In this study the compounds levofloxacin and sparfloxacin, as well as three experimental compounds (AMQ2, AMQ4, and AMQ5), were compared with isoniazid and rifabutin in terms of their capacity to inhibit the intracellular growth of the drug-susceptible Mycobacterium tuberculosis strain Erdman and the isoniazid-resistant katG gene-negative strain 24 within monolayers of mouse bone marrow-derived macrophages. Both levofloxacin and sparfloxacin, as well as compound AMQ4, had substantial activity in this physiologically relevant model, further confirming the potential usefulness of this class of compounds in the therapy of tuberculosis.