Effectiveness of Ofloxacin againstMycobacterium tuberculosisandMycobacterium avium, and Rifampin againstM. tuberculosisin Cultured Human Macrophages

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Abstract
Ofloxacin (OFL) is a new broad-spectrum drug with potentially valuable antimycobacterial activity. It was tested for ability to inhibit virulent tubercle bacilli (TB) and virulent Mycobacterium avium in cultured human macrophages (MP). The first-line antituberculosis drug rifampin (RMP) also was tested against TB in MP. The drugs were added to the MP cultures immediately after infection or 2 days later. Antimicrobial inhibition was measured by colony-forming-unit (cfu) counts of bacilli from lysed samples of the infected MP taken at zero, 4, and 7 days after infection. Drug inhibition of the bacteria in vitro in 7H9 broth also was measured. OFL showed the same minimal inhibitory concentration (MIC) of 1.25 .mu.g/ml against TB in vitro and in MP. At 2 .mu.g/ml or more it killed TB in vitro and in MP. It was equally effective in MP against initially nonmultiplying TB and MP-established TB, which were multiplying exponentially in the MP. OFL had the same MIC in vitro against M. avium but was ineffective against both M. avium in MP and M. avium isolated directly from MP at as much as 8 .mu.g/ml. The MIC for RMP against TB in MP was 0.1 .mu.g/ml, and TB in vitro 0.02 .mu.g/ml. At 0.5 .mu.g/ml or greater, it killed TB in MP. RMP killed TB in MP rapidly, whereas OFL killed them slowly. These results confirm initial clinical evidence, as published by others, that OFL should be a useful antituberculosis drug. However, they suggest that it may not be very effective against MA infections. They confirm the well-known, excellent antituberculosis effectiveness of RMP and provide some new information that helps explain why RMP produces relapse-free cures better than isoniazid doses.