Intensified antibiotic treatment of tuberculosis meningitis

Cresswell, Fiona V; Brake, Lindsey te; Atherton, Rachel R.; Ruslami, Rovina; Dooley, Kelly E.; Aarnoutse, Rob E.; Crevel, Reinout van

doi:10.1080/17512433.2019.1552831

Cited by 37 publications

(24 citation statements)

References 168 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…The current choice of drugs and their dosing is based upon the treatment of pulmonary tuberculosis, but the distribution of some of the drugs into the brain is restricted by the blood‐brain barrier, which may result in suboptimal drug exposures, bacterial killing, and treatment outcomes. Thus, it is hypothesized that bacterial killing and clinical outcomes from TBM can be improved by increasing the doses of some drugs, in particular rifampin, and by using drugs which cross the blood‐brain barrier freely …”

mentioning

confidence: 99%

“…Thus, it is hypothesized that bacterial killing and clinical outcomes from TBM can be improved by increasing the doses of some drugs, in particular rifampin, and by using drugs which cross the blood-brain barrier freely. 2 We recently tested this hypothesis in a randomized controlled trial comparing the standard four-drug antituberculosis regimen (using 10 mg/kg/day rifampin) with a five-drug "intensive" regimen that included higher dose rifampin (15 mg/kg/ day) and the addition of levofloxacin (1,000 mg/kg/day) for the first 2 months of TBM treatment. 3 The trial randomized 817…”

mentioning

confidence: 99%

See 1 more Smart Citation

Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis

Ding

Thuong

Pham

et al. 2020

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

The most effective antituberculosis drug treatment regimen for tuberculous meningitis is uncertain. We conducted a randomized controlled trial comparing standard treatment with a regimen intensified by rifampin 15 mg/kg and levofloxacin for the first 60 days. The intensified regimen did not improve survival or any other outcome. We therefore conducted a nested pharmacokinetic/pharmacodynamic study in 237 trial participants to define exposure–response relationships that might explain the trial results and improve future therapy. Rifampin 15 mg/kg increased plasma and cerebrospinal fluid (CSF) exposures compared with 10 mg/kg: day 14 exposure increased from 48.2 hour·mg/L (range 18.2–93.8) to 82.5 hour·mg/L (range 8.7–161.0) in plasma and from 3.5 hour·mg/L (range 1.2–9.6) to 6.0 hour·mg/L (range 0.7–15.1) in CSF. However, there was no relationship between rifampin exposure and survival. In contrast, we found that isoniazid exposure was associated with survival, with low exposure predictive of death, and was linked to a fast metabolizer phenotype. Higher doses of isoniazid should be investigated, especially in fast metabolizers.

show abstract

mentioning

confidence: 99%

mentioning

confidence: 99%

Pharmacokinetics and Pharmacodynamics of Intensive Antituberculosis Treatment of Tuberculous Meningitis

Ding

Thuong

Pham

et al. 2020

Clin Pharma and Therapeutics

View full text Add to dashboard Cite

show abstract

“…Tuberculosis (TB) is a global health emergency, leading to more than 10 million new cases and an estimated 1.6 million deaths in 2017 1 . Tuberculous meningitis (TBM) only makes up a small proportion of TB cases (1-2%, probably more in human immunodeficiency [HIV]-endemic settings) but disproportionally contributes to TB-associated mortality 2 . Up to 50% of TBM patients in published studies die, and mortality is substantially higher among those with drug-resistant TB or HIV co-infection 2 .…”

Section: Introductionmentioning

confidence: 99%

“…Tuberculous meningitis (TBM) only makes up a small proportion of TB cases (1-2%, probably more in human immunodeficiency [HIV]-endemic settings) but disproportionally contributes to TB-associated mortality 2 . Up to 50% of TBM patients in published studies die, and mortality is substantially higher among those with drug-resistant TB or HIV co-infection 2 . An unknown proportion of TBM patients even die before diagnosis is made or treatment is started.…”

Section: Introductionmentioning

confidence: 99%

“…Research aimed at improving outcome on TBM mainly focuses on better diagnosis 6-8 , drug treatment 2,9,10 and supportive care for patients in hospital 11 , rather than on the patient's journey from the moment he or she develops symptoms until no further care is needed. In the absence of empirical data, we aim to provide a theoretical framework that may help identify barriers and challenges in providing optimal care for TBM patients, by combining cascade of care, patient pathway and health needs analyses.…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Establishing the cascade of care for patients with tuberculous meningitis

et al. 2020

Self Cite

View full text Add to dashboard Cite

Meningitis is a relatively rare form of tuberculosis, but it carries a high mortality rate, reaching 50% in some settings, with higher rates among patients with HIV co-infection and those with drug-resistant disease. Most studies of tuberculosis meningitis (TBM) tend to focus on better diagnosis, drug treatment and supportive care for patients in hospital. However, there is significant variability in mortality between settings, which may be due to specific variation in the availability and quality of health care services, both prior to, during, and after hospitalization. Such variations have not been studied thoroughly, and we therefore present a theoretical framework that may help to identify where efforts should be focused in providing optimal services for TBM patients. As a first step, we propose an adjusted cascade of care for TBM and patient pathway studies that might help identify factors that account for losses and delays across the cascade. Many of the possible gaps in the TBM cascade are related to health systems factors; we have selected nine domains and provide relevant examples of systems factors for TBM for each of these domains that could be the basis for a health needs assessment to address such gaps. Finally, we suggest some immediate action that could be taken to help make improvements in services. Our theoretical framework will hopefully lead to more health system research and improved care for patients suffering from this most dangerous form of tuberculosis.

show abstract