Intrathecal Isoniazid in Tuberculous Meningitis

Swift, P. N.

doi:10.1136/adc.31.158.328

Cited by 6 publications

(9 citation statements)

References 15 publications

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“…Side effects were minimal, including non-specific meningeal irritation in one infant and major epileptic attacks in an adult with pre-existing conditions. This approach, combined with systemic therapy, was effective in reducing the need for frequent streptomycin injections, indicating most patients recovered fully or showed significant neurological improvement [ 107 ].…”

Section: Resultsmentioning

confidence: 99%

“…INH: Similarly, IT/IVT administration of INH, typically given thrice weekly at dosages between 5 to 100, proves highly effective with a mild side effect. Details of dosage and treatment duration are provided in Table 3 [ 24 , 105 , 107 , 108 , 109 , 110 , 111 , 112 ].…”

Section: Resultsmentioning

confidence: 99%

“…Nevertheless, the choice of administration route should also take into consideration patient-specific factors, such as condition, drug tolerance, and potential side effects. [22][23][24][105][106][107][108][109][110][111][112][120][121][122][123]. Some adverse events, such as infections, nerve damage, transient jaundice, seizures, etc., have been observed following the IT or IVT administration of RIF and INH [22][23][24][105][106][107][108][109][110][111][112][120][121][122][123].…”

Section: Pk Properties Of Anti-tb Drugsmentioning

confidence: 99%

“…[22][23][24][105][106][107][108][109][110][111][112][120][121][122][123]. Some adverse events, such as infections, nerve damage, transient jaundice, seizures, etc., have been observed following the IT or IVT administration of RIF and INH [22][23][24][105][106][107][108][109][110][111][112][120][121][122][123]. However, from our perspective, it is challenging to ascertain whether these side effects are directly attributable to RIF and INH or if they stem from disease progression or the specific procedure and route of administration.…”

Section: Pk Properties Of Anti-tb Drugsmentioning

confidence: 99%

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Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies

Madadi,

Sohn

2024

Pharmaceutics

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Tuberculous meningitis (TBM) presents a critical neurologic emergency characterized by high mortality and morbidity rates, necessitating immediate therapeutic intervention, often ahead of definitive microbiological and molecular diagnoses. The primary hurdle in effective TBM treatment is the blood–brain barrier (BBB), which significantly restricts the delivery of anti-tuberculous medications to the central nervous system (CNS), leading to subtherapeutic drug levels and poor treatment outcomes. The standard regimen for initial TBM treatment frequently falls short, followed by adverse side effects, vasculitis, and hydrocephalus, driving the condition toward a refractory state. To overcome this obstacle, intrathecal (IT) sustained release of anti-TB medication emerges as a promising approach. This method enables a steady, uninterrupted, and prolonged release of medication directly into the cerebrospinal fluid (CSF), thus preventing systemic side effects by limiting drug exposure to the rest of the body. Our review diligently investigates the existing literature and treatment methodologies, aiming to highlight their shortcomings. As part of our enhanced strategy for sustained IT anti-TB delivery, we particularly seek to explore the utilization of nanoparticle-infused hydrogels containing isoniazid (INH) and rifampicin (RIF), alongside osmotic pump usage, as innovative treatments for TBM. This comprehensive review delineates an optimized framework for the management of TBM, including an integrated approach that combines pharmacokinetic insights, concomitant drug administration strategies, and the latest advancements in IT and intraventricular (IVT) therapy for CNS infections. By proposing a multifaceted treatment strategy, this analysis aims to enhance the clinical outcomes for TBM patients, highlighting the critical role of targeted drug delivery in overcoming the formidable challenges presented by the blood–brain barrier and the complex pathophysiology of TBM.

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Section: Resultsmentioning

confidence: 99%

Section: Resultsmentioning

confidence: 99%

Section: Pk Properties Of Anti-tb Drugsmentioning

confidence: 99%

Section: Pk Properties Of Anti-tb Drugsmentioning

confidence: 99%

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Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies

Madadi,

Sohn

2024

Pharmaceutics

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“…In another study, Swift et al treated 18 TBM patients with IT isoniazid. CSF was sterilized in all patients and 16 out of 18 patients had good outcome [26]. Though these studies suggest that IT therapy could be effective in treating TBM patients, controlled studies are scarce.…”

Section: Discussionmentioning

confidence: 99%

Intrathecal therapy for tuberculous meningitis: propensity-matched cohort study

Wang

Wen

et al. 2021

Neurol Sci

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ObjectiveThe study aimed to determine the safety and efficacy of intrathecally administered isoniazid (INH) and prednisolone in addition to systemic anti-TB therapy and compare it with systemic anti-TB therapy alone in adult patients with tuberculous meningitis (TBM). Methods In this retrospective study, patients were categorized into two groups: Group A patients received systematic anti-TB therapy alone, Group B patients received IT INH (50 mg) and prednisolone (25 mg) twice a week together with the same standard systemic anti-TB therapy as Group A, in addition to the standard systemic anti-TB therapy. Functional outcomes were compared between the two groups in a prosperity-matched cohort using propensity score matching (PSM) method. Results A total of 198 patients with TBM were enrolled. After PSM, 30 patients from each group were analyzed, so that there was no significant difference in the characteristics of the two groups. Mortality at follow-up was significantly lower among patients receiving additional IT therapy (4/30, 13.3%) compared with matched patients receiving systemic anti-TB therapy alone (11/30, 36.7%, P value = 0.037). Conclusions In this propensity score-matched cohort, the addition of IT INH and prednisolone to systemic anti-TB therapy could be effective for the better outcome among adult TBM patients. Further large-scale, prospective, and randomized controlled trials are warranted to the best timing and indication of IT therapy.

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Intrathecal drug delivery of antibiotics

Mrowczynski

2023

Cerebrospinal Fluid and Subarachnoid Space

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Intrathecal Isoniazid in Tuberculous Meningitis

Cited by 6 publications

References 15 publications

Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies

Comprehensive Therapeutic Approaches to Tuberculous Meningitis: Pharmacokinetics, Combined Dosing, and Advanced Intrathecal Therapies

Intrathecal therapy for tuberculous meningitis: propensity-matched cohort study

Intrathecal drug delivery of antibiotics

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