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Multi-resistant bacteria at large
In the U.S. alone, 1.7 million patients per year acquire an infection while in the hospital, resulting in 99 000 (5.8%) deaths (U.S. Centers for Disease Control and Prevention). During the past decade, the deaths from nosocomical infections have increased at an incredible annual rate of 20%, and the reason is the rapid development of antibiotic resistance by the causative bacteria.

Fortunately several new and effective antibiotics have been developed against multiresistant Gram-positive bacteria (e.g., MRSA strains of Staphylococcus aureus and VRE strains of Enterococcus faecalis. About half of the nosocomical infections are, however, caused by Gram-negative bacteria, and now multi-resistant extended-spectrum betalactamase (ESBL)-producing or even more resistant carbapenemase-producing strains of both Escherichia coli and Klebsiella pneumoniae, as well as the extremely resistant strains of Pseudomonas aeruginosa and Acinetobacter baumannii are appearing in many hospitals at double-digit rates.

While new arsenal against multiresistant Gram-negatives is desperately needed, the pipelines of pharma industry look thin. Gram-negatives are a much more difficult target than Gram-positives because they are protected by an additional outer layer (outer membrane) which is impermeable to most antibiotics that easily penetrate the cell wall of Gram-positive bacteria. In fact, more than 90% of the novel antibacterial agents of natural or synthetic origin have been found to be totally inactive against clinically important Gram-negatives.

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