CHEMOTHERAPY OF INFECTIOUS DISEASES CAUSED BY INTRACELLULAR AGENTS Infectious Useful agents Diseases chemotherapeutic agents Bacteria

As is well known, effective chemotherapy is available for a large number of infectious diseases caused by bacteria multiplying extracellularly. Effective chemotherapy is also available for a considerable number of infectious diseases caused by intracellular agents. As shown in Table 1, typhoid fever and tuberculosis provide examples of treatable diseases caused by nonobligate intracellular bacterial agents. Diseases caused by rickettsiae, which are obligate intracellular parasites (e.g., epidemic typhus and Rocky Mountain spotted fever), respond satisfactorily to treatment with the various tetracyclines or chloramphenicol. Results obtained earlier with p-aminobenzoic acid were less impressive. Finally, treatment of psittacosis and lymphogranuloma venereum with the various tetracyclines also gives satisfactory results. Until recently the agents responsible for these and certain other diseases were classified with viruses. Actually, the Chlamydozoaceae, as this group of agents is now designated, seem to be more closely related to rickettsiae than to the so-called true viruses. The broad spectrum of effectiveness of the tetracyclines suggests that the therapeutic effects may be obtained through interference with a metabolic mechanism, probably biosynthetic, common to a wide variety of microbes. On the other hand, the parasite selective activity of p-aminobenzoic acid, penicillin, and sulfonamides emphasizes differences among the agents of epidemic typhus, psittacosis, and lymphogranuloma venereum. It is likely that these differences are also metabolic in nature. Available evidence indicates that the chemotherapeutic agents listed in Table 1 reduce the rate of multiplication of the various infectious agents. It is entirely possible, however, that in some instances the infecting agent is killed in the presence of the chemotherapeutic compound and not merely retarded. As the result of either mechanism, the number of infecting particles is kept relatively low. When the number is kept below a critical value for a given infection, symptoms and signs of disease may disappear or remain in abeyance.'3