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Comparative Efficacy of Adjuvant Rifampicin, Levofloxacin, and Their Combination in Tuberculous Meningitis with and Without HIV Co-Infection: A Systematic Review and Meta-Analysis

24 Pages Posted: 16 Jan 2025

See all articles by Nathania Nathania

Nathania Nathania

Airlangga University - Faculty of Medicine

Kiran T. Thakur

Department of Neurology - Columbia University Irving Medical Center

Fransiskus Xaverius Rinaldi

Ende Regional General Hospital

Maulana Empitu

Airlangga University - Faculty of Medicine

Stevan Kristian Lionardi

Fatima Hospital

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Abstract

Objective: This study evaluates the efficacy of increased-dose rifampicin, additional levofloxacin, and their combination in treating tuberculous meningitis (TBM) with and without human immunodeficiency virus (HIV) co-infection.

Background: TBM remains a significant clinical challenge, particularly in regions with high tuberculosis (TB) and HIV prevalence, where mortality and morbidity rates persist despite advances in treatment. The interplay between TBM and HIV therapies could lead to potential drug interactions, underscoring the urgent need to systematically assess the effectiveness of adjunctive rifampicin, levofloxacin, and their combination.

Design/Methods: This review analyzed data from nine databases (Scopus, PubMed, Cochrane, Sage Pub, ProQuest, PLOS, EBSCO, Epistemonikos, and Springer) using predefined keywords. The focus was on TBM with and without HIV, comparing the efficacy of increased-dose rifampicin, additional levofloxacin, and their combination against standard therapy. Quality assessment was conducted using the Risk of Bias version 2 (RoB v2) tool. A meta-analysis was performed using Review Manager 5.4.Results: Six studies, including 1,337 participants, were analyzed. The assessment of mortality rates showed non-significant results, with pooled hazard ratios 0.85 (95% CI; 0.66, 1.10; P = 0.21) for additional levofloxacin and 0.65 (95% CI, 0.30 to 1.39; P=0.27) for increased-dose rifampicin, compared to standard therapy. Furthermore, there was no significant correlation within additional levofloxacin and neurologic adverse events, or increased-dose rifampicin and serious adverse events 

Conclusion: While increased-dose rifampicin and additional levofloxacin showed trends toward improved survival in specific subgroups, the lack of significant overall benefits and the associated risks of adverse events suggest that these interventions may not be universally recommended as adjunctive therapies for TBM. Further research targeting specific patient populations, such as those with severe disease or HIV co-infection, is necessary to define their role in clinical practice.

Keywords: Tuberculous Meningitis, Rifampicin, Levofloxacin, HIV Co-infection, Infectious Disease, Neuroinfectious Disease, Meta Analysis

Suggested Citation

Nathania, Nathania and Thakur, Kiran T. and Rinaldi, Fransiskus Xaverius and Empitu, Maulana and Lionardi, Stevan Kristian, Comparative Efficacy of Adjuvant Rifampicin, Levofloxacin, and Their Combination in Tuberculous Meningitis with and Without HIV Co-Infection: A Systematic Review and Meta-Analysis. Available at SSRN: https://ssrn.com/abstract=5098087 or http://dx.doi.org/10.2139/ssrn.5098087

Nathania Nathania

Airlangga University - Faculty of Medicine ( email )

Kiran T. Thakur (Contact Author)

Department of Neurology - Columbia University Irving Medical Center ( email )

Fransiskus Xaverius Rinaldi

Ende Regional General Hospital ( email )

Maulana Empitu

Airlangga University - Faculty of Medicine ( email )

Stevan Kristian Lionardi

Fatima Hospital ( email )