ASP Scan (Weekly) for Sep 20, 2019

Antibiotic resistance in pork chops
;
XDR Salmonella in DRC
;
AMR and universal health coverage
;
Staph bacteremia in Australia
;
Monoclonal antibodies for resistant infections
;
Early diagnostics in sepsis
;
CARB-X funds novel antibiotic

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

USDA study finds resistance levels aren't lower in antibiotic-free pork

Originally published by CIDRAP News Sep 19

A new study by scientists from the US Department of Agriculture (USDA) has found similar levels of antimicrobial resistance (AMR) in pork chops from pigs raised without antibiotics and those raised conventionally.

For the study, published yesterday in the Journal of Food Protection, USDA researchers cultured bacteria from 372 pork chop samples from three food service suppliers that obtained their products from multiple harvesting facilities. Of the 372 samples, 190 came from conventional production systems and 180 came from "raised without antibiotics" (RWA) production systems. They focused on AMR in Escherichia coli, Salmonella enterica, Enterococcus spp, and Staphylococcus aureus. In addition, they evaluated DNA from the samples for the presence of 10 AMR genes.

The results of the analysis showed that levels of eight types of resistant bacteria in the conventional and RWA samples—tetracycline-resistant E coli, Salmonella, and Enterococcus; third-generation cephalosporin-resistant E coli and Salmonella; nalidixic acid-resistant Salmonella; erythromycin-resistant Enterococcus; and methicillin-resistant S aureus—were similar regardless of the antibiotic use claims. The prevalence of AMR genes were also similar. Overall, the populations of AMR bacteria in the samples were a small fraction of the aerobic bacterial population.

The authors of the study, who noted similar findings in conventionally raised and RWA ground beef last year, say that because the samples came from only three suppliers, they can't extrapolate the findings to the entire US retail pork supply. They also note that the findings do not conflict with reports that antibiotic use during swine production increases the presence of AMR bacteria in pig feces.

They conclude, however, that the study provides new evidence that antibiotic use in US swine production does not significantly increase the presence of AMR bacteria in pork products.
Sep 18 J Food Prot abstract 
Nov 28, 2018, CIDRAP News story "Study finds resistance levels not lower in antibiotic-free burger meat"

 

Scientists outline XDR Salmonella Typhimurium in DR Congo

Originally published by CIDRAP News Sep 19

As if the Democratic Republic of the Congo (DRC)—which has been wracked by outbreaks of Ebola, measles, polio, and other diseases—didn't have enough public health crises, researchers today highlighted another serious concern: a strain of highly resistant Salmonella.

Writing in Nature Communications, the team described how they used whole-genome sequencing to analyze 81 blood samples containing Salmonella enterica serovar Typhimurium—a common cause of bloodstream infections in sub-Saharan Africa—that were collected from 2008 to 2016. The scientists found that 54 of these isolates demonstrated resistance to azithromycin and compared them with 27 Salmonella Typhimurium isolates susceptible to the antibiotic.

They found that all 54 resistant isolates were also extended-spectrum beta-lactamase–positive, and 51 were also multidrug-resistant (MDR) and could therefore be classified as extensively drug-resistant (XDR). These XDR isolates belonged to the ST313 sublineage II.1. They also demonstrate resistance to ceftriaxone, which, in addition to azithromycin, is the typical alternative antibiotic used to combat MDR Salmonella, so the only treatment available in the DRC are fluoroquinolones, the authors write.

They also note, "Whole genome sequencing reveals that ST313 II.1 isolates have accumulated genetic signatures potentially associated with altered pathogenicity and host adaptation, related to changes observed in biofilm formation and metabolic capacity." They say the sublineage may have emerged in the country around 2004. 
Sep 19 Nat Commun study

 

Report: Universal health coverage may be hindered by antibiotic resistance

Originally published by CIDRAP News Sep 18

Failure to manage rising AMR could hinder the advancement of universal health coverage, and must be addressed if universal health coverage is to be achieved, according to a new policy brief from advocacy group ReAct.

Based on insights from experts from 33 countries who attended a July conference organized by ReAct and the South Centre, the report argues that AMR poses a major threat to the financing of universal health coverage because it will lead to resistant infections that require more expensive antibiotics and longer hospitalization, as well as increased medical risks and costs from surgery, chemotherapy, and organ transplants. This will make healthcare more expensive for both the individual and for society and undermine the essence and goals of universal health coverage.

"Sustainable financing of universal health coverage needs to consider the current and long-term risks of antimicrobial resistance: the choice is to pay now, or pay much more later," the authors of the report write.

They add that, for a universal health strategy to be successful, it has to address AMR by placing more emphasis on infection prevention and control, investing more in training and education for health professionals, strengthening monitoring and surveillance of resistant pathogens, and ensuring that antibiotics are accessible but not used irrationally. The report also calls for more political leadership and a financing strategy that rewards better performance in managing AMR.

The report concludes, "The expansion of primary health care, access to essential medicines and diagnostics, access to clean water and sanitation, prevention of infections, increased vaccination coverage and other measures are important components of antimicrobial resistance programs that improve quality of care. This illustrates that antimicrobial resistance and universal health coverage go hand-in-hand." 

The report comes ahead of the United Nations high-level meeting on universal health coverage, which will be held on Sep 23 during the UN General Assembly in New York.
Sep 17 ReAct policy brief

 

Report highlights prevalence of MRSA bacteremia in Australia

Originally published by CIDRAP News Sep 18

Roughly one in five S aureus bacteremia (SAB) isolates collected from Australian hospitals in 2017 were methicillin-resistant, according to a new report from the Australian Group on Antimicrobial Resistance.

