Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis

• Type of Material: Article
• Authors: Nicole F Maranchick, University of Florida; Mohammad H Alshaer, University of Florida; Alison GC Smith, Duke University; Teona Avaliani, National Center for Tuberculosis and Lung Diseases; Mariam Gujabidze, National Center for Tuberculosis and Lung Diseases; Tinatin Bakuradze, National Center for Tuberculosis and Lung Diseases; Shorena Sabanadze, National Center for Tuberculosis and Lung Diseases; Zaza Avaliani, National Center for Tuberculosis and Lung Diseases; Maia Kipiani, National Center for Tuberculosis and Lung Diseases; Charles A Peloquin, University of Florida; Russell Kempker, Emory University
• Language: English
• Date: 2022-12-12
• Publisher: FRONTIERS MEDIA SA
• Publication Version: Final Published Version
• Copyright Statement: © 2022 Maranchick, Alshaer, Smith, Avaliani, Gujabidze, Bakuradze, Sabanadze, Avaliani, Kipiani, Peloquin and Kempker.
• License: Creative Commons Attribution 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.3389/fphar.2022.1048653
• Title of Journal or Parent Work: FRONTIERS IN PHARMACOLOGY
• Volume: 13
• Start Page: 1048653
• End Page: 1048653
• Grant/Funding Information: This work was supported in part by the National Institutes of Health (NIH) including the Fogarty International Center (D43 TW007124) and National Institute of Allergy and Infectious Diseases (R03 AI139871, K23AI103044, TL1TR002382, UL1TR002378, and P30AI168386).
• Keywords: carbapenems; IMIPENEM; CLAVULANATE; Life Sciences & Biomedicine; OFLOXACIN; cerebrospinal fluid; tuberculosis meningitis; PHARMACOKINETICS; Pharmacology & Pharmacy; pharmacokinetics; MYCOBACTERIUM-TUBERCULOSIS; PLASMA; PERFORMANCE LIQUID-CHROMATOGRAPHY; Science & Technology; NEUROTOXICITY; fluoroquinolones; antitubercular agents; ANTIBIOTICS; PHARMACODYNAMICS
• Research Categories: Health Sciences, Pharmacology; Health Sciences, Medicine and Surgery

Abstract

Background: Tuberculosis meningitis (TBM) is the most lethal form of TB. It is difficult to treat in part due to poor or uncertain drug penetration into the central nervous system (CNS). To help fill this knowledge gap, we evaluated the cerebrospinal fluid (CSF) concentrations of fluoroquinolones and carbapenems in patients being treated for TBM. Methods: Serial serum and CSF samples were collected from hospitalized patients being treated for TBM. CSF was collected from routine lumbar punctures between alternating timepoints of 2 and 6 h after drug administration to capture early and late CSF penetration. Rich serum sampling was collected after drug administration on day 28 for non-compartmental analysis. Results: Among 22 patients treated for TBM (8 with confirmed disease), there was high use of fluoroquinolones (levofloxacin, 21; moxifloxacin, 10; ofloxacin, 6) and carbapenems (imipenem, 11; meropenem, 6). Median CSF total concentrations of levofloxacin at 2 and 6 h were 1.34 mg/L and 3.36 mg/L with adjusted CSF/serum ratios of 0.41 and 0.63, respectively. For moxifloxacin, the median CSF total concentrations at 2 and 6 h were 0.78 mg/L and 1.02 mg/L with adjusted CSF/serum ratios of 0.44 and 0.62. Serum and CSF concentrations of moxifloxacin were not affected by rifampin use. Among the 76 CSF samples measured for carbapenem concentrations, 79% were undetectable or below the limit of detection. Conclusion: Fluoroquinolones demonstrated high CSF penetration indicating their potential usefulness for the treatment of TBM. Carbapenems had lower than expected CSF concentrations.