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Until recently, the outlook for patients with drug-resistant TB could not have been gloomier. The last major anti-TB drug, rifampin, was approved more than a quarter-century ago. In the interim, the TB bacillus has managed to develop resistance to the cocktail of drugs physicians have long used to treat it, including that old standby streptomycin. New drugs, with different mechanisms of action, would be a great help, particularly if they shortened the present six months' time required for treatment. The linezolid family, for example, appears to hold some promise, as does a compound the Seattle-based PathoGenesis Corp. is investigating.
The process of discovering antimicrobials should speed up, thanks to the rapid sequencing of the genomes of disease-causing organisms. Among the latest conquests are the bacteria responsible for causing syphilis and leprosy. The genome of the parasite that causes malaria is also beginning to yield its secrets, including the exact genetic mutations that confer chloroquine resistance. Scientists are beginning to exploit what they know about the parasite's life cycle after it invades the red blood cells of the human body. Daniel Goldberg, a malaria researcher at the Howard Hughes Medical Institute in Chevy Chase, Md., is trying to figure out how to block the parasite's digestion of hemoglobin and thereby cause it to starve.
The microbes that cause such diseases as TB and malaria will never stop evolving, warns Columbia University epidemiologist Dr. Stephen Morse, and they will develop resistance to the next generation of miracle drugs just as they did in the past. How fast they do so is in large part up to us. With antibiotics, too little is not a good thing, observes Morse, and neither is too much. Unless we devise a formula that is just right, he predicts, we will forever be frantically racing to catch up with our nimbler microbial foes.
--With reporting by Sora Song/New York