Six months therapy for tuberculous meningitis

Abstract

BackgroundTuberculous meningitis (TBM) is the main form of tuberculosis that affects the central nervous system and is associated with high rates of death and disability. Most international guidelines recommend longer antituberculous treatment (ATT) regimens for TBM than for pulmonary tuberculosis disease to prevent relapse. However, longer regimens are associated with poor adherence, which could contribute to increased relapse, development of drug resistance, and increased costs to patients and healthcare systems.ObjectivesTo compare the effects of short-course (six months) regimens versus prolonged-course regimens for people with tuberculous meningitis (TBM).Search methodsWe searched the following databases up to 31 March 2016: the Cochrane Infectious Diseases Group Specialized Register; the Cochrane Central Register of Controlled Trials (CENTRAL), published in the Cochrane Library; MEDLINE; EMBASE; LILACS; INDMED; and the South Asian Database of Controlled Clinical Trials. We searched the World Health Organization International Clinical Trials Registry Platform (WHO ICTRP) and ClinicalTrials.gov for ongoing trials. We also checked article reference lists and contacted researchers in the field.Selection criteriaWe included randomized controlled trials (RCTs) and prospective cohort studies of adults and children with TBM treated with antituberculous regimens that included rifampicin for six months or longer than six months. The primary outcome was relapse, and included studies required a minimum of six months follow-up after completion of treatment.Data collection and analysisTwo review authors (SJ and HR) independently assessed the literature search results for eligibility, and performed data extraction and 'Risk of bias' assessments of the included studies. We contacted study authors for additional information when necessary. Most data came from single arm cohort studies without a direct comparison so we pooled the findings for each group of cohorts and presented them separately using a complete-case analysis. We assessed the quality of the evidence narratively, as using the Grading of Recommendations Assessment, Development and Evaluation (GRADE) approach was inappropriate with no direct comparisons between short- and prolonged-course regimens.Main resultsFour RCTs and 12 prospective cohort studies met our inclusion criteria, and included a total of 1881 participants with TBM. None of the included RCTs directly compared six months versus longer regimens, so we analysed all data as individual cohorts to obtain relapse rates in each set of cohorts.We included seven cohorts of participants treated for six months, with a total of 458 participants. Three studies were conducted in Thailand, two in South Africa, and one each in Ecuador and Papua New Guinea between the 1980s and 2009. We included 12 cohorts of participants treated for longer than six months (ranging from eight to 16 months), with a total of 1423 participants. Four studies were conducted in India, three in Thailand and one each in China, South Africa,...

Prevailing practices in the treatment of tuberculous meningitis (TBM): a cross-sectional study

“…Although the evidence on the duration of treatment for TBM advocates 6 months,6 the reality is quite contrary. The reasons for this mismatch may be lack of good quality of evidence, non-pragmatic trial designs and tendency to treat sicker patients aggressively since they are usually excluded from trials.…”

“…Although there are no trials comparing duration of intensive phase in patients with TBM, there are more than 20 different treatment regimens published for treatment of TBM 6. These are based on institutional or individual treating practices.…”

Clinical Features and Outcome in Adult Cases of Tuberculous Meningitis in Tertiary Care Hospital in Antananarivo, Madagascar

“…However, most of international guidelines including current WHO guideline recommend longer course of treatment ranging from 9 to 12 months [29–31]. Furthermore, short-term therapy is not supported by strong evidence [32]. However, neither the length nor the optimal treatment regimen is well known in TBM.…”

Treatment of Central Nervous System Tuberculosis

“…6,35 In contrast, no randomized controlled trials have established the optimal duration of treatment of TBM or CNS-TB. Although multiple reports of 6-month treatment of TBM in both adults and children have been published, 36 guidelines continue to recommend a 2-month intensive phase followed by 7-to 10-month continuation phase (►Table 4). Two main concerns have led to the perception that treatment for longer than 6 months is needed for TBM to ensure cure and prevent relapse: (1) the blood-brain barrier hinders penetration of antituberculosis drugs to reach adequate drug concentrations at the infected site and therefore it may take longer to eradicate bacilli within the CNS and (2) the monitoring for response to treatment is not as reliable as with PTB, in which sputum microscopy and culture can be used.…”

“…Publications as early as 1956 provide anecdotal evidence of the effectiveness of 6-month regimens for the treatment of TBM in children. [36][37][38] Recent studies prospectively evaluating short-course treatment regimens in children are detailed in ►Table 6. In a comparison of 12-, 9-, and 6-month courses used during various time periods in Thai children with TBM, the 6-month regimen, intensified with pyrazinamide in the initial phase, was significantly more efficacious in preventing total negative outcomes.…”