CARB-X funds development of novel antibiotic for MDR gonorrhea

CARB-X announced today that it is awarding $2.86 million to Microbiotix of Worcester, Massachusetts, to develop a new oral antibiotic for multidrug-resistant (MDR) gonorrhea.

The novel antibiotic, which is in the early stages of preclinical development, aims to combat the disease by targeting and inhibiting the trans-translation pathway of MDR Neisseria gonorrhoeae, which is essential for the bacterium to grow and replicate.

"Proposed as a single dose oral therapy, this innovative program has great potential, not only to address the urgent threat posed by MDR N. gonorrhoeae, but also to address other sexually-transmitted infection (STI) pathogens commonly found as coinfections," Microbiotix President and CEO Terry Bowlin, PhD, said in a press release from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator).

Drug-resistant gonorrhea has been labeled a priority pathogen by the World Health Organization and an urgent health threat by the US Centers for Disease Control and Prevention. An estimated 78 million people worldwide develop gonorrhea each year, and resistance to the last remaining antibiotics capable of treating the infection—ceftriaxone and azithromycin—is rising.

Microbiotix will be eligible for an additional $16 million in funding from CARB-X if the project meets certain development milestones. Since its launch in 2016, CARB-X has announced 59 awards totaling $198.5 million.
Mar 17 CARB-X press release

Antibiotic developer Tetraphase acquired by AcelRx

In another in a string of ominous signs for antibiotic development efforts, biopharmaceutical company Tetraphase Pharmaceuticals, maker of the novel tetracycline antibiotic eravacycline, announced yesterday that it has been acquired by AcelRx Pharmaceuticals.

The move comes less than 2 years after the Food and Drug Administration approved eravacycline (which is sold under the brand name Xerava) for the treatment of complicated intra-abdominal infections (cIAIs) caused by MDR pathogens. Tetraphase, of Watertown, Massachusetts, had received support from the Biomedical Advanced Research and Development Authority for development of the drug, which was seen as an important new weapon against antibiotic-resistant infections.

But, like other small companies in the antibiotic development space, Tetraphase has struggled financially. As drug-industry newsletter Endpoint News noted, Xerava generated only $3.6 million in sales in 2019, and Tetraphase's stock price tumbled from $61.40 on Aug 27, 2018—the date of FDA approval—to $1.45 on Mar 13.

Tetraphase and AcelRx, of Redwood City, California, said they were entering into a co-promotion agreement to market and promote Xerava for the treatment of cIAIs.

"We are excited to collaborate with AcelRx, a partner whose strategic goals complement our own," Tetraphase President and CEO Larry Edwards said in a company press release. "We continue to believe that Xerava is a key addition to the hospital anti-infective armamentarium, and believe that together with AcelRx we will be able to more effectively bring new treatments to patients in healthcare institutions."
Mar 16 Tetraphase press release
Mar 16 Endpoints News story

Australia releases new AMR strategy

The Australian government late last week released its national antimicrobial resistance (AMR) strategy for 2020 and beyond, calling for coordination across all sectors where antibiotics are used and close coordination with global efforts.

The 2020 strategy builds on the country's 2015 AMR response plan, which established the Antimicrobial Use and Resistance in Australia Surveillance System, created a One Health AMR online hub, and initiated surveillance projects in the animal sector. The new strategy will broaden those efforts to encompass AMR in food and the environment, and will include antifungal and antiviral resistance.

The government says the 2020 strategy will be underpinned by a series of national and sector-specific action plans outlining short- to medium-term goals. Among the key objectives are developing clear governance for AMR initiatives, preventing infections and the spread of resistance, establishing appropriate usage and stewardship practices, and creating a nationally coordinated surveillance system that covers all sectors.

"Across a number of sectors—locally, nationally and globally—efforts will be aligned and, through targeted collaboration, policy, practice and systems will be strengthened to minimise the development and spread of antimicrobial resistance," the report states. "Only such a holistic approach can ensure the continued availability of effective antimicrobials for decades to come."
Mar 13 Australia's 2020 and Beyond AMR strategy 

Study: Early antibiotics, nasal microbiota changes tied to asthma

A new study by US and Finnish researchers has found that receipt of antibiotics during infancy was associated with increased risk of developing childhood asthma, and that the antibiotics-asthma link was mediated in part by changes in nasal microbiota. The findings appeared in Clinical Infectious Diseases.

For the study, the researchers looked at a cohort of 923 children who were born in Finland from January 2008 to April 2010 and followed them from birth through 7.5 years of age. Specifically, they looked at antibiotic use through the first 11 months, longitudinal nasal microbiota profiles from 2 to 24 months, and development of asthma by age 7. The nasal microbiota profiles were assessed using 16S rRNA gene sequencing of nasal swabs collected from the children at 2, 13, and 24 months.

Using those data, the researchers then performed a causal mediation analysis to estimate the natural direct effect of systemic antibiotic treatments during age 0 to 11 months on the risk of developing asthma by age 7, and to what extent it was mediated by longitudinal changes in the nasal microbiota.

Of the 697 children included in the final analysis, 8.0% later developed asthma. Exposure to more than two antibiotic treatments by age 11 months was associated with a 4.0% increase in the absolute risk of developing asthma (total effect; 95% confidence interval [CI], 0.9% to 7.2%, P = 0.006), with a direct effect of a 3.3% increase (95% CI, 0.4% to 6.4%, P = 0.03).

Clustering of longitudinal nasal microbiota data identified six nasal microbiota profiles. Infants with more antibiotic treatments had a higher risk of having a profile with early Moraxella sparsity (per each antibiotic treatment, adjusted relative rate ratio, 1.38; 95% CI, 1.15-1.66; P < 0.001). Causal mediation analysis showed that this effect of antibiotics on asthma risk was mediated, in part, by longitudinal changes in the nasal microbiota (natural indirect effect, P = 0.008), accounting for 16% of the total effect.

"For clinicians, these findings lend additional support to the current guidelines that discourage unnecessary use of antibiotics, particularly in young children," the authors wrote. "Furthermore, our observations should not only facilitate further investigations into the complex interplay between antibiotic exposures, microbiota, and host response, but they also offer new avenues for prevention of childhood asthma."
Mar 14 Clin Infect Dis abstract