Of the 2,515 isolates collected from 36 institutions participating in the Australian Staphylococcus aureus Sepsis Outcome Programme (ASSOP) in 2017, 19% were methicillin-resistant S aureus (MRSA). Among the MRSA isolates, resistance to non-beta-lactams was common, with approximately 42% of MRSA isolates also showing resistance to erythromycin and ciprofloxacin and 14% showing resistance to co-trimoxazole, tetracycline, and gentamicin. In addition, 31.3% of MRSA isolates were multidrug-resistant. Resistance to non-beta-lactam antimicrobials was largely attributed to two healthcare-associated MRSA clones: ST22-IV and ST239-III.

The 30-day mortality associated with methicillin-resistant SAB was 18.9%, compared with 14% for methicillin-susceptible SAB.

The report notes that while the percentage of methicillin-resistant SAB has decreased significantly in Europe (from 23.9% in 2009 to 16.9% in 2017) and in other parts of the world, it has remained stable in Australia (19.1% in 2013 to 19.0% in 2017), possibly because of a significant rise in community-associated MRSA cases.

"ASSOP 2017 has demonstrated antimicrobial resistance in SAB in Australia continues to be a significant problem and continues to be associated with a high mortality. This may be due, in part, to the high prevalence of methicillin-resistant SAB in Australia, which is significantly higher than most EU/EEA countries," the report concludes. "Consequently MRSA must remain a public health priority and continuous surveillance of SAB and its outcomes and the implementation of comprehensive MRSA strategies targeting hospitals and long-term care facilities are essential."
Sep 16 ASSOP 2017 report

 

NIH to fund monoclonal antibody treatment for resistant pathogens

Originally published by CIDRAP News Sep 18

Biotechnology company Inovio Pharmaceuticals announced yesterday that it has received a $4.6 million grant from the National Institutes of Health (NIH) to develop a treatment for multidrug-resistant infections that's based on its DNA-encoded monoclonal antibodies (dMAb) program.

According to a company press release, Inovio, in collaboration with The Wistar Institute, has demonstrated that the dMAb technology can effectively treat multidrug-resistant infections in animal models. The platform uses synthetic gene sequences that instruct a patient's cells to produce an encoded monoclonal antibody that specifically targets the bacterial pathogen. The NIH grant will support additional pre-clinical studies.

"Antimicrobial resistance represents an expanding global public health concern and a tremendous market opportunity for Inovio," said company president and chief scientific officer Laurent Humeau, PhD. "Our ultimate goal is to create a paradigm shift approach to monoclonal antibody technology that results in a pipeline of high impact dMAb products, which can be developed with corporate partnerships, external funding, and collaborations. This grant from the NIH will further this goal."

Inovio is also developing a dMAb product to treat and prevent Zika infection.
Sep 17 Inovio press release

 

Study underscores need for early diagnostic tests in severe sepsis

Originally published by CIDRAP News Sep 17

US and Canadian researchers, writing in the Annals of Internal Medicine today, said they have determined that, among patients with severe manifestations of sepsis, initiation of empirical antimicrobial therapy significantly reduces the sensitivity of blood cultures drawn shortly after treatment began—underscoring the need for early diagnostic blood tests.

Administering antimicrobial agents such as antibiotics before obtaining blood cultures could decrease the time it takes for patients to receive life-saving drugs and improve outcomes—especially in patients who have severe sepsis, or an infection in the bloodstream—but scientists are unsure how this strategy affects diagnostic sensitivity.

To determine the effects of early antimicrobial initiation, the team analyzed data on 325 patients in seven North American emergency departments who had severe manifestations of sepsis. They found that 31.4% of the patients tested positive for pathogens in their blood before early antimicrobial therapy was begun, but only 19.4% tested positive afterward. The absolute difference in the proportion of positive blood cultures between pre- and post-antimicrobial testing was 12.0%, and the sensitivity of post-antimicrobial culture was only 52.9%.

The authors point out that international guidelines call for early (before-therapy) testing with suspected sepsis. "Our study has, for the first time ever, produced clear evidence supporting current sepsis guidelines and underscores the urgent need for proper sepsis protocols," said David Sweet, MD, senior study author, in a University of British Columbia news release. "Emergency rooms must place more emphasis on sepsis guidelines and make sure they have the resources to implement them."

The study was funded by Vancouver Coastal Health, St. Paul's Hospital Foundation Emergency Department Support Fund, the Fonds de recherche Sante–Quebec, and the Maricopa Medical Foundation.
Sep 17 Ann Intern Med abstract
Sep 17 University of British Columbia news release

 

CARB-X to fund development of novel antibiotic for gram-negatives

Originally published by CIDRAP News Sep 17

CARB-X announced today that it has awarded $2.2 million to UK-based Procarta Biosystems to develop a new class of antibiotics to treat dangerous gram-negative pathogens.

The money from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) will help fund preclinical development of Procarta's lead antibiotic candidate, PRO-202, which is based on the company's novel oligonucleotide transcription factor decoy (TFD) platform. TFDs are designed to kill gram-negative and gram-positive bacteria by preventing expression of genes they need to survive and cause infection.

If successfully developed and approved, PRO-202 could be used to treat complicated urinary tract and intraabdominal infections caused by gram-negative ESKAPE pathogens (which include Klebsiella pneumoniae, Acinetobacter baumannii, Pseudomonas aeruginosa, and Enterobacter species).

"CARB-X selects innovative projects that target the most serious drug-resistant bacteria and that could, if successful, be a leap forward in the fight against deadly drug-resistant superbugs," CARB-X executive director Kevin Outterson, JD, said in a press release. "The Procarta project is the type of cutting-edge innovation that can make headway against the global threat of drug-resistant bacteria."

Procarta could receive an additional $7 million if certain project milestones are met. Part of the funding comes from the UK government's Global AMR Innovation Fund. 
Sep 17 CARB-X press release 

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