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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 Affiliation: Arturo Casadevall, Albert Einstein College of Medicine, Division of Infectious Diseases of the Department of Medicine, Department of Microbiology and Immunology, 1300 Morris Park Avenue, Bronx, NY 10461, USATel: 1 7; Fax: 1 7 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.Like therapy for infectious diseases, the treatment of tumors has relieved  heavily on antibiotics made by microorganisms; adryamicin, actinomycin D, bleomycin etc. Like antimicrobial antibiotics, these antimetabolite antibiotics are each nonspecific in the sense that they are cytotoxic to multiple tumors.However, unlike most antimicrobial antibiotics, these agents have tremendous toxicity for the host and, consequently, are never used empirically.Albert Einstein College of Medicine 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.For some diseases such as meningococcal meningitis, small-molecule antimicrobial therapy was clearly more effective than serum therapy; however, for pneumococcal pneumonia the difference in efficacy was less clear.In addition to serum therapy, the few other therapies available (e.g., quinine for malaria, salvarsan for syphilis, optochin for pneumococcus, and phage therapy) were all pathogen specific.
In comparing the ages of antimicrobial therapy, it is clear that the change in the specificity of therapeutic agents did not affect all types of antimicrobial therapy equally.
In this essay, I argue that this change was to have enormous implications, which are root causes for some of the problems we face today.
In evaluating the therapeutic paradigm for microbial diseases, it is worthwhile contrasting it with the therapy of cancer.
Serum therapy for viral diseases was specific and current antiviral drugs remain largely pathogen-specific, with the caveat that some drugs like acyclovir have activity against multiple herperviruses [ diseases, there was no effective therapy in the preantibiotic era and most drugs that were subsequently developed (isoniazid, ethambutol, and others) were used primarily for the therapy of tuberculosis.
For fungal diseases, there was no effective therapy prior to the late 1950s when amphotericin B was introduced; a compound active against most fungal pathogens and antifungal therapy has always relied on nonpathogen-specific agents.
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Hence, oncology practice has placed great emphasis on diagnosis and in exploiting subtle pharmacological differences between these agents to enhance their therapeutic index.