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Multiresistant Gram-negative infections are an increasing problem in hospitals and healthcare facilities worldwide. While much attention has been paid to Gram-positive pathogens such as methicillin-resistant Staphylococcus aureus and vancomycin-resistant Enterococcus lately, the importance of Gram-negative nosocomial infections has also been recognized globally.Recent reports have described the spread of carbapenemase-producing Klebsiella pneumoniae across North America. In addition, many strains of Pseudomonas and Acinetobacter in Asia are resistant to all known antibiotics. The global epidemiology of multiresistant Gram-negative pathogens seems to vary by continent. There are very few existing agents which can be used for these pathogens and there are limited options on the horizon. This limited therapeutic armamentarium has been an impetus for novel approaches including combination therapies and increased attention to infection control and prevention efforts.Clinicians need to be aware of the rising problem of resistance in nosocomial and community-acquired Gram-negative pathogens. Novel agents are urgently needed to combat these infections and innovative infection control strategies need to be devised to protect our vulnerable patients.