The rapid emergence of drug-resistant bacteria poses a serious threat to world health and underscores the importance of developing new antibiotics. A particularly threatening group of pathogens causing serious hospital infections has been coined “ESKAPE” (Enterococcus faecium, Staphylococcus aureus, Klebsiella pneumoniae, Acinetobacter baumanii, Pseudomonas aeruginosa, and Enterobacter species) as they are able to “escape” the effects of antibacterial drugs. Mortality rates from resistant bacterial infections are reported to be as high as 25 000 deaths in Europe each year. Among the ESKAPE pathogens, methicillin-resistant S. aureus (MRSA) and vancomycin-resistant enterococci (VRE) have emerged as two of the most troubling owing to the staggering cost of hospital care and limited treatment options for individuals infected with these organisms. At present >80% of E. faecium isolates from hospital-associated infections in the United States are resistant to vancomycin.
Another rapidly growing threat is posed by multi-drug resistant Gram-negative pathogens. Increasingly, ß-lactamase driven resistance mechanisms are rendering clinically important ß-lactam antibiotics, including carbapenems, inactive. Notably, such resistance mechanisms are rapidly spread through horizontal gene transfer between different species of bacteria. Clearly, new antibiotics that operate via novel modes of action are urgently needed to counter the growing problem of drug-resistant bacteria.