The case for pathogen-specific therapy.

At the beginning of the twenty-first century, the treatment of microbial diseases is increasingly complicated by drug resistance, the emergence of new pathogenic microbes, the relatively inefficacy of antimicrobial therapy in immunocompromised hosts, and the reemergence of older diseases, often with drug-resistant microbes. Some of these problems can be traced to the switch between pathogen-specific antibacterial therapy and the nonspecific antibacterial therapy that followed the transition from serum therapy to modern antimicrobial chemotherapy. The widespread availability of cheap, effective, nontoxic wide-spectrum antibacterial therapy for almost 75 years fostered a culture of therapeutic empiricism that neglected diagnostic technologies. Despite unquestioned lifesaving efficacy for individuals with microbial diseases, the use of broad-spectrum antimicrobials was associated with fungal superinfections and antibiotic-associated colitis, helped to catalyze the emergence of resistance, and is now tentatively associated in the pathogenesis of certain chronic diseases, including atopy, asthma and - perhaps - certain forms of cancer. This article briefly reviews these trends and suggests that the current strategy of nonspecific therapy is fundamentally unsound because it damages the microflora and - consequently - the human symbiont. The essay argues for the development of immunotherapy and pathogen-specific therapies, especially with regard to bacterial and fungal diseases, and suggests possible routes to that future.