New approaches for treatment of Infectious Diseases
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 postantibiotic 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. Indeed, the past success of antibiotics may be judged by the degree to which we have taken them for granted. As conventional antibiotics become less reliable, alternate strategies are receiving more attention. Here, we provide an overview of several “nonantibiotic” approaches that are being investigated for the treatment and prevention of bacterial infections. Vaccine development and modulation of host immunity have been covered in a recent review and will not be discussed here.
Successful bacterial pathogens produce virulence factors, molecules that allow them to resist clearance by the host, to invade and gain access to deeper tissues, and to damage host cells. A substantial amount of effort has been devoted to developing agents that block the activities of virulence factors and hence halt pathogenesis until the host immune response or adjunctive antibiotics kill the bacteria.
Targeting Toxins and Secretion Systems
Secreted toxins play a major role in the pathogenesis of many medically important bacteria, and several of these have been targeted with the aim of blocking infection (Table. 1). (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.) Agents developed to inhibit toxins predominantly fall into 1 of 2 categories: chemical inhibitors and antibodies.
The extraordinary success of conventional antibiotics led to a focus on development of these agents to the exclusion of other antibacterial strategies. A silver lining in the current dark cloud of antibiotic resistance is that these alternative strategies are again being pursued, although significant challenges remain before they can be widely adopted into clinical practice. First, since many of these approaches are species or even strain specific rather than broad spectrum, rapid diagnostic technologies will be necessary to identify candidate patients in a timely manner. Second, the narrow spectrum of many of these compounds and the corresponding smaller sales markets make them less attractive for development by pharmaceutical companies.
Journal of Infectious Diseases and Diagnosis