Most of the fluoroquinolones antibiotics (see Chapter 44) have activity against M. tuberculosis and M. avium-intracellulare. Ciprofloxacin, ofloxacin, and levofloxacin inhibit 90% of the strains of susceptible tubercula bacilli at concentrations of less than 2 ^g/mL. Levofloxacin is preferred because it is the active l-optical isomer of ofloxacin and is approved for once-daily use. The quinolones act by inhibition of bacterial DNA gyrase. Resistance is the result of spontaneous mutations in genes that either change the DNA gyrase or decrease the ability of the drug to cross the cell membrane.
Quinolones are important recent additions to the therapeutic agents used against M. tuberculosis, especially in MDR strains. Clinical trials of ofloxacin in combination with isoniazid and rifampin have indicated activity comparable to that of ethambutol. In addition, quinolones, particularly ciprofloxacin, are used as part of a combined regimen in HIV-infected patients.
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