Our discovery program focused on identifying antibiotics that will be effective against the toughest Gram-negative multidrug-resistant bacteria. This focus is helping to address the lack of new antibiotics to fight antibiotic-resistant bacteria recently identified as priority pathogens by the Centers for Disease Control and Prevention and the World Health Organization. In addition, we explored potential uses for our technology outside antibacterial indications.
Antibiotic Resistance Is a Global Public Health Crisis
As the result of widespread antibiotic use, many strains of bacteria have become resistant to formerly effective antibiotics, limiting therapeutic options for patients. The resistance problem has been recognized as an urgent threat by the World Health Organization, the Centers for Disease Control and Prevention, and the Infectious Diseases Society of America. Of most concern are patients with bacterial infections that are resistant to multiple classes of antibiotics, referred to as multidrug-resistant (MDR), pandrug-resistant (PDR), or extensively drug-resistant (XDR) bacterial infections.
Types of Bacteria and the Infections They Cause
Bacteria can be broadly differentiated by the structure of their bacterial cell walls and comprise two primary categories: Gram-negative and Gram-positive.
- Gram-negative bacteria that have developed resistance to existing drugs include: Escherichia coli that causes urinary tract, intra-abdominal, skin, and bloodstream infections; Salmonella and E coli that cause foodborne infections; and Acinetobacter baumannii, Pseudomonas aeruginosa, and Klebsiella pneumoniae species, which are responsible for serious infections, such as pneumonia, seen in patients in healthcare settings
- Gram-positive bacteria that have developed resistance to existing drugs include Streptococcus pneumoniae that causes pneumonia, ear infections, bloodstream infections, and meningitis; Staphylococcus aureus that causes skin, bone, lung, and bloodstream infections; and Enterococcus that can be involved in abdominal and urinary tract infections
Targeting Gram-Negative Bacteria Is a High Priority
While new antibiotics introduced over the past 10 to 15 years have made progress in the fight against resistant Gram-positive bacteria (such as methicillin-resistant S aureus), a September 2013 Centers for Disease Control and Prevention report highlighted the need for novel antibiotics effective against resistant Gram-negative bacteria. Carbapenem-resistant Enterobacteriaceae (CRE), which include MDR strains of E coli and K pneumoniae, represent the most urgent resistance threat. Other Gram-negative bacteria classified as serious resistance threats include extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, A baumannii, and MDR P aeruginosa.
Gram-negative bacteria, both susceptible and resistant strains, are the primary causes of serious infections that require treatment in the hospital. According to data from the U.S. National Healthcare Safety Network, these bacteria are now estimated to account for more than 30% of all hospital-acquired infections. While mortality due to these infections is already high, infections caused by resistant strains result in significantly higher mortality and hospital length of stay when compared with those caused by susceptible strains.
Global Coordinated Efforts Are Needed to Combat Antibiotic Resistance
The issue of antibiotic-resistant bacterial infections is growing at an alarming rate. Global health organizations, government and regulatory agencies, academic institutions, and biopharmaceutical companies are focused on combating this problem through initiatives that support antimicrobial stewardship, infection control, surveillance monitoring, and development of rapid diagnostics and novel antibiotic treatments. Tetraphase is committed to supporting these efforts as it strives to deliver innovative and accessible treatments to address this public health crisis.
Other Therapeutic Areas
A number of potential tetracycline uses in nonantibiotic therapeutic areas, including oncology and inflammatory diseases, have been reported in the scientific literature. Until now, these opportunities could not be fully explored because of limited synthetic access and availability of compounds. With our tetracycline chemistry expertise and extensive tetracycline library, Tetraphase was uniquely suited to investigate serious conditions beyond bacterial infections. Please note, these indications are not currently approved by the FDA, and Tetraphase does not promote use of products outside their approved labels.