Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis.

Autor:	Maranchick NF; Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, United States., Alshaer MH; Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, United States., Smith AGC; Department of Medicine, Division of Internal Medicine, Duke University, Durham, NC, United States., Avaliani T; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia., Gujabidze M; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia., Bakuradze T; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia., Sabanadze S; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia., Avaliani Z; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia., Kipiani M; National Center for Tuberculosis and Lung Diseases, Tbilisi, Georgia.; David Tvildiani Medical University, Tbilisi, Georgia., Peloquin CA; Infectious Disease Pharmacokinetics Lab, Emerging Pathogens Institute, University of Florida, Gainesville, FL, United States.; Department of Pharmacotherapy and Translational Research, College of Pharmacy, University of Florida, Gainesville, FL, United States., Kempker RR; Department of Medicine, Division of Infectious Diseases, Emory University, Atlanta, GA, United States.
Jazyk:	angličtina
Zdroj:	Frontiers in pharmacology [Front Pharmacol] 2022 Dec 12; Vol. 13, pp. 1048653. Date of Electronic Publication: 2022 Dec 12 (Print Publication: 2022).
DOI:	10.3389/fphar.2022.1048653
Abstrakt:	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. Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest. (Copyright © 2022 Maranchick, Alshaer, Smith, Avaliani, Gujabidze, Bakuradze, Sabanadze, Avaliani, Kipiani, Peloquin and Kempker.)
Databáze:	MEDLINE
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