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. 2022 Dec 12:13:1048653.
doi: 10.3389/fphar.2022.1048653. eCollection 2022.

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis

Nicole F Maranchick  1   2 , Mohammad H Alshaer  1   2 , Alison G C Smith  3 , Teona Avaliani  4 , Mariam Gujabidze  4 , Tinatin Bakuradze  4 , Shorena Sabanadze  4 , Zaza Avaliani  4 , Maia Kipiani  4   5 , Charles A Peloquin  1   2 , Russell R Kempker  6
Affiliations

Cerebrospinal fluid concentrations of fluoroquinolones and carbapenems in tuberculosis meningitis

Nicole F Maranchick et al. Front Pharmacol. .

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.

Keywords: antitubercular agents; carbapenems; cerebrospinal fluid; fluoroquinolones; pharmacokinetics; tuberculosis meningitis.

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Conflict of interest statement

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.

Figures

FIGURE 1
FIGURE 1
Carbapenem and fluoroquinolone CSF and serum concentrations over time from diagnosis. *The x-axis indicates the time in days from the start of any anti-tuberculosis treatment. Boxes indicate the median and interquartile range of the samples.
See this image and copyright information in PMC

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