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

Alliance forms to ensure accountability in AMR fight

Originally published Sep 22.

A collection of public health and infectious disease groups are banding together to ensure that the United Nations (UN), national governments, and other international bodies live up to their promise to tackle antimicrobial resistance (AMR).

The overarching aim of the Conscience of Antimicrobial Resistance Action (CARA) will be to hold the UN—including its subsidiary organizations, the World Health Organization (WHO), Food and Agriculture Organization (FAO), and the World Organization for Animal Health (OIE)—accountable for ensuring that countries live up to their commitments to create national action plans to reduce AMR. Those action plans are one of the key features of a political declaration on AMR that was adopted by UN member states yesterday.

In a press release, the alliance said its goals would include improving the surveillance of antibiotic use and resistance; helping define "appropriate antimicrobial use" and using this definition to guide stewardship efforts; ensuring universal access to antibiotics, especially in low-income countries; reinforcing judicious use of antimicrobials in agriculture; and supporting the development of new antimicrobials, diagnostic tests, and vaccines. CARA said it also plans to adopt clear, quantitative targets for meeting those goals and reporting on progress.

The nine founding members of the alliance are the Center for Disease Dynamics, Economics & Policy, the British Society for Antimicrobial Chemotherapy, the Antibiotic Resistance Action Center, the Center for Global Development, the German Center for Infection Research, the Pew Charitable Trusts, the Norwegian Institute of Public Health, the World Alliance Against Antibiotic Resistance, and the Center for Infectious Disease Research and Policy (publisher of CIDRAP News) at the University of Minnesota. The group plans to add partners from other sectors and countries.
Sep 20 CARA press release

Powerful new resistance mechanism found in Campylobacter

Originally published Sep 22.

Researchers in China have identified the emergence of a new mechanism that enhances resistance to multiple classes of antibiotics in Campylobacter bacteria.

The new mechanism is a variant of CmeABC, an efflux pump that confers multidrug resistance in Campylobacter. Efflux pumps are considered an important mechanism for antibiotic resistance; they help protect bacterial organisms by pushing antimicrobials and other toxins out of cells.

In the study, published this week in mBio, researchers characterized the variant—which they've coined RE-CmeABC—as a "super" efflux pump that is much more potent. It desensitizes Campylobacter to multiple classes of antibiotics, and it confers high levels of resistance to fluoroquinolones, which are the primary class of antibiotic used in Campylobacter infections. It also promotes the emergence of fluoroquinolone-resistant mutants under selection pressure.

The researchers said RE-CmeABC is especially prevalent in C jejuni and is emergent in chickens and pigs in China, the likely result of extensive use of antimicrobials in Chinese agriculture. In addition, their analysis found that RE-CmeABC can spread to other types of bacteria through horizontal gene transfer. They concluded that it will probably continue to spread in clinical isolates.

"Thus, enhanced efforts are needed to prevent its further dissemination," they wrote.

Campylobacter bacteria, particularly C jejuni, are the most common cause of diarrheal illness in humans. Infections usually result from consuming undercooked or contaminated poultry, unpasteurized milk, or contaminated water. Drug-resistant Campylobacter is listed as a serious antibiotic resistance threat by the US Centers for Disease Control and Prevention.
Sep 20 mBio study

HHS invests up to $287 million for possible drug-resistance solutions

Originally published Sep 21.

The US Department of Health and Human Services (HHS) announced today it has invested more than $67 million into partnerships with two drug companies to develop innovative antibiotics and diagnostics to help combat the growing threat of  multidrug-resistant bacterial infections, with options that could bring the investment to about $284 million.

The agreement, which will be managed by the Biomedical Advanced Research and Development Authority (BARDA), part of the HHS Office of the Assistant Secretary for Preparedness and Response (ASPR), involves The Medicines Company, headquartered in Parsippany, N.J., and Hoffmann-LaRoche Inc., part of the Roche Group, based in Basel, Switzerland, HHS said in a news release.

