immune suppressive therapies in transplant patients, aggressive chemotherapeutic practices in oncology, and most recently the use of TNF-␣ antagonists in treating rheumatoid arthritis. Ironically, even improved therapies for other diseases are contributing to an increase in infectious diseases, e.g. In sum, bacterial diseases in general, and antibiotic-resistant bacterial infections specifically, are increasing in both developing and developed countries. In developing countries periodic malnutrition, poor sanitation, the spread of HIV infection, and, almost paradoxically, increasing population density, coupled with the ready availability of cheap, generic antibacterials (often of poor quality), are leading to a mushrooming of resistant bacterial strains.
This has produced a population that is becoming increasingly immunosuppressed.
Part and parcel of the resistance problem are dramatically changing demographics iiiĬonsisting of an aging population with a decline in the robust response to infections. There is less argument on the need for new antibacterial agents and therapeutic strategies to avoid the emergence and dissemination of resistant bacteria. No other area of therapeutic focus can boast this level of commercial, not to mention therapeutic success. Not only are infectious disease therapeutics the second largest source of revenue for pharmaceutical companies (behind cardiovascular drugs), with antibacterial drugs taking the lion’s share, but there are also no fewer than six branded products garnering over $1 billion annually, despite fierce generic competition. The use of this pharmaceutical industry calculus has long been the rationale used for the chronic underresourcing of antibacterial research programs (not to mention anemic public funding for the study of pathogenic bacteria and antibacterial drug resistance) but this actually flies in the face of commercial and public health realities. It has been reasoned that it makes more commercial sense to treat chronic conditions requiring years of therapy rather than curing diseases with short courses of treatment. After all, even the most stubborn of bacterial infections rarely, if ever, require more than six months of treatment, and the average course of therapy is under seven days. This well-noted futility has led some to suggest that this approach will never prove productive, that the majority of “novel” targets are not “druggable,” and that industry research dollars are better spent elsewhere. To date no antibacterial compounds identified by target based screening have advanced into clinical testing much less been used clinically to treat bacterial infections.
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