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Clin Infect Dis. 2016 Jul 1; 63(1): 89–95. Published online 2016 Mar 29. doi: 10.1093/cid/ciw200  PMCID: PMC4901866  PMID: 27025826  Beyond Antibiotics: New Therapeutic Approaches for Bacterial Infections Alan R. Hauser,1 Joan Mecsas,2 and Donald T. Moir3

The problem of antibiotic resistance in bacteria has reached the crisis stage. Coincident with ever-increasing rates of resistance to conventional antibiotics is the slowing in development of novel-acting antibiotics by the pharmaceutical industry.

The convergence of these trends has led to the relatively common occurrence of multidrug- and extensively drug-resistant bacteria.

The World Health Organization recently reported that “a post-antibiotic era—in which common infections and minor injuries can kill—far from being an apocalyptic fantasy, is instead a very real possibility for the 21st century”.

To fathom such a future, one need only ponder the past. At the beginning of the 20th century, mortality rates were 100% for endocarditis, >95% for meningitis, 30% for pneumonia, and 10% for serious skin infections.

·       Secreted toxins play a major role in the pathogenesis of many medically important bacteria. ….Here, we will use the term “toxin” to refer to factors secreted by bacteria that promote infection, including both traditional toxins and effector proteins directly injected into host cells by specialized secretion systems.

·       Biofilms growing on inert surfaces, such as catheters or prosthetic joints, and biofilms growing on body structures, such as heart valves and teeth, are major sources of infections. Their eradication can be difficult in part because bacteria growing in biofilms are in a physiological state that allows them to persist in the presence of antibiotics that typically kill planktonic-growing bacteria. In addition, the extracellular matrix of the biofilm itself can prevent antibiotic penetration into the biofilm