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Stewardship / Resistance Scan for May 27, 2021

Stewardship / Resistance Scan for May 27, 2021

CARB-X to fund development of CRISPR-based drug for E coli infections

CARB-X announced today that it is awarding up to $3.9 million to a Danish microbiome biotechnology company to develop a CRISPR-based drug to prevent Escherichia coli infections in cancer patients.

The award will help Copenhagen-based SNIPR BIOME ApS develop its lead drug candidate, SNIPR001, which uses CRISPR/Cas DNA editing technology to selectively eradicate E coli bacteria in the gut and prevent translocation of the bacteria to the bloodstream while sparing other beneficial bacteria in the patient’s microbiome.

Cancer patients with hematologic malignancies are often at increased risk of bloodstream infections because of the disease and chemotherapy treatment, with E coli posing a heightened risk. They are typically treated with broad-spectrum antibiotics.

“There is an increasing awareness of the importance for human health of microbial diseases and anti-microbial resistance,” SNIPR BIOME Chief Medical Officer Milan Zdravkovic, MD, PhD, said in a CARB-X (the Combating Antibiotic-Resistant Bacteria Biopharmaceutical Accelerator) press release. “We see that SNIPR001 has the potential to contribute to addressing unmet medical needs in a novel way in people at high risk of severe E. coli infections, and we look forward to working with CARB-X in bringing SNIPR001 into clinical trials.”

SNIPR BIOME may be eligible for an additional $6.3 million if the project achieves certain milestones. The company hopes to begin a first in-human study in the first half of 2022.

Since its launch in 2016, CARB-X has announced 90 awards to product developers in 12 countries. The awards are worth more than $337 million.
May 27 CARB-X press release


New WHO guidance aims to help nations implement stewardship steps

The World Health Organization (WHO) has published new guidance for countries on how to implement antimicrobial stewardship (AMS) activities in healthcare facilities in an integrated, comprehensive manner.

The guidance, which was requested by member states and is intended for policy makers at national ministries of health and national antimicrobial resistance (AMR) coordinating bodies, was developed by WHO staff with input from an international group of experts, including those from the University of Minnesota’s Centers for Infectious Disease Research and Policy, publisher of CIDRAP News.

The guidance is organized into five key pillars and 12 interventions that countries need to consider to implement comprehensive and integrated AMS activities in healthcare facilities. The WHO defines AMS as a coherent set of integrated actions that promote responsible and appropriate use of antimicrobials and help improve patient outcomes across the continuum of care.

The five key pillars of the guidance are: (1) Establish and develop national coordinating mechanisms for antimicrobial stewardship and develop guidelines; (2) ensure access to and regulation of antimicrobials; (3) improve awareness, education, and training; (4) strengthen water, sanitation, and hygiene and infection prevention and control (IPC); and (5) conduct surveillance, monitoring, and evaluation.

Interventions include establishing a national coordination mechanism for AMS activities that can function at national, subnational, and district levels, developing national treatment and stewardship guidelines, regulating responsible and appropriate use of antimicrobials, implementing IPC core components in health facilities, and establishing surveillance systems for antibiotic use and AMR.

“AMS activities are best implemented in an integrated manner to optimize antimicrobial prescribing and ensure patient and public safety,” the guidance states. “It is important that the central coordination unit takes the lead, involving all relevant stakeholders in national policy development and strategic planning processes to identify the priority objectives, inputs and resources required and, finally, to implement the policy.”

The guidance also advises that the central coordination unit should consider national and local context and the structure of the health system in carrying out AMS activities, prioritize activities that are likely to provide the greatest benefit, and ensure strong links between relevant areas and disciplines related to AMR.
May 20 WHO policy guidance


Study examines inadequate antibiotics in patients tested for COVID-19

Inadequate antibiotic therapy (IET) in hospital patients with positive bacterial cultures who were tested for SARS-CoV-2 was associated with a significant increase in mortality and longer hospital stays compared with those who received adequate therapy, US researchers reported yesterday in Open Forum Infectious Diseases.

The multicenter retrospective study, conducted by scientists with Merck & Co. and Becton, Dickinson and Company, looked at in-hospital mortality and hospital and intensive care unit (ICU) length of stay (LOS) in patients who were tested for SARS-CoV-2 and had a positive bacterial culture at 201 US hospitals from March to November 2020. While high rates of empiric antibiotic use have been reported in COVID-19 patients throughout the pandemic, little research has been conducted on the impact of IET—defined as therapy not active against the identified bacteria or no antibiotic therapy in the 48 hours following culture—on patient outcomes.

Of the 438,888 patients who were tested for COVID-19, 39,203 (8.9%) had positive bacterial cultures. Among the patients with positive cultures, 3,764 (9.4%) were SARS-CoV-2–positive, 74.4% had a gram-negative pathogen, and 25.6% had a gram-positive pathogen. Overall, 17,295 (44.1%) of these patients received IET, with the absence of empiric treatment within 48 hours more common than antibiotic therapy that was not active against the identified bacteria.

In multivariable analysis, IET was associated with a 21% increase in mortality (odds ratio, 1.21; 95% confidence interval, 1.10 to 1.33) compared with adequate antibiotic therapy, and a significant increase in hospital LOS (16.1 days vs 14.5 days). The difference in ICU LOS was not statistically significant (8.2 days vs 8.0 days). Both mortality and hospital LOS findings remained consistent for patients who tested positive for SARS-CoV-2 and those who tested negative.

“Our data indicate that underlying gram-positive and gram-negative bacteria continue to play an important role in hospital outcomes during the COVID19 pandemic, and one with the potential to be adequately managed to help ensure more favorable outcomes,” the authors wrote, adding that they hope the study enables stewardship programs to educate and contain IET in hospitals for all patients with bacterial infections.
May 26 Open Forum Infect Dis abstract

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