Stewardship / Resistance Scan for Feb 18, 2020

CARB-X funds for peptides
Airborne antimicrobial resistance
Rising resistance in kids' pneumococci

CARB-X funs antibacterial peptide development

CARB-X said today it has awarded Lytica Therapeutics, of Cambridge, Massachusetts, up to $5.3 million to develop antibacterial peptides that have broad activity against multidrug-resistant bacteria for treating lung and other infections.  

In a news release, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) said Lytica could receive up to $11.6 million in additional funding if the project achieves certain development milestones, for a potential total of $16.9 million.

"There is an urgent need for innovative therapeutics and approaches to drug-resistant infections that, today, are killing some 700,000 people around the world each year," said Erin Duffy, PhD, chief of research and development at CARB-X. "The Lytica project is in the early phases of development, but if successful and ultimately approved for use in patients, it could represent tremendous improvement in the treatment of multidrug-resistant gram-negative pathogens."

Antimicrobial peptides are a family of peptides with therapeutic potential, but their clinical use is limited mostly to topical applications because of problems with toxicity, stability, and efficacy. Lytica's proprietary "stapling" technology aims to overcome these hurdles.

The company has produced compounds called stapled antimicrobial peptides that have demonstrated potent activity against multidrug-resistant bacteria, stability against degrading, and wide therapeutic potential. If successful, the project could produce treatments for a wide range of serious infections, including lung, urinary tract, and intra-abdominal infections.

Since its launch in 2016, CARB-X, a public-private partnership, has announced 57 awards exceeding $193 million, with additional funds possible if project milestones are met. Its goal is to invest $500 million by the end of 2021.
Feb 18 CARB-X news release


UK report examines airborne antimicrobial resistance

In a report today on airborne antimicrobial resistance, the UK Environment Agency says much more research is needed to determine how much of a health risk it poses.

The review and analysis of 88 relevant papers obtained from three academic databases found that, despite differences in study environments, methods used, and antibiotics studied, some basic conclusions emerged. Among those conclusions are that tetracycline resistance appears to be more prevalent in agriculturally associated air, industrial activities involving fecal matter (including farms) are associated with the highest levels of multidrug resistance reported to date, and the ubiquitous use of azole antifungals in medicine and agriculture—along with the ability of fungi to travel long distances in the air—makes airborne antifungal resistance a relevant threat.

Some of the questions that still need to be addressed, according to the report, are whether air is a primary route of antimicrobial resistance transmission to humans and other vulnerable hosts, and how the resulting risk compares with other transmission methods. The researchers say exploring the biophysics of airborne antimicrobial resistance could help answer some of these questions.

"More research is recommended to close knowledge gaps and test emergent hypotheses," the authors of the report write. "Also needed is a more concerted effort to report and share the results of antimicrobial susceptibility testing in a standardised way, and more careful and standardised collection and reporting of air sampling."
Feb 18 UK Environment Agency report


Study: In PCV-13 era, new strains of resistant pneumococci emerging

An analysis of Streptococcus pneumoniae isolates collected from young children in primary care settings has found reduced susceptibility to several antibiotic classes in the 13-valent pneumococcal conjugate vaccine (PCV-13) era, researchers report today in Clinical Infectious Diseases.

In the prospective cohort study, investigators from Rochester General Hospital Research Institute in Rochester, New York, collected nasopharyngeal and middle ear fluid samples from children ages 6 to 36 months during acute otitis media (ear infection) and routine healthy visits at primary care pediatric practices in Rochester from 2006 through 2016. They then performed antibiotic susceptibility testing on S pneumoniae isolates against a panel of 16 antibiotics from 10 classes. All children were up to date on vaccines, receiving the PCV-7 vaccine from 2006 until April 2010 and PCV-13 after April 2010.

From 2006 through 2016, 1,201 S pneumoniae isolates were characterized from 1,072 visits of 448 children. Analysis of susceptibility trends showed that, after introduction of PCV-13, susceptibility to S pneumoniae to antibiotics, especially penicillin, initially improved, largely because of the disappearance of serotype 19A, which is included in PCV-13. But beginning in 2013, antibiotic susceptibility among S pneumoniae strains began decreasing with the emergence of three serotypes (11A, 35B, and 35F) not included in PCV-13. In addition to reduced susceptibility to penicillin, the most recent isolates also showed reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems.

The authors of the study say the reduced susceptibility to third-generation cephalosporins, fluoroquinolones, and carbapenems could have implications for future treatment of invasive pneumococcal disease. They also note that neither of the two PCVs in advanced development (PCV-15 and PCV-20) includes serotypes 35B or 35F.
Feb 18 Clin Infect Dis abstract

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