The partnership with The Medicines Company will continue to advance the development of multiple antibiotics, including Carbavance, a drug being developed to treat hospital-acquired bacterial pneumonia and ventilator-acquired bacterial pneumonia. Under a 2014 ASPR contract, Rempex, a wholly owned subsidiary of The Medicines Company, began evaluating Carbavance as a possible treatment for serious gram-negative infections, such as complicated urinary tract infections and infections caused by carbapenem-resistant Enterobacteriaceae.

The partnership with Roche will include continued development of diagnostic tests to detect specific viral and bacterial infections, which could help avoid unnecessary antibiotic prescriptions. The investment will also go toward an investigational antibiotic being developed to treat a variety of infections caused by drug-resistant bacteria in combination with another antibiotic. In addition, Roche will continue to review promising products that are in early research stages that could be added to the contract.

BARDA will provide more than $32 million over 4 years and potentially more than $132 million over 5 years to The Medicines Company and more than $35 million over 2 years and potentially more than $151.6 million over 5 years to Hoffmann-LaRoche Inc.

"The partnerships are the third and fourth ASPR has formed under other transaction authority," HHS said in the release. "All of the partnerships focus on developing new products to address the rising threat of antibiotic resistant infections."
Sep 21 HHS news release

Novel MRSA strain likely linked to poultry meat

Originally published Sep 21.

A study today in Clinical Infectious Diseases suggests that 10 human cases of MRSA (methicillin-resistant Staphylococcus aureus) were probably linked to eating contaminated poultry.

Though MRSA has previously been found in livestock, most people don't contract the "superbug" from foods. This study used genetic analysis to show how 10 cases of MRSA between 2009 and 2015 likely originated in turkey and chicken distributed throughout Europe. The genotype, LA-MRSA CC9/CC398, had never been found in Danish livestock, and the patients had no livestock exposure.

The study demonstrates both poultry and human adaptation of MRSA, which is resistant to most antibiotics. The authors wrote, "Isolates from the epidemiologically linked urban cases were nearly identical to each other, suggesting either transmission between these persons or acquisition from a common source, for example, a contaminated food product."

The authors recommend heightened surveillance for S aureus in consumer food products.
Sep 21 Clin Infect Dis study

World Bank predicts dire economic consequences from unchecked AMR

Originally published Sep 20.

A new report from the World Bank says rising antimicrobial resistance (AMR) has the potential to cause as much economic damage as the 2008 financial crisis.

The report, published yesterday by the World Bank Group, predicts that if rising AMR is not addressed, global GDP could fall by 1.1% to 3.8%, healthcare costs could grow by an additional $1.2 trillion annually, and as many as 28 million people would be pushed into extreme poverty by the year 2050. The brunt of the impact, the report says, would fall on lower- and middle-income countries, where higher disease prevalence would have a more significant effect on economic output.

The report also projects that rising AMR could result in significant losses for the world's farmers, with the decline in global livestock production ranging between 2.6% and 7.5%. In low-income countries, the decline could be as high as 11%.

"This report provides another timely reminder that rising drug resistance is a looming threat to our prosperity and sustained economic development in all parts of the world," Lord Jim O'Neill, chairman of the Review on Antimicrobial Resistance, said in a World Bank press release.

To avoid the financial consequences, the report recommends, among other things, greater investment in both human and veterinary health systems and in AMR surveillance, diagnostic, and containment capabilities. While such investments will be costly, especially for low-income nations, the report concludes that the expected benefits will be greater than the investment costs.
Sep 19 World Bank Group report on drug-resistant infections
Sep 19 World Bank press release

Study: Azithromycin shows little benefit in reducing asthma symptoms

Originally published Sep 20.

The addition of azithromycin to standard treatment for asthma attacks has little benefit in relieving symptoms and improving lung function, according to a study yesterday in JAMA Internal Medicine.

Azithromycin Against Placebo in Exacerbation of Asthma (AZALEA)—a randomized, double-blinded clinical trial at 31 medical centers in the United Kingdom—evaluated 4,582 people presenting to emergency care with asthma attacks from 2011 to 2014. Nearly half of screened patients (2,044, or 44.6%) were excluded because they had already received antibiotics, and only 390 eventually met study criteria. Researchers randomized a total of 199 patients to receive either 500 milligrams of azithromycin for 3 days (97 people) or placebo (106 people) within 48 hours of an asthma exacerbation.

