The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis.

Phuapradit, P; Supmonchai, K; Kaojarern, Sming; Mokkhavesa, Chintana

doi:10.1136/jnnp.53.1.81

Cited by 26 publications

(9 citation statements)

References 8 publications

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“…Some have advocated for longer treatment (64,66), while others have supported a short course of 6 to 9 months (50, 74, 156, 228). Both isoniazid and pyrazinamide pass easily across the BBB (54,55,84,155), and isoniazid remains the backbone of TBM treatment. Rifampin and ethambutol have significantly less penetration into the CNS (54, 84), although they still play an important role in the treatment of CNS tuberculosis (139).…”

Section: Antibiotic Therapymentioning

confidence: 99%

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

et al. 2008

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SUMMARY Tuberculosis of the central nervous system (CNS) is a highly devastating form of tuberculosis, which, even in the setting of appropriate antitubercular therapy, leads to unacceptable levels of morbidity and mortality. Despite the development of promising molecular diagnostic techniques, diagnosis of CNS tuberculosis relies largely on microbiological methods that are insensitive, and as such, CNS tuberculosis remains a formidable diagnostic challenge. Insights into the basic neuropathogenesis of Mycobacterium tuberculosis and the development of an appropriate animal model are desperately needed. The optimal regimen and length of treatment are largely unknown, and with the rising incidence of multidrug-resistant strains of M. tuberculosis, the development of well-tolerated and effective antibiotics remains a continued need. While the most widely used vaccine in the world largely targets this manifestation of tuberculosis, the BCG vaccine has not fulfilled the promise of eliminating CNS tuberculosis. We put forth this review to highlight the current understanding of the neuropathogenesis of M. tuberculosis, to discuss certain epidemiological, clinical, diagnostic, and therapeutic aspects of CNS tuberculosis, and also to underscore the many unmet needs in this important field.

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Section: Antibiotic Therapymentioning

confidence: 99%

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

et al. 2008

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“…Currently, studies indicate that isoniazid is the only antituberculosis drug which can permeate the BCB with almost the same concentration in CSF and plasma [12]. Animal experiments proved that the concentrations of rifampicin, ethambutol and pyrazinamide increased in the CSF after damage to the BCB [13,14]. Studies have proved that the antibacteria effect as well as the permeability of the BCB correlated positively with the recovery rate in bacterial meningitis [15,16].…”

Section: Discussionmentioning

confidence: 99%

The Association between Blood-Cerebrospinal Fluid Barrier Dysfunction and the Therapeutic Effect in Tuberculous Meningitis Patients

Tang

An²,

Liao³

et al. 2014

Eur Neurol

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Objective: To explore the correlation of blood-cerebrospinal fluid (CSF) barrier (BCB) dysfunction with the therapeutic effect of antitubercular agents and their resistance, hoping to provide theoretical evidence for improvement of the therapeutic effect. Methods: Albumin in CSF and serum was assayed by IMMAGE. The CSF/serum albumin ratio (Q_ALB) was used to evaluate the permeability of the BCB. Real-time fluorescence quantitative PCR was used to detect the amount of Mycobacterium tuberculosis DNA, and an MTBDRplus reagent kit was used to determine the type of drug resistance of the M. tuberculosis.Results: The correlation analysis showed that significant correlation existed between the grade of severity of tuberculous meningitis and the Q_ALB, and the grade of severity and the total leukocyte count in the CSF, for which the correlation coefficients were 0.366 (p < 0.05) and 0.365 (p < 0.05), respectively. The Q_ALB in the group of patients who recovered was significantly higher than that in those patients who experienced disease progression (p = 0.019). Conclusions: Our study showed that the permeability of the BCB correlated with the cure rate in tuberculous meningitis. Specifically, in the treatment of tuberculous meningitis, it is of key importance to utilize the benefit of the permeability of the BCB to achieve a better outcome.

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“…[36] CSF : serum concentration ratios were between 0.87 and 1.05 in 17 adult patients (15 to 70 years of age) after up to 6 months of pyrazinamide therapy. [37] Pyrazinamide is about 50% protein bound and undergoes hepatic metabolism. First, pyrazinamide is hydrolysed to pyrazinoic acid by pyrazinamide deaminidase and then pyrazinoic acid is hydroxylated to 5-hydroxypyrazinoic acid by xanthine oxidase.…”

Section: Pharmacokineticsmentioning

confidence: 99%

Treatment of Tuberculous Infection and Disease in Children

Stowe

Jacobs

1999

Pediatric Drugs

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The standard preventive therapy for paediatric patients with tuberculous infection centres on isoniazid therapy. The chosen regimen of isoniazid therapy is based on individual patient factors. In the case of known or suspected resistance, combination therapy [e.g. isoniazid and rifampicin (rifampin)] or alternative therapies (e.g. pyrazinamide, a fluoroquinolone and/or ethambutol) should be employed. The goal of treatment of tuberculous disease is to achieve sterilisation in the shortest possible time. More intensive multiple drug combination regimens (e.g. isoniazid, rifampicin and pyrazinamide) have resulted in successful 6- and 9-month treatment regimens in children. If drug resistance is suspected then a fourth drug is added to the initial treatment regimen and the length of therapy may be extended to 18 months. The paediatric information available on the commonly used antituberculous agents (e.g. isoniazid, rifampicin, pyrazinamide and ethambutol) is reviewed in this article. Agents are described with an emphasis on their formulation availability, mechanism of action, pharmacokinetic properties (e.g. absorption, distribution, metabolism and elimination), adverse effects, and interactions (e.g. drug-drug, drug-food and drug-disease).

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The blood/cerebrospinal fluid partitioning of pyrazinamide: a study during the course of treatment of tuberculous meningitis.

Cited by 26 publications

References 8 publications

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

Central Nervous System Tuberculosis: Pathogenesis and Clinical Aspects

The Association between Blood-Cerebrospinal Fluid Barrier Dysfunction and the Therapeutic Effect in Tuberculous Meningitis Patients

Treatment of Tuberculous Infection and Disease in Children

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