Fluoroquinolones for the treatment of tuberculosis in children
Abstract
The fluoroquinolones are key components of current multidrug-resistant tuberculosis (MDR-TB) treatment regimens and are being evaluated in shortened treatment regimens as well as in the prevention of drug-resistant TB. The objective of this review was to identify existing evidence for the use of the fluoroquinolones ofloxacin, levofloxacin and moxifloxacin in the treatment of TB in children. Existing data from in vitro, animal and human studies consistently demonstrate the efficacy of the fluoroquinolones against Mycobacterium tuberculosis, with superiority of levofloxacin and moxifloxacin compared to ofloxacin. In vitro and murine studies demonstrated the potential of moxifloxacin to shorten drug-susceptible TB treatment, but in multiple randomized controlled trials shortened fluoroquinolone-containing regimens have not been non-inferior compared to standard therapy. Resistance occurs frequently via mutations in the gyrA gene, and emerges rapidly depending on the fluoroquinolone concentration, with newer more potent fluoroquinolones less likely to develop resistance. Emerging data from paediatric studies underlines the importance of fluoroquinolones in the treatment of MDR-TB in children. There is a paucity of pharmacokinetic data especially in children <5 years of age and HIV-infected children; existing studies show substantially lower serum concentrations in children compared to adults at currently recommended doses, probably due to faster elimination. This has…
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