BARDA provides $32 million for new C difficile drug candidate
The Biomedical Advanced Research and Development Authority (BARDA) has awarded drug maker Summit Therapeutics $32 million over the next 2 years for development of a new antibiotic for Clostridium difficile infection (CDI).
The money will enable UK-based Summit to conduct phase 3 clinical trials of Ridinilazole, an orally administered small-molecule antibiotic that specifically targets C difficile bacteria while leaving beneficial gut bacteria alone, according to a news release yesterday from the Department of Health and Human Services (HHS), BARDA's parent agency. A phase 2 proof-of-concept clinical trial showed that the drug was highly preserving of the microbiome of patients compared the standard of care, vancomycin, and substantially reduced rates of recurrent C difficile.
CDI occurs in patients as a result of prolonged use of wide-spectrum antibiotics, which kill the body's beneficial gastrointestinal flora and allow C difficile bacteria to flourish. Treatment with wide-spectrum antibiotics further disrupts the gut microbiome, which can lead to recurrence. Recurrent CDI occurs in 20% to 30% of patients, with increasing rates of recurrence with each subsequent episode. The Centers for Disease Control and Prevention estimates that C difficile causes nearly half a million infections and 15,000 deaths each year.
Ridinilazole has received Qualified Infectious Disease Product designation from the Food and Drug Administration (FDA), which puts the drug on a fast track for FDA review.
BARDA, an agency within the HHS Office of the Assistant Secretary for Preparedness and Response, is funding the development of Ridinilazole as part of its efforts to develop drugs that treat biothreats such as anthrax and tularemia. Anthrax and tularemia infections require 60 or more days of antibiotic treatment, which can put patients at risk for CDI.
"To save lives from biothreats, whether it's anthrax or tularemia, doctors must be able to treat not just the biothreat itself but also opportunistic secondary infections that may occur,” BARDA director Rick Bright, PhD, said in the HHS release. "Partnering to develop drugs that treat biothreats as well as common, serious infections has proven to be an innovative, sustainable business model for industry and the federal government."
Sep 11 HHS press release
Sep 11 Summit Therapeutics press release
High levels of antimicrobial resistance, dearth of data found in Africa
A systematic review of studies on antimicrobial resistance (AMR) in Africa has found high levels of resistance to commonly prescribed antibiotics. Of greater concern, however, is a lack of recent AMR data for more than 40% of the continent, a finding that highlights the significant knowledge gaps hindering efforts to fully understand the global magnitude of the problem.
The review, published yesterday in BMC Infectious Diseases, identified 144 studies on AMR prevalence and surveillance in Africa published from 2013 through 2016; the selected studies analyzed samples from a total of 149,733 patients. The highest percentage of studies (40.9%) were from countries in East Africa, and the fewest studies (4.2%) were from countries in the South African region. No studies were identified in 23 of 54 (42.6%) countries.
In the 144 studies analyzed, 13 gram-negative and 5 gram-positive bacteria were tested against 37 different antibiotics. Overall resistance to commonly used drugs like amoxicillin (median resistance [MR], 72.9%) and trimethoprim/sulfamethoxazole (MR, 75%), the first-line drugs for urinary tract infections, was high. MR of Escherichia coli, the most common gram-negative bacterium reported, to amoxicillin and trimethoprim was 88.1% and 80.7%, respectively. Among gram-positive bacteria, penicillin resistance in Streptococcus pneumoniae was reported in 14 of 144 studies, with an MR of 26.7%.
Among other significant findings, ciprofloxacin resistance in Salmonella Typhi was rare, and no documented ceftriaxone resistance was reported in Neisseria gonorrhea. Ampicillin resistance in Haemophilus influenzae was high (MR, 100%). Carbapenem resistance was common in Acinetobacter spp and Pseudomonas aeruginosa but uncommon in Enterobacteriaceae. Vancomycin showed the lowest resistance pattern for all tested gram-positive bacteria.
The authors of the study highlight the overall lack of AMR data and note that the lack of consistency in measurement and reporting of susceptibility data makes it difficult to compare findings among different countries. They suggest that standardizing AMR methods and interpretation guidelines "could allow for better comparability of results and improved resistance tracking."
Sep 11 BMC Infect Dis study