Abstract
The development of nontoxic broad-spectrum antimicrobial drugs in the mid-20th century led to a culture of empiricism, underdevelopment of diagnostics, neglect of immunotherapy, and selection for drug resistance, which together created the conditions that underlie the current crisis. In 1996 an article in this journal predicted a crisis in infectious diseases, which subsequently unfolded with a paucity of new drugs, increases in antimicrobial resistance, and underdevelopment in both immunotherapy and diagnostics. This article argues that the root cause of the current-day problems lies in the enormous success of the mid-20th century antibiotic revolution. The availability of low-toxicity broad-spectrum drugs fostered a culture of empiricism and widespread use, which in turn stunted the development of both the specialty and rapid diagnostics while promoting increases in resistance. Two decades later, there are promising signs that widespread recognition of these problems is leading to fundamental changes in the approach to the therapy of infectious diseases. Ultimately, a concerted effort to simultaneously develop pathogen-specific drugs, immunotherapy, and improved diagnostics could provide a qualitatively new platform for confronting the challenge of infectious diseases, which now also includes host dysbiosis.