Wildcatters welcome: the need for new antimicrobial agents

In a 1969 address to the US Congress, the Surgeon General suggested that it was time to close the book on infectious diseases [1]. Twenty years of successes associated with clinical use of penicillin and other antimicrobial agents had buoyed the hopes of clinicians and the public alike. Moreover, the pharmaceutical industry was on the verge of a dramatic expansion in developing new antimicrobial agents that would offer broader coverage, improved safety and more convenient dosing regimens. The success of the smallpox and polio vaccines suggested that major viral illnesses would be controlled and yeasts and molds had not yet become common causes of serious disease. The Surgeon General may have closed the book that was before him but we have come to realize over the subsequent 4 decades that this book represented merely the first volume in a long-running saga. The introduction of vancomycin, methicillin and the cephalosporins to treat emerging penicillin-resistant staphylococci was rapidly followed by the appearance of resistant Gram-positive species, such as methicillinresistant staphylococci, vancomycin-resistant enterococci and more recently, vancomycinresistant Staphylococcus aureus. On the Gramnegative side, the use of ampicillin and cephalosporins was followed by the surfacing of resistance in normally susceptible species such as Escherichia coli and Klebsiella pneumoniae, in addition to the emergence as important pathogens of intrinsically resistance species, such as Pseudomonas aeruginosa and Acinetobacter baumanni. These and several other pathogens found comfortable homes in the antibiotic rich, immunity poor patients inhabiting the modern hospital, as did many species of yeasts and molds. While it is still quite rare to encounter bacteria resistant to all clinically available antimicrobial