Intracellular infection and the carrier state.

The evidence summarized in this article is sufficient to support conclusions as follows. 1) Antibiotics penetrate rapidly into mammalian cells and inhibit multiplication of susceptible microbes within the cell as promptly and effectively as they inhibit multiplication of such microbes outside the cell. This is consistent with clinical experience. 2) Death of individual organisms inside mammalian cells bathed in medium containing antibiotics continues over several weeks but may not proceed pari passu with time. This observation supports the as yet meager clinical data, which suggest that eradication of the typhoid carrier state may be accomplished through antibiotic therapy, provided (i) the proper antibiotic is selected; (ii) it is administered in amounts sufficient to obtain continuous suppression of growth of intracellular organisms; and (iii) the regimen is maintained for 2 or 3 weeks. 3) The actual cause of death and destruction of intracellular microbes in treated cells remains an enigma. To attribute this to inanition or senescence of the organisms, without describing mechanisms, is to avoid the issue. The hypotheses dealing with inactivation of intracellular microbes by intracellular antimicrobial substances and antibodies deserve to be explored. 4) Evidence from the ward and laboratory suggests that infected cells can clear themselves of invading pathogens and recover. Although antibiotics have played the major role in demonstrating this in the laboratory, it is possible that they do nothing more than hold the intruders in abeyance while natural defense mechanisms of the cell gain the upper hand. Certainly such cellular mechanisms must provide a potent force for survival; otherwise, why would 98 percent of typhoid patients fail to become chronic carriers? 5) The continued study of infections, including the carrier state, with a view to understanding the abnormalities created by the multiplying intracellular microbe and the means by which the cell corrects these and eliminates the intruder, should open new vistas in chemotherapy and immunology.