Bad Bugs, No Drugs: No ESKAPE! An Update from the Infectious Diseases Society of America

Abstract

The Infectious Diseases Society of America (IDSA) continues to view with concern the lean pipeline for novel therapeutics to treat drug-resistant infections, especially those caused by gram-negative pathogens. Infections now occur that are resistant to all current antibacterial options. Although the IDSA is encouraged by the prospect of success for some agents currently in preclinical development, there is an urgent, immediate need for new agents with activity against these panresistant organisms. There is no evidence that this need will be met in the foreseeable future. Furthermore, we remain concerned that the infrastructure for discovering and developing new antibacterials continues to stagnate, thereby risking the future pipeline of antibacterial drugs. The IDSA proposed solutions in its 2004 policy report, "Bad Bugs, No Drugs: As Antibiotic R&D Stagnates, a Public Health Crisis Brews," and recently issued a "Call to Action" to provide an update on the scope of the problem and the proposed solutions. A primary objective of these periodic reports is to encourage a community and legislative response to establish greater financial parity between the antimicrobial development and the development of other drugs. Although recent actions of the Food and Drug Administration and the 110th US Congress present a glimmer of hope, significant uncertainly remains. Now, more than ever, it is essential to create a robust and sustainable antibacterial research and development infrastructure--one that can respond to current antibacterial resistance now and anticipate evolving resistance. This challenge requires that industry, academia, the National Institutes of Health, the Food and Drug Administration, the Centers for Disease Control and Prevention, the US Department of Defense, and the new Biomedical Advanced Research and Development Authority at the Department of Health and Human Services work productively together. This report provides an update on potentially effective antibacterial drugs in the late-stage development pipeline, in the hope of encouraging such collaborative action.

Plasticity, dynamics, and inhibition of emerging tetracycline resistance enzymes

“…This indicates that tetracycline-inactivating enzymes pose a threat for facile acquisition by additional human pathogens. Indeed, we show that tet (56) is present and functional in the human pathogen L. longbeachae , and tet (X) has now been reported in four out of six ESKAPE pathogens 46-48 , demonstrating the urgency of this threat. Our results reveal the structural basis for plasticity and dynamics in substrate binding in these enzymes.…”

“…Growing evidence, however, indicates that enzymatic tetracycline inactivation is a widespread feature in soil microbial communities 28 , and is a recently observed emerging threat in human pathogens 46-48 . Flavoenzymes display a proclivity for horizontal gene transfer and gene duplication, bestowing the potential to spread between bacteria and acquire novel functions 49 .…”

Molecular profiling and antimicrobial potential of endophyticGliomastix polychromaCLB32 inhabitingCombretum latifoliumBlume

“…Emergence of multidrug-resistant (MDR) microorganism infections has generated considerable attention in recent decades (Boucher et al 2008; Cars et al 2008). Antibiotic resistance is one of the greatest challenges facing modern medicine (Spellberg et al 2008).…”

The short‐chain oxidoreductase Q9HYA2 from Pseudomonas aeruginosa PAO1 contains an atypical catalytic center

“…It is the top cause of nosocomial pneumonial infections with a mortality rate of up to 60% associated with multidrug resistant strains. 4,5 Although the substrate of this enzyme is unknown, the atypical catalytic site is found in a total of 28 probable SCOR proteins, each from a different species. All of these orthologs exhibit the other classic SCOR motifs and tend to be present within an operon conserved across these species.…”