Stewardship / Resistance Scan for Jun 30, 2020

Funds for CRISPR-based phage treatment
;
Antimicrobial stewardship in Saudi hospitals
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Impact of rapid ID, susceptibility test

CARB-X to fund its first CRISPR-based phage project

CARB-X announced an award today of up to $1.82 million to French biotechnology company Eligo Bioscience to develop CRISPR- and bacteriophage-based therapeutics to prevent multidrug-resistant infections in transplant patients.

Eligo's EB004 project takes bacteriophages, which are viruses that selectively infect and kill bacteria, and designs them to inject synthetic DNA into targeted bacterial populations—extended-spectrum beta-lactamase-producing and carbapenem-resistant Escherichia coli and Klebsiella pneumoniae—in a patient's digestive tract. The DNA is designed to circumvent bacterial defense systems and enable the expression of a CRISPR-Cas system that creates double strand DNA breaks only in the antibiotic resistance genes carried by the targeted bacteria, selectively killing the bacteria carrying these genes and leaving those that don't carry antibiotic-resistance genes alone.

The idea behind the project is to eliminate these multidrug-resistant pathogens from a transplant patient's microbiome before the procedure to prevent the onset of life-threatening post-operative infections, without disrupting any beneficial bacteria.

"Eligo is developing a new class of targeted biotherapeutics to selectively eliminate certain multidrug-resistant bacteria by combining the specificity of CRISPR and the ability of bacteriophages to deliver DNA into bacteria," CARB-X chief of research and development Erin Duffy, PhD, said in a press release. "This innovative approach, if successful, offers additional benefits in that it can prevent multi-drug-resistant infections while not harming bacteria in the microbiome."

This is the first CRISPR-based phage project funded by CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator). Eligo could receive up to $7.05 million in funding if certain project milestones are met.
Jun 30 CARB-X press release

 

Antimicrobial stewardship helps Saudi hospitals cut antibiotic use, expenses

Implementation of antimicrobial stewardship programs at four private hospitals in Saudi Arabia resulted in reduced antibiotic use and expenditures and lowered incidence of healthcare-associated infections, Saudi researchers reported yesterday in Antimicrobial Resistance and Infection Control.

In a pre-post quasi-experimental study, the researchers aimed to measure the impact of the antibiotic stewardship program implemented at four Al Habib Medical Group hospitals by comparing the 1-year baseline period prior to implementation (2015) with 4 years of post-implementation data (2016 through 2019). Patients were included on the pre- and post-implementation arms if they were on any of 10 selected broad-spectrum antibiotics (imipenem/cilastatin, piperacillin/tazobactam, colistin, tigecycline, cefepime, meropenem, ciprofloxacin, moxifloxacin, teicoplanin, and linezolid).

A total of 409,403 subjects were included in the study, with 79,369 in the pre-implementation period and 330,034 in the post-implementation arm. Average consumption of the targeted antibiotics, in defined daily doses (DDDs), was lower from 2016 through 2019 than in the pre-implementation period (233 vs 320 DDDs per 1,000 patient-days, P = 0.689), and antibiotic expenditures decreased by 28.45% in the first years of the program and remained relatively stable in subsequent years, with an estimated overall cumulative cost savings estimated at US $1,676,514.

Rates of healthcare-associated infections also fell, with incidence of Clostridioides difficile declining by 86.17%, ventilator-associated pneumonia falling by 75%, and central line-associated bloodstream infections falling by 94.12%.

The authors of the study note that many indirect expenses are also expected to decrease proportionally, including those associated with antibiotic resistance, antibiotic side effects, hospital-acquired infections, and increased length of hospital stay and readmission.
Jun 29 Antimicrob Resist Infect Control study

 

Rapid ID, susceptibility test aids stewardship, study finds

Implementation of a rapid identification (ID) and antimicrobial susceptibility test (AST) combined with pharmacy-driven antimicrobial stewardship in patients with gram-negative bacteremia and candidemia was associated with decreased use of broad-spectrum antibiotics, shortened time to targeted therapy, and fewer days in the hospital, researchers reported yesterday in Antimicrobial Agents and Chemotherapy.

In a pre-post quasi-experimental study conducted at a 288-bed community hospital in Maryland, researchers investigated the impact of the Accelerate Pheno system and Accelerate PhenoTest BC kit (AXDX), which can produce ID results in 2 hours and AST results in an additional 5 hours, on antimicrobial stewardship and clinical outcomes when compared with rapid genotypic testing.

The study included 200 patients (100 pre-AXDX implementation and 100 post-AXDX implementation) with positive blood cultures with gram-negative rods or candida species. The primary endpoints were time to first antibiotic intervention, time to targeted antibiotic therapy, and 14-day hospital mortality. Secondary endpoints included hospital and intensive care unit (ICU) length of stay (LOS), antibiotic intensity score at 96 hours, and 30-day readmission rates.

The final analysis included 84 patients in the pre-implementation group and 89 in the post-AXDX group. The results showed that time to first antibiotic intervention was significantly shorter in the post-AXDX group compared with the pre-AXDX group (8 vs 26.3 hours, P = .003), as was the median time to targeted therapy (9 vs 14.4 hours, P = .03). In addition, hospital LOS was shorter in the post-AXDX group compared with the pre-AXDX patients (6 vs 8 days, P = .002), and the antibiotic intensity score was lower (12 vs 16, P = .0002). Both groups had a comparable 14-day mortality (0% vs 3.6%, P = .11).

"Our results demonstrate that in a resource-limited community hospital setting, fast ID and AST via AXDX can be used in conjunction with clinical pharmacy services to positively impact patient care," the authors of the study wrote.
Jun 29 Antimicrob Agents Chemother abstract

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