Gram-negative Bacterial Infections

Gram-negative pathogens are responsible for half of all healthcare associated infections (HAIs). The CDC estimates that there were 1.7 million HAIs in the U.S. and the estimated number of death associated with HAIs were 99,000, costing the U.S. health care system $20B per year. Gram-negative pathogens are the primary cause of hospital-acquired infections in the ICU. While mortality due to these infections is already high, infections caused by MDR strains result in significantly higher mortality and hospital length of stay when compared to those caused by susceptible strains.

While new antibiotics introduced over the past 15 years have made significant progress in the fight against resistant Gram-positive bacteria, including MRSA, a recent CDC report highlighted the urgent need for novel antibacterials that are effective against Gram-negative bacteria, particularly carbapenem-resistant Enterobacteriaceae (CRE), MDR-Acinetobacter baumannii and Pseudomonas aeruginosa. Several recently approved or late-stage antibacterials provide adequate coverage of less resistant forms of CRE and P. aeruginosa, but significant spectrum gaps remain.

Immunocompromised patients are at significantly higher risk of developing a MDR Gram-negative infection and have inadequate immune systems to adequately fight the infections. Novel agents are needed that provide both an antibacterial effect in addition to leveraging the remaining immune system to help clear the infection. New resistance mechanisms, such as the emergence of the mcr-1 resistance gene have rendered even toxic last line agents ineffective.

Mortality Rate by Susceptibility of Pathogen

Mortality rates are much higher in patients with resistant bacteria compared to susceptible strains.