Tuberculous Meningitis

A comprehensive, evidence-based clinical reference app for the diagnosis and management of tuberculous meningitis Based on the TBMRC 2019 consensus diagnostic criteria (Lancet Infectious Diseases), NICE NG33 tuberculosis guidelines, WHO 2017 treatment guidelines, and landmark clinical trials including Thwaites et al. NEJM 2004 (dexamethasone) and Torok et al. 2011 (ART timing in HIV/TBM). KEY SECTIONS: Clinical features: subacute onset, cranial nerve palsies, seizures, papilloedema, TB prodrome CSF INTERPRETATION -- CSF profile comparison table: TBM vs bacterial vs viral vs cryptococcal meningitis pattern TREATMENT PROTOCOL (4 tabs) -- Standard HRZE regimen: intensive phase 2 months then continuation phase 7-10 months -- Adult weight-based dosing: isoniazid (5 mg/kg), rifampicin (10-15 mg/kg), pyrazinamide (25-30 mg/kg), ethambutol (15-20 mg/kg), pyridoxine (mandatory co-prescription) -- Fluoroquinolone substitution for ethambutol: levofloxacin 1000 mg OD or moxifloxacin 400 mg OD (better CNS penetration than EMB) -- Ruslami 2013 and Heemskerk 2016 evidence -- High-dose rifampicin: 15-20 mg/kg/day intensified protocol -- Paediatric dosing: WHO weight-based doses -- Special situations: pregnancy (PZA now recommended), renal impairment, hepatic impairment with bridge regimen COMPLICATIONS -- Hydrocephalus: communicating (75-85% of TBM) vs non-communicating; neurosurgical criteria; EVD and VP shunting -- Raised ICP management: mannitol 0.25-1 g/kg, hypertonic saline, head positioning -- TBM vasculitis and stroke: perforating artery territory infarction, MRI DWI, management -- TBM-IRIS (paradoxical reaction): recognition, increased dexamethasone, do not stop antituberculosis therapy -- Seizure management: levetiracetam preferred; avoid phenytoin and carbamazepine (rifampicin interaction) -- Hyponatraemia: SIADH vs cerebral salt wasting differentiation and management HIV CO-INFECTION -- ART timing: defer 4-8 weeks (critical difference from pulmonary TB) -- Torok 2011 trial -- ART regimen: efavirenz preferred with rifampicin; dolutegravir 50 mg TWICE daily (dose adjustment) -- Contraindicated with rifampicin: all protease inhibitors, nevirapine, rilpivirine -- Cryptococcal screen mandatory: serum and CSF CrAg in all HIV-positive patients -- PCP prophylaxis: co-trimoxazole if CD4 below 200 DRUG RESISTANCE -- MDR/Pre-XDR/XDR-TB 2021 WHO definitions -- CNS penetration of second-line drugs: linezolid and fluoroquinolones (good) vs bedaquiline and clofazimine (poor) -- Suggested MDR-TBM regimen: levofloxacin + linezolid + cycloserine + pyrazinamide + ethionamide MONITORING AND FOLLOW-UP -- Full monitoring table: LFTs, FBC, renal function, uric acid, visual acuity, glucose -- DILI protocol: when to stop hepatotoxic drugs, bridge regimen, rechallenge order -- Repeat CSF and neuroimaging schedule -- Clinic follow-up timeline: 2 weeks, 6 weeks, 2 months, 3-monthly, end of treatment -- Contact tracing and PHE notification guidance REFERENCES (20+ citations) -- TBMRC Consensus Statement (Lancet Infectious Diseases 2019) -- NICE NG33 Tuberculosis guidelines (2016, updated 2019) -- WHO Guidelines for Treatment of Drug-Susceptible Tuberculosis (2017) -- Thwaites GE et al. NEJM 2004 (dexamethasone) -- Torok ME et al. CID 2011 (ART timing in HIV/TBM) -- Ruslami R et al. Lancet ID 2013 (intensified regimen) -- Heemskerk AD et al. NEJM 2016 (high-dose rifampicin) -- Bahr NC et al. Lancet ID 2014 (Xpert in TBM) -- And 12+ additional peer-reviewed publications FOR HEALTHCARE PROFESSIONALS ONLY This app is an educational reference tool for qualified healthcare professionals. It does not replace clinical assessment, specialist review, or local tuberculosis service guidance. All prescribing decisions should be made with appropriate specialist input.