Stewardship / Resistance Scan for Aug 31, 2020

News brief

Paper highlights promise of bacteriophage therapy

A new paper in Open Forum Infectious Diseases lays out some of the lessons learned from cases of antibiotic-resistant infections treated with bacteriophage therapy.

For the paper, researchers with the Center for Innovative Phage Applications and Therapeutics (IPATH) at the University of California, San Diego, reviewed nearly 2 years of consult requests for bacteriophage therapy and examined outcomes from the first 10 cases at the center treated with intravenous (IV) bacteriophage therapy. IPATH was launched in 2018 to expand clinical use of the bacteria-killing viruses against multidrug-resistant infections.

Of the 785 requests from patients and physicians, 82% were for treatment of bacterial infections, primarily those caused by Pseudomonas aeruginosa, Staphylococcus aureus, and Mycobacterium abscessus. Bacteriophage therapy was administered to 17 of 119 patients in whom it was recommended, and the median time from request to administration was 170 days.

Review of the first 10 cases, seven of which had successful outcomes, showed that administration of IV and nebulized bacteriophage therapy appears safe, may be safely administered by outpatients, and can be used to suppress infections. The review also found that bacterial resistance to bacteriophage therapy can develop but can be overcome with new phages, that combining phages and antibiotics can lead to successful outcomes despite the presence of in vitro antibiotic resistance, and that treatment failure can occur despite in vitro phage susceptibility.

"In conclusion, our experience with BT [bacteriophage therapy] for a variety of indications highlights the promise of BT for multiple clinical indications," the authors of the paper wrote. "Significant work is needed to identify predictors of success and for design of clinical trials that will lead to more widespread use."
Aug 27 Open Forum Infect Dis abstract

European drug makers call for new reimbursement models for antibiotics

The BEAM (Biotech companies in Europe combating Antimicrobial Resistance) Alliance late last week urged the European Union (EU) and individual member states to adopt new reimbursement models for antibiotics.

In a paper on its website, the alliance, which includes 70 small- and medium-sized European companies involved in antibiotic development, called on the European Commission to create a new pull incentive framework that would help make new antibiotics more commercially viable and to provide guidance to member states on the size of the incentives that would be required.

The group also encouraged member states to champion and adopt a new EU legislative framework that would encourage the development of new antibiotics and to create new reimbursement models similar to those adopted in the United Kingdom and Sweden.

"Because new antibiotics are (appropriately) held in reserve, developers of new medicines have struggled financially or have gone bankrupt," the alliance said. "The BEAM Alliance and the co-signatories of this paper urge the EU and its member states to urgently act and fix the broken economics around investment into the development and commercialization of antimicrobials."

In another paper posted on its website last week, the alliance applauded the launch of the AMR Action Fund, a nearly $1 billion effort by pharmaceutical companies to support late-stage antibiotic development announced earlier this summer. But the group noted that the fund "must be matched by a commercial ecosystem that is supportive of innovation in the field, so that the antibacterial drugs developed as a result of this funding can be truly viable from a market as well as scientific and clinical perspective."
Aug 28 BEAM Alliance paper on new reimbursement models
Aug 27 BEAM Alliance reflection paper on the AMR Action Fund

News Scan for Aug 31, 2020

News brief

US cell phone data: Staying home amid lockdowns may stem COVID-19

US counties with large declines in cell phone activity at workplaces, transit stations, and stores and concomitant increases in home activity during COVID-19 lockdowns had lower rates of coronavirus infections 5, 10, and 15 days later, according to a study published today in JAMA Internal Medicine.

The researchers made 22,124 to 83,745 daily observations of cell phone location data from 949 to 2,740 counties, depending on data availability, from Jan 22 to May 11 and compared them with COVID-19 growth rates.

Growth of COVID-19 cases was 45.5% lower in counties in the lowest quartile of activity in retail stores than in those with the highest quartile, while counties with the most residential activity had a 19% lower COVID-19 growth rate at 15 days than those with the least.

Overall, cell phone activity outside the home increased roughly 0.5% compared with in-home activity per day that the stay-at-home measures were in place, suggesting waning adherence over time.

After adjusting for county population, case rates, and state-level factors, rural counties had smaller reductions in cell phone activity at workplaces, transit stations, and stores and greater reductions in visits to parks and home activities than did urban counties.

Counties in states with higher proportions of older adults, children, black residents, and people living in poverty; more per-capital hospital beds; and lower population density had the smallest reductions in workplace cell phone activity. Conversely, county residents stayed home more in states with a lower proportion of older adults, higher population density, greater economic productivity, lower rates of the uninsured, greater proportion spent on healthcare, fewer people living in poverty, and higher case rates.

"Reductions in workplace activity and increases in residential activity were higher in counties and on days where/when there was a greater number of new cases, and thus there was likely a higher perceived risk of infection," the authors said. "Counties with a high rate of cases were likely to also have more restrictions in place."

The researchers said that their findings support cell phone location monitoring to predict pandemic trends.
Aug 31 JAMA Intern Med study

Multicenter study suggests stealthy COVID-19 spread by children

Twenty of 91 children (22%) diagnosed as having COVID-19 in a South Korean study had no symptoms, and most symptoms in clinically ill children went unrecognized or developed only after diagnosis, suggesting that this age-group may silently spread coronavirus in the community.

The study, which involved pediatric contacts of people with COVID-19 at 22 medical centers from Feb 18 to Mar 31, was published late last week in JAMA Pediatrics. Of the 71 symptomatic children, 47 (66%) had symptoms that went unrecognized as coronavirus symptoms, and 18 (25%) developed symptoms only after diagnosis, while only 6 (9%) were diagnