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

Study finds high-dose colistin treatment has no mortality benefit

Treatment with high doses of colistin was found to have no mortality benefit for patients with carbapenem-resistant gram-negative infections, according to a study published yesterday in Clinical Infectious Diseases. But it was associated with greater nephrotoxicity.

The study used data from two prospective cohort studies performed from 2006 to 2009 and from 2012 to 2015 at two hospitals in Israel, involving 529 adult patients with invasive infections caused by carbapenem-resistant gram-negative bacteria susceptible to colistin. Of the 529 patients, 144 were treated with high doses of colistin (a median of 9 million international units [MIU] per day) and 385 were treated with lower-dose regimens (a median of 4 MIU/day).

The primary outcome was 28-day all-cause mortality. The hypothesis was that higher doses might translate to improved patient outcomes.

In an unadjusted analysis, 28-day mortality was 34.7% for the high-dose patients (50 deaths out of 144 patients) and 42.9% for the low-dose patients (165/385). In a propensity-matched analysis, which yields a more accurate comparison, high-dose mortality was 36.0% and low-dose mortality was 33.7%. When the researchers disregarded the loading dose, the numbers were even closer: 35.0% versus 33.9%, respectively. None of these differences was statistically significant.

There was no observed difference in earlier mortality or in other clinical outcomes, which included fever duration, length of hospital stay, and resistance development. The researchers did note, however, that renal failure was significantly more common in the patients receiving high doses of colistin. In addition, high-dose patients suffered seizures more frequently.
Oct 6 Clin Infect Dis abstract

CDC funds antibiotic stewardship research focused on the human microbiome

Originally published by CIDRAP News Oct 6.

The US Centers for Disease Control and Prevention (CDC) today awarded more than $14 million toward novel approaches to combat antibiotic resistance, including those that address a person's microbiome, or the vast population of microorganisms that live inside and on the body.

The awards, made through the CDC's Broad Agency Announcement, support activities for 34 projects under the agency's Antibiotic Resistance Solutions Initiative, the CDC said in a news release. The initiative, which also provides funding for state health departments and other partners, implements the tracking, prevention, and antibiotic stewardship activities outlined in the White House's National Action Plan for Combating Antibiotic-Resistant Bacteria, developed last year.

The awards will go to 22 universities, 2 nonprofits (The Joint Commission and OpenBiome), and one commercial company—Synthetic Biologics, Inc., of Rockville, Md. Some institutions will be conducting more than one project.

Antibiotics can disrupt the microbiome by changing the balance of good and bad bacteria, which can make patients susceptible to drug-resistant bacteria. Those resistant bacteria can then spread to other people, especially those who also have a disrupted microbiome or compromised immune system.

The research funded by the awards will explore the relationships between antibiotics, the microbiome, and the consequences of widespread antibiotic use. Areas of research include how antibiotics disrupt a healthy microbiome, how a disrupted microbiome puts patients at risk, and how antibiotic stewardship can be improved to better protect the microbiome.

"Understanding the role the microbiome plays in antibiotic-resistant infections is necessary to protect the public's health," said CDC Director Tom Frieden, MD, MPH.
Oct 6 CDC news release

BARDA awards contract for development of rapid diagnostic test

Originally published by CIDRAP News Oct 6.

The Biomedical Advanced Research and Development Authority (BARDA) has awarded healthcare technology company DNA Electronics an $8.5 million contract to support development of a next-generation sequencing platform for rapid diagnosis of antimicrobial-resistant infections and influenza, according to news releases from the Department of Health and Human Services (HHS) and the company.

The money will enable the company to support further development and testing of its Genalysis platform, which can sequence and analyze the DNA from blood samples or swabs and identify the pathogen within 2 to 4 hours. The technology would allow doctors to quickly determine the bacteria responsible for infections and their associated level of resistance. It would also diagnose the specific strain of influenza virus in a flu patient. Under current methods, obtaining that information takes several days.

"More rapid diagnoses will allow clinicians to ensure the right treatment is being given, providing faster care for their patients and potentially curbing the spread of pathogens," Richard Hatchett, MD, acting director of BARDA, said in a statement. "This platform could help enable a faster and more accurate public health response to pandemic influenza and antibiotic resistant infections."

The first product will be a rapid blood-to-result diagnostic system for serious bloodstream infections leading to sepsis, which is responsible for 200,000 US deaths a year. Company officials say the device can be operated by users who don't have specific training in sequencing and has the potential to save lives, reduce time spent in critical care, and improve antibiotics stewardship.

The device is currently in late-stage testing and development. If it receives approval from the Food and Drug Administration (FDA), it could be on the market in 2018. The BARDA contract could be extended for up to 4 years and $51.9 million as the company seeks FDA clearance.

BARDA is a division of the Assistant Secretary for Preparedness and Response within HHS.
Sep 30 HHS press release 
Sep 30 DNA Electronics press release

UK researchers note worrisome antibiotic-resistant Shigella cluster

Originally published by CIDRAP News Oct 5.

A UK study this week notes highly resistant Shigella sonnei isolates from men who have sex with men (MSM) who had engaged in high-risk activities, while Canadian scientists report a different antibiotic-resistant Shigella strain in a man with HIV, according to separate reports in Emerging Infectious Diseases.

In the first study, researchers from Public Health England report identifying a cluster of S sonnei in November 2015 that showed high levels of resistance to amoxicillin, ceftriaxone, tetracycline, sulphonamides, trimethoprim, and azithromycin and produced extended-spectrum beta-lactamase (ESBL). Those findings led the agency to sequence about 70% of S sonnei isolates obtained from hospital labs since August 2015.

Their investigation revealed nine patients whose fecal specimens tested positive for resistant S sonnei. Their gastrointestinal symptoms began from September to late December 2015. All seven patients who answered detailed questions about sexual history reported having male partners. Six reported sexual activities considered to be high risk for Shigella transmission, such as oral-anal contact and attendance at sex parties.

Isolates from all nine men produced ESBL and exhibited macrolide resistance. Whole-genome sequencing showed a close relationship among the isolates, which harbored a previously identified plasmid that has since acquired a mobile element, making it more easily transferred to another pathogen, the authors reported. No epidemiologic links were found among the patients, and no point sources were identified, making foodborne acquisition less likely.

In Canada, the researchers reported S flexneri in a 53-year-old HIV-positive MSM that was resistant to ampicillin, trimethoprim/sulfamethoxazole, nalidixic acid, ciprofloxacin, tetracycline, and chloramphenicol. It was susceptible to ceftriaxone, cefixime, ertapenem, and gentamicin and was also isolated last year.
Oct 3 Emerg Infect Dis UK report
Oct 3Emerg Infect Dis Canadian case report

Study links nations' poverty to higher antimicrobial resistance levels

Originally published by CIDRAP News Oct 5.

Researchers from India reported yesterday that countries with lower per-capita income have higher levels of antimicrobial resistance (AMR).

Writing in the International Journal of Infectious Diseases, a trio of scientists compared 2013-2014 gross national income per capita (GNIPC) with the prevalence of three common resistant bacteria: third-generation cephalosporin (3GC)-resistant Escherichia coli, methicillin-resistant Staphylococcus aureus (MRSA), and 3GC-resistant Klebsiella. Their analysis included 43 countries.

The researchers found that, for each log increase in GNIPC, levels of 3GC-resistant E coli, 3GC-resistant Klebsiella, and MRSA dropped 11.3%, 18.2%, and 12.3%, respectively. The association was stronger, however, for E coli and Klebsiella than for MRSA.

The authors concluded, "Our results underscore the urgent necessity of new policies aiming at reducing AMR in resource-poor settings."
Oct 4 Int J Infect Dis study

Livestock-associated MRSA found in UK pork products

Originally published by CIDRAP News Oct 3.

Samples of UK-produced pork products have tested positive for a livestock strain of methicillin-resistant Staphylococcus aureus (MRSA), according to a report today by The Guardian.

Working in conjunction with the Bureau of Investigative Journalism (BIJ) and the Alliance to Save Our Antibiotics, the paper found that 3 out of 97 samples of minced pork sold in UK supermarkets Asda and Sainsbury's tested positive for MRSA CC398. BIJ reports that the bacterium in all 3 samples was fully resistant to tetracyclines and partially resistant to fluoroquinolones, which are widely used in intensive pig farming. The two Asda samples were also resistant to macrolide and lincosamide antibiotics, while the Sainsbury sample was resistant to trimethoprim.

Officials with the Department for Food, Environment and Rural Affairs (Defra) told The Guardian that if meat is handled and prepared properly, the risk for human infection is low. The main initial effect of MRSA CC398 is a skin infection, but it can have more serious consequences in people with compromised immune systems.

According to Eurosurveillance, CC398 is the dominant MRSA strain in European livestock today, with pigs being the primary host. It's also become a frequent cause of human colonization and disease on the continent, mainly affecting people who have direct livestock contact and members of their household. But studies in Denmark, where the reservoir of MRSA CC398 in pigs has been expanding, have shown some spillover into patients with no direct exposure to livestock. The Guardian and BIJ report that an estimated 12,000 people in Denmark have contracted MRSA CC398 in the past decade.

The Guardian and BIJ also found that, because of a regulatory loophole, live breeding pigs entering the UK from Denmark are not screened for MRSA CC398 because it's not classified as a notifiable disease by Public Health England. That means the UK's pig herd could be at risk of wider contamination.

Defra officials told The Guardian that the government is reviewing options for surveillance.
Oct 3 Guardian story
Oct 3 BIJ report
Sep 17, 2015, Eurosurveillance research article

Investigation reveals antibiotic overprescribing by UK online pharmacies

Originally published by CIDRAP News Oct 3.

Britain's General Medical Council (GMC) says it's launching a probe into UK-based online pharmacies after a BBC investigation revealed that some are inappropriately selling antibiotics to customers.

In the BBC investigation, a reporter posing as a 16-year-old patient was easily able to obtain antibiotics for a dental infection, an ear infection, and a urinary tract infection over the course of 3 days after filling out an online questionnaire. The online requests were all approved by the same doctor, and the reporter—who's also a general practitioner—received a selection of antibiotics within 24 hours. Many of the antibiotics were not appropriate to the infection for which they were requested.

Of the 17 online pharmacies investigated, the BBC found that many were not following the guidelines for antibiotic prescribing put forward by Britain's National Institute for Health and Care Excellence.

"Overprescribing of antibiotics risks the health of us all, and it is important that every practising doctor in the UK reflects on current guidance," GMC chief executive Niall Dickson said in a statement. "Although we cannot comment on specific investigations, the BBC has produced serious allegations and we will be looking into them carefully."

The report comes at a time when Britain's National Health Service (NHS) has been urging doctors to curb overprescribing of antibiotics. In May, the NHS announced it would offer funding to hospitals and other providers that reduce inappropriate prescribing.
Oct 2 BBC investigation
Oct 2 GMC statement