Stewardship / Resistance Scan for Jan 03, 2019

Novartis shares antibiotic data
New CARB-X funding
MCR-1 genes in food
Risk factors for resistant UTIs

Novartis shares data from discontinued antibiotics program

The Pew Charitable Trusts announced today that Novartis has shared data from its discontinued antibiotics development program on Pew's open-access database, known as SPARK (Shared Platform for Antibiotic Research and Knowledge).

According to a Pew news release, Novartis shared data from its LpxA, LpxK, and LpxD antibacterial programs, which explore new ways to attack gram-negative bacteria. The company is no longer pursuing development of these molecules after announcing in July that it was ending its antibacterial and antiviral research programs.

SPARK is a cloud-based platform that's open to scientists from industry, academia, government, and nonprofit research groups who are working on antibiotic development. Launched by Pew in September, its aim is to help spur basic research into new antibiotics for gram-negative bacterial pathogens by providing scientists access to chemical and biological data from previously published and unpublished studies. SPARK's specific focus is on molecules that take new approaches to overcoming the defenses of gram-negative bacteria.

The move is significant because pharmaceutical company data on discontinued antibiotic development programs would normally remain with the companies. But in October, drug maker Achaogen became the first pharmaceutical company to release data from a discontinued antibiotic development program to SPARK.

Lynn Silver, an independent consultant in antibacterial discovery who's been working with Pew to update the SPARK database, said she hopes other pharmaceutical companies will follow suit. "The reality is that bacteria are developing resistance faster than we're finding new drugs to defeat them," Silver said in the news release. "In order to change that, we must salvage and make the most of every bit of data out there—published or unpublished."
Jan 3 Pew news release
Oct 22, 2018, CIDRAP News story "Achaogen to share data from discontinued antibiotic program"


CARB-X to fund new antibiotic for multidrug-resistant lung infections

CARB-X announced today that it's awarding up to $5.7 million in funding to San Diego–based biotechnology company Forge Therapeutics to develop an antibiotic for lung infections caused by Pseudomonas aeruginosa and other multidrug-resistant gram-negative bacteria.

The money will enable the company to evaluate and further develop a class of novel, non-hydroxamate LpxC inhibitors, which target an enzyme that helps construct the tough outer membrane of gram-negative bacteria. Several companies have worked on drugs targeting LpxC, but to date no effective compounds have been developed. Forge's LpxC inhibitors have demonstrated safety and the ability to kill gram-negative superbugs in animals.

The award is the second that Forge has received from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), a public-private partnership that provides non-dilutive funding to companies in the pre-clinical stages of developing new antibiotics, diagnostics, and other therapeutics for the most critical antibiotic-resistant pathogens. Since 2016, CARB-X has awarded over $97.7 million to more than 30 projects.

"We are gratified to receive this opportunity to expand our collaboration with CARB-X," Forge CEO Zachary Zimmerman, PhD, said in a CARB-X news release. The company could receive an additional $5.4 million if it reaches certain project milestones.
Jan 3 CARB-X news release


Seven MCR-1 isolates identified in food samples in China

Scientists have identified seven colistin-resistance MCR-1–containing isolates from food samples collected from 2012 to 2016 in China, according to a letter yesterday in the Journal of Antimicrobial Chemotherapy.

The researchers analyzed 2,555 Salmonella isolates cultured from foods in the study period, varying from 174 to 1,100 samples in a given year. Using quantitative polymerase chain reaction, they identified seven MCR-1 genes, which convey resistance to colistin, a "last resort" antibiotic for multidrug-resistant organisms. The gene was first identified in 2015 in China and has since been detected in more than 30 countries.

Three MCR-1–positive isolates were from pork samples; 2 from dumplings, 1 of which contained pork; and 1 each from an egg and a whole chicken. The samples were from five provinces. Four isolates were Salmonella Typhimurium, with the others being Indiana, London, and Derby. The authors say this predilection for the Typhimurium strain is consistent with previously reported data.

The authors conclude, "There is a trend for Salmonella spp. becoming a reservoir for the mcr-1 gene. . . . Deep-level genomic characterization is required to understand fully the mechanism of the colistin resistance and its transmission."
Jan 2 J Antimicrob Chemother letter


Study identifies risk factors for community-acquired, ESBL UTIs

A case-control study today in Open Forum Infectious Diseases has found that patients in the community who have indwelling urinary catheters, a history of recurrent urinary tract infections (UTIs), or recent antimicrobial use are at heightened risk for UTIs caused by extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae.

In the study, researchers from the University of Utah and Intermountain Healthcare identified 251 patients admitted to Intermountain's 22-hospital system with an ESBL UTI from 2001 through 2016 and matched them 1:1 with patients who had UTIs caused by non-ESBL Enterobacteriaceae. They were looking to determine risk factors for community-acquired ESBL UTIs, which have been rising in recent years. ESBL infections can be difficult to treat and are associated with longer hospital stays and higher morbidity and mortality.

In a univariate analysis, the researchers found that a history of repeated UTIs, neurogenic bladder, urinary catheter presence at admission, and previous exposure to third-generation cephalosporins or fluoroquinolones within 3 months were associated with a higher risk of ESBL UTIs. After controlling for severity of illness and comorbid conditions during the multivariate analysis, history of repeated UTIs (adjusted odds ratio [aOR], 6.40; 95% confidence interval [CI], 3.42 to 12.66, P < 0.001), presence of urinary catheter at admission (aOR, 2.36; 95% CI, 1.15 to 4.98, P < 0.05), and prior antibiotic exposure (aOR, 7.98; 95% CI, 2.92 to 28.19, P < 0.001) remained associated with heightened risk.

The authors note that patients with ESBL and non-ESBL UTIs often have similar symptoms, which makes decisions about empiric antibiotic therapy more difficult. They say the findings could help clinicians initiate effective antibiotic therapy earlier and improve clinical outcomes. 
Jan 3 Open Forum Infect Dis abstract

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