Intensified Antituberculosis Therapy Regimen Containing Higher Dose Rifampin for Tuberculous Meningitis: A Systematic Review and Meta-Analysis

Abstract

BackgroundTuberculous meningitis is difficult to diagnose and is associated with high mortality. Recently, several studies evaluated the intensified regimen containing higher dose rifampin to treat tuberculous meningitis. However, this topic remains to be concluded. Therefore, this systematic review and meta-analysis was conducted to evaluate pharmacokinetics parameters, safety, and survival benefits of high-dose rifampin for tuberculous meningitis.MethodData were searched from PubMed, EMBASE, The Cochrane Library, and Web of Science for studies describing an antituberculosis regimen including a higher dose of rifampin for patients with tuberculous meningitis. The quality of eligible studies was evaluated via The Cochrane Risk of Bias Tool. The meta-analysis was performed by Review Manager 5.3 software, the synthesis of the data was shown in mean difference (MD) or relative risk (RR), and 95% confidence intervals (CIs).ResultsThere were six randomized control trails included in this meta-analysis. The results showed that the concentration in plasma and cerebrospinal fluid (CSF) were significantly higher in the intervention group than the standard group [MD = 22.08, 95%CI (16.24, 27.92), p < 0.00001; MD = 0.74, 95%CI (0.42, 1.05), p < 0.00001], as well as the area under the time concentration curve between 0 and 24 h (AUC0−24) of rifampin [MD 203.56, 95%CI (153.07, 254.05), p < 0.00001] in plasma, but the overall survival did not improve [RR = 0.92, 95%CI (0.67, 1.26), p = 0.61]. For adverse events, the results showed a statistically significant lower incidence of hypersensitivity compared with the intervention group [RR = 1.72, 95%CI (1.13, 2.62), p = 0.01]. Fortunately, other common adverse drug reactions such as liver injury, neurological events, myelosuppression, and cardiotoxicity had no significant increase [RR = 0.98, 95%CI (0.77, 1.26), p = 0.90; RR = 1.10, 95%CI (0.94, 1.30), p = 0.23; RR = 0.82, 95%CI (0.59, 1.13), p = 0.22; RR = 1.11, 95%CI (0.66, 1.86), p = 0.70].ConclusionThis meta-analysis suggested that the intensified treatment regimen including a higher dose of rifampin significantly increased the rifampin concentration both in the plasma and CSF, and it was safe in patients with tuberculous meningitis, but resulted in no improvement in survival rates.

Proposing Intranasal Rifampin for Alzheimer’s Disease and the Other Age-Related Neurodegenerative Proteinopathies

“…Notwithstanding the known hepatic risk, rifampin has been given in much higher doses for rifampin-sensitive tuberculosis [25,26] and particularly for tuberculous meningitis [16]. The rifampin standard-of-care oral dose is 10 mg/kg with increase dosage ranging to 35 mg/kg and intravenous dosing at 20 mg/kg.…”

Mathematical Model for Growth and Rifampicin-Dependent Killing Kinetics of Escherichia coli Cells

“…It is still on the World Health Organization’s List of Essential Medicines. Rifampicin inhibits bacterial DNA-dependent RNA polymerase and suppresses RNA synthesis to kill bacteria. , It is widely used for the treatment of tuberculosis, leprosy, acute bacterial meningitis, − pneumonia, , and biofilm-related infections. , In pursuit of enhanced therapeutic outcomes, several clinical and computational studies have been conducted to shorten the therapy time, increase its effectiveness, and reduce the negative side effects and financial costs of rifampicin. , In the context of antibiotic administration, generally, lower cure rates can be attributed to the increased emergence of resistance within infections . Nonetheless, when tolerability and safety of the elevated dosages of rifampicin are achieved, it might contribute to the management of infections with high mortality rates.…”

“… 21 , 22 In pursuit of enhanced therapeutic outcomes, several clinical and computational studies have been conducted to shorten the therapy time, increase its effectiveness, and reduce the negative side effects and financial costs of rifampicin. 23 , 24 In the context of antibiotic administration, generally, lower cure rates can be attributed to the increased emergence of resistance within infections. 25 Nonetheless, when tolerability and safety of the elevated dosages of rifampicin are achieved, it might contribute to the management of infections with high mortality rates.…”

“…These strategies can be discovery of an antibiotic, , invention of an alternative to antibiotics, − or reformulation of the administration of current antibiotics by a better understanding of bacterial behavior. , Currently, a limited number of antibiotics are in the treatment repertoire existing for bacterial infections . Among them, rifampicin is one of the essentials that has been used for the treatment of various mycobacterial and Gram-positive bacterial infections. − In the literature, several clinical and computational studies have been conducted to shorten therapy time, increase effectiveness, and reduce the negative side effects and financial costs of rifampicin treatments. , Several lines of evidence suggest that under conditions of tolerability and safety, intensified regimens incorporating elevated dosages of rifampicin may shorten the treatment duration or contribute to the management of infections linked to high mortality rates. Nevertheless, a consensus remains elusive regarding assessing pharmacokinetic parameters, efficacy clarification, and compound toxicity.…”

“… 14 − 22 In the literature, several clinical and computational studies have been conducted to shorten therapy time, increase effectiveness, and reduce the negative side effects and financial costs of rifampicin treatments. 23 , 24 Several lines of evidence suggest that under conditions of tolerability and safety, intensified regimens incorporating elevated dosages of rifampicin may shorten the treatment duration or contribute to the management of infections linked to high mortality rates. Nevertheless, a consensus remains elusive regarding assessing pharmacokinetic parameters, efficacy clarification, and compound toxicity.…”