Tuberculosis treatment for the beginning of the next century

As we move into the next century it appears that new antituberculosis drugs will arise from four categories: 1) new use of old drugs, 2) new delivery of old drugs, 3) new drugs within old classes, and 4) new classes of drugs. Old drugs such as clofazimine and its analogues, rifabutin, the macrolides, aminoglycosides, quinolones and perhaps vitamin D may find a way into better regimens. New therapy may also arise from new combinations and new uses of current antituberculosis drugs. New drugs are being developed in the rifamycin, fluoroquinolone, and nitroimidazole families. Several immune amplifiers, such as interferon-gamma (IFN-gamma), interleukin-2 (IL-2), and interleukin-12 (IL-12) have undergone pilot testing. Counteracting adhesion molecules is being tested for several infectious diseases. With the unraveling of the tuberculosis genome, attacking enzymes unique to Mycobacterium tuberculosis is easier and allows us to hit elements in both a metabolic pathway and its alternate pathway. Interfering with transcription factors that bind DNA but do not promote RNA production could interrupt transcription. Genetic products of mycobacteria can be modified to cause their own death. Phages may deliver antisense nucleic acids for inhibition of mycobacterial gene expression. The distinction between drugs, immunotherapies and vaccines may blur.