No difference in average self-reported symptom scores occurred between the treatment and placebo group at any point during the 10 days following an attack. Researchers also found no significant difference in reported quality of life, lung function, or time to 50% reduction in asthma symptoms, the study said.

Nine patients in the azithromycin group and 12 in the placebo group tested positive for bacterial infections, and 36 patients overall tested positive for viral infections. The azithromycin group reported a greater number of adverse gastrointestinal and cardiac events compared to the placebo group (35 versus 24, and 4 versus 2, respectively), though patients receiving the antibiotic had a lower frequency of respiratory, thoracic, and mediastinal events, the authors said.

They concluded that the AZALEA study shows almost no benefit for prescribing azithromycin to patients suffering an asthma attack.

Two commentaries in the same issue of JAMA Internal Medicine offer insight into the trial’s results. The first, written by Guy G. Brusselle, MD, PhD, and Eva Van Braekel, MD, PhD, notes differences between the AZALEA trial and the Telithromycin, Chlamydophila, and Asthma Study (TELIKAST), the latter of which showed significant clinical benefit to administering the antibiotic telithromycin to patients having an asthma attack.

Brusselle and Van Braekel note that because all patients in the AZALEA study received a corticosteroid as part of standard care, the observed anti-inflammatory benefits of a macrolide antibiotic may have been substantially reduced. Additionally, only 5% of the AZALEA treatment group tested positive for a bacterial infection, as compared to 60% of patient in the TELICAST study, rendering antibiotic therapy more effective and appropriate in TELICAST participants, the authors said, adding, "Restricting the use of antibiotics to those patients with acute exacerbations who will benefit the most is therefore paramount."

Perhaps the greatest difference between the two trials stems from AZALEA’s exclusion of a large number of patients who already received antibiotics. Brusselle and Van Braekel note that this substantial exclusion may have caused selection bias, in which patients included in the study had already been deemed less likely to respond to antibiotic therapy.

A second commentary by Ateev Mehrotra, MD, MPH, and Jeffrey A. Linder, MD, MPH, notes the troubling overuse of antibiotics in the AZALEA study and offers a three-pronged approach for implementing greater antimicrobial stewardship while improving asthma care.

Mehrotra and Linder advocate for: (1) reframing the issue as an individual, rather than a public health, problem with significant risks to patient health when antibiotics are used inappropriately; (2) instituting social and behavioral interventions, such as prescription audits, for clinicians; and (3) using telemedicine to deter patients from seeking ambulatory care and antibiotic prescriptions for common illnesses.
Sep 19 JAMA Intern Med study
Sep 19 JAMA Intern Med commentary by Brusselle and Van Braekel
Sep 19 JAMA Intern Med commentary by Mehrotra and Linder

Multidrug-resistant strain of MRSA found in Memphis fitness centers

Originally published Sep 20.

An uncommon multidrug-resistant (MDR) strain of MRSA has been found on indoor surfaces in the United States for the first time, according to a study today in the American Journal of Infection Control.

Researchers from the University of Memphis and the Food and Drug Administration’s Southeast Regional Laboratory tested 32 samples from exercise machines, dumbbells, toilet handles, and stair handrails at four Memphis fitness centers.

All but three of the samples (29, or 90.6%) had evidence of S aureus colonies, 12 (37.5%) of which were identified as MRSA. All MRSA isolates were resistant to 7 to 12 antibiotics, and, troublingly, six were resistant to linezolid, one of the few remaining antibiotics considered effective against MRSA. The authors said that this marks the first time that linezolid-resistant MRSA has been identified in the Memphis area.

All MRSA isolates showed significant diversity of extracellular toxin genes and belonged to clonal complex or sequence type 59, a distinct genotype that is rare in the United States and has previously never been isolated from an indoor environment in the country, the authors said. They noted that further research is needed into potential transmission risks and hygiene precautions at fitness centers in the Memphis metropolitan region.
Sep 20 Am J Infect Control study