Rifabutin Central Nervous System Concentrations in a Rabbit Model of Tuberculous Meningitis

Overview

Journal Antimicrob Agents Chemother

Publisher American Society for Microbiology

Specialty Pharmacology

Date 2024 Jul 19

PMID 39028192

Authors

Sean Wasserman

Rosleine Antilus-Sainte

Noha Abdelgawad

Narineh M Odjourian

Melissa Cristaldo

Maureen Dougher

Firat Kaya

Matthew Zimmerman

Paolo Denti

Martin Gengenbacher

Affiliations

Soon will be listed here.

Abstract

Tuberculous meningitis (TBM) has a high mortality, possibly due to suboptimal therapy. Drug exposure data of antituberculosis agents in the central nervous system (CNS) are required to develop more effective regimens. Rifabutin is a rifamycin equivalently potent to rifampin in human pulmonary tuberculosis. Here, we show that human-equivalent doses of rifabutin achieved potentially therapeutic exposure in relevant CNS tissues in a rabbit model of TBM, supporting further evaluation in clinical trials.

References

Lan T, Ganapathy U, Sharma S, Ahn Y, Zimmerman M, Molodtsov V . Redesign of Rifamycin Antibiotics to Overcome ADP-Ribosylation-Mediated Resistance. Angew Chem Int Ed Engl. 2022; 61(45):e202211498. PMC: 9633546. DOI: 10.1002/anie.202211498. View

Zhang Y, Huo M, Zhou J, Xie S . PKSolver: An add-in program for pharmacokinetic and pharmacodynamic data analysis in Microsoft Excel. Comput Methods Programs Biomed. 2010; 99(3):306-14. DOI: 10.1016/j.cmpb.2010.01.007. View

Sirgel F, Warren R, Bottger E, Klopper M, Victor T, van Helden P . The rationale for using rifabutin in the treatment of MDR and XDR tuberculosis outbreaks. PLoS One. 2013; 8(3):e59414. PMC: 3602005. DOI: 10.1371/journal.pone.0059414. View

Tsenova L, Ellison E, Harbacheuski R, Moreira A, Kurepina N, Reed M . Virulence of selected Mycobacterium tuberculosis clinical isolates in the rabbit model of meningitis is dependent on phenolic glycolipid produced by the bacilli. J Infect Dis. 2005; 192(1):98-106. DOI: 10.1086/430614. View

Ji B, Truffot-Pernot C, Lacroix C, Raviglione M, OBrien R, Olliaro P . Effectiveness of rifampin, rifabutin, and rifapentine for preventive therapy of tuberculosis in mice. Am Rev Respir Dis. 1993; 148(6 Pt 1):1541-6. DOI: 10.1164/ajrccm/148.6_Pt_1.1541. View

Davies G, Cerri S, Richeldi L . Rifabutin for treating pulmonary tuberculosis. Cochrane Database Syst Rev. 2007; (4):CD005159. PMC: 6532710. DOI: 10.1002/14651858.CD005159.pub2. View

Heifets L, Iseman M . Rifabutine: minimal inhibitory and bactericidal concentrations for Mycobacterium tuberculosis. Am Rev Respir Dis. 1988; 137(3):719-21. DOI: 10.1164/ajrccm/137.3.719. View

Yunivita V, Dian S, Ganiem A, Hayati E, Achmad T, Dewi A . Pharmacokinetics and safety/tolerability of higher oral and intravenous doses of rifampicin in adult tuberculous meningitis patients. Int J Antimicrob Agents. 2016; 48(4):415-21. DOI: 10.1016/j.ijantimicag.2016.06.016. View

Lanni F, Antilus Sainte R, Hansen Jr M, Parigi P, Kaya F, LoMauro K . A preclinical model of TB meningitis to determine drug penetration and activity at the sites of disease. Antimicrob Agents Chemother. 2023; 67(12):e0067123. PMC: 10720511. DOI: 10.1128/aac.00671-23. View

10.

Svensson E, Dian S, Te Brake L, Ganiem A, Yunivita V, van Laarhoven A . Model-Based Meta-analysis of Rifampicin Exposure and Mortality in Indonesian Tuberculous Meningitis Trials. Clin Infect Dis. 2019; 71(8):1817-1823. PMC: 7643733. DOI: 10.1093/cid/ciz1071. View

11.

Ruslami R, Ganiem A, Dian S, Apriani L, Achmad T, van der Ven A . Intensified regimen containing rifampicin and moxifloxacin for tuberculous meningitis: an open-label, randomised controlled phase 2 trial. Lancet Infect Dis. 2012; 13(1):27-35. DOI: 10.1016/S1473-3099(12)70264-5. View

12.

Maitre T, Bonnet M, Calmy A, Raberahona M, Rakotoarivelo R, Rakotosamimanana N . Intensified tuberculosis treatment to reduce the mortality of HIV-infected and uninfected patients with tuberculosis meningitis (INTENSE-TBM): study protocol for a phase III randomized controlled trial. Trials. 2022; 23(1):928. PMC: 9640846. DOI: 10.1186/s13063-022-06772-1. View

13.

Siegal F, Eilbott D, Burger H, Gehan K, Davidson B, Kaell A . Dose-limiting toxicity of rifabutin in AIDS-related complex: syndrome of arthralgia/arthritis. AIDS. 1990; 4(5):433-41. DOI: 10.1097/00002030-199005000-00009. View

14.

Strolin Benedetti M, Pianezzola E, Brughera M, Fraier D, CASTELLI M . Concentrations of rifabutin in plasma and cerebrospinal fluid in cynomolgus monkeys. J Antimicrob Chemother. 1994; 34(4):600-3. DOI: 10.1093/jac/34.4.600. View

15.

Lan N, Thu N, Barrail-Tran A, Duc N, Lan N, Laureillard D . Randomised pharmacokinetic trial of rifabutin with lopinavir/ritonavir-antiretroviral therapy in patients with HIV-associated tuberculosis in Vietnam. PLoS One. 2014; 9(1):e84866. PMC: 3898920. DOI: 10.1371/journal.pone.0084866. View

16.

Weiner M, Benator D, Burman W, Peloquin C, Khan A, Vernon A . Association between acquired rifamycin resistance and the pharmacokinetics of rifabutin and isoniazid among patients with HIV and tuberculosis. Clin Infect Dis. 2005; 40(10):1481-91. DOI: 10.1086/429321. View

17.

Dodd P, Osman M, Cresswell F, Stadelman A, Lan N, Thuong N . The global burden of tuberculous meningitis in adults: A modelling study. PLOS Glob Public Health. 2023; 1(12):e0000069. PMC: 10021871. DOI: 10.1371/journal.pgph.0000069. View

18.

Cresswell F, Meya D, Kagimu E, Grint D, Te Brake L, Kasibante J . High-Dose Oral and Intravenous Rifampicin for the Treatment of Tuberculous Meningitis in Predominantly Human Immunodeficiency Virus (HIV)-Positive Ugandan Adults: A Phase II Open-Label Randomized Controlled Trial. Clin Infect Dis. 2021; 73(5):876-884. PMC: 8423465. DOI: 10.1093/cid/ciab162. View

19.

Grassi C, Peona V . Use of rifabutin in the treatment of pulmonary tuberculosis. Clin Infect Dis. 1996; 22 Suppl 1:S50-4. DOI: 10.1093/clinids/22.supplement_1.s50. View

20.

Tucker E, Guglieri-Lopez B, Ordonez A, Ritchie B, Klunk M, Sharma R . Noninvasive C-rifampin positron emission tomography reveals drug biodistribution in tuberculous meningitis. Sci Transl Med. 2018; 10(470). PMC: 6360528. DOI: 10.1126/scitranslmed.aau0965. View