), 79/79 (100%), 34/34 (100%), and 79/111 (71%), compared with 25/66 (38%), 78/79 (99%), 25/26 (96%), and 79/120 (66%) for MTD. The sensitivity of combined ZN staining and MTD (either positive) was 45/66 (68%). The sensitivity of staining and culture fell more rapidly than that of MTD after the start of treatment: after 5 to 15 days of treatment, MTD was more sensitive than ZN staining (12/43 [28%] versus 2/43 [2%]; P = 0.013). Slower bacterial clearance was observed if M. tuberculosis was resistant to isoniazid and/or streptomycin: resistant organisms were more likely to be cultured from cerebrospinal fluid after 2 to 5 days of treatment than fully sensitive organisms (P < 0.001). The sensitivities of ZN staining, MTD, and the two tests combined were improved by repeated sampling to 38/59 (64%), 35/59 (59%), and 49/59 (83%), respectively. In conclusion, ZN staining of the cerebrospinal fluid is at least as good as MTD for the rapid diagnosis of tuberculosis and is much faster and less expensive. However, the combination of these methods on serial samples detects more cases. Alternative tests are still urgently required.

Breakthrough neurological manifestation during appropriate antituberculous therapy of miliary tuberculosis.

We report a 20-month-old girl with miliary pulmonary tuberculosis and normal neurological findings. While on treatment with isoniazid, rifampicin, pyrazinamide, and ethambutol for 1 month, she developed weakness of the lower extremities without meningism or altered consciousness. A computerized tomogram revealed tuberculomas and basal arachnoiditis. The cerebrospinal fluid findings were compatible with tuberculous meningitis. She responded well to systemic corticosteroids.

Localization of extrapulmonary tuberculosis in the synovial membrane, skin, and meninges in a patient with systemic lupus erythematosus and IgG deficiency.

We report on a 31-year-old female patient with systemic lupus erythematosus (SLE) for 24 years who had a past history of skin tuberculosis (lupus vulgaris), long-term corticosteroid therapy, and IgG deficiency. She presented with monoarthritis and concomitant meningitis from skin tuberculosis after 5 years. The diagnosis of joint and meningeal tuberculosis was defined with clinical symptoms--signs and typical histopathological findings of involved synovium. Clinical improvement was achieved with antituberculous therapy. Cutaneous, articular, and cerebral manifestations of tuberculosis might have been confused with some of the lupus manifestations or lupus activation. It should be kept in mind that tuberculosis may be encountered in SLE due to the nature of the underlying disease and/or its therapy. It is also worth mentioning that, in this patient, tissues involved with extrapulmonary tuberculosis were the primary areas of involvement with SLE.

[Tuberculous meningitis and antibody deficiency disease (author's transl)]. / Tuberkulöse Meningitis und Antikörpermangelsyndrom

A 13 year old girl not vaccinated with BCG became ill with tuberculous meningitis. After administration of 30 g of Streptomycin, cell counts and protein concentrations of the cerebro-spinal fluid returned to normal values. After continuation of antituberculous therapy without Streptomycin, the patient relapsed, and Streptomycin had to be given for 14 months. Defect in humoral immunity was diagnosed with low IgG and low titers of antiviral antibodies. For this reason the patient was additionally treated with passive administration of antibodies.