Studies of antituberculosis chemotherapy with an in vitro model of human tuberculosis

Abstract

Testing new drugs or drug combinations for activity against tuberculosis is highly problematic: Clinical therapy trials are expensive and time-consuming; animal trial results may not be applicable to humans; and simple in vitro testing on culture medium excludes a vital component of the natural infection, namely the macrophage. Described here is a technique to treat with chemotherapy human macrophages that have been infected ex vivo with tubercle bacilli. Briefly discussed are the results of treating such infected phagocytes with a variety of agents: Streptomycin, ethambutol, pyrazinamide, isoniazid, and ceforanide. Interesting parallels between the macrophage-model results and observed clinical phenomena are noted. This model appears to have considerable potential for evaluating drug activity against tubercle bacilli, nontuberculous mycobacteria, and, perhaps, other intracellular parasites.