Abstract
Bacterial resistance to the currently available antibiotics is a worldwide problem with catastrophic potential (Kunin, 1993; Berkowitz, 1995; Domagala and Sanchez, 1997). In the US, overall mortality from infectious diseases has increased 58% with deaths from respiratory infections and septicemia up 20 and 83% respectively (Pinner et al., 1996). Increased resistance has been documented for every major group of pathogens with methicillin resistant Staphyloccus aureus (MRSA), vancomycin resistant enterococci (VRE) and β-lactam resistant streptococci causing the greatest alarm (Cormican and Jones, 1996; Howe et al., 1996). In fact, VRE has been described as the most feared nosocomial pathogen today (Hagman and Strausbaugh, 1996). The fear of vancomycin resistant MRS A has sparked calls for stringent preemptive controls (Edmund et al., 1996). Equally alarming is the dramatic increase in resistance among the gram negative organisms (Jones, 1996). Nosocomial pneumonias (often with resistant organisms) occur in 0.5–5% of all hospitalized patients with a mortality of 20–70%, and an added annual cost of $2.5 billion for increased care and treatment (Gaynes and Lynch, 1991; Swartz, 1994). So great and urgent is the problem that the prestigious journal Science has devoted two issues to bacterial resistance (Travis, 1994; Koshland, 1992), and the American Society for Microbiology formed a Task Force to define the problem and make recommendations. Their insightful report, issued in 1995 (Report 1995), called for an increased effort in the discovery of new drugs and new drug targets in bacteria.
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Domagala, J.M. et al. (1998). Bacterial Two-Component Signalling as a Therapeutic Target in Drug Design. In: Rosen, B.P., Mobashery, S. (eds) Resolving the Antibiotic Paradox. Advances in Experimental Medicine and Biology, vol 456. Springer, Boston, MA. https://doi.org/10.1007/978-1-4615-4897-3_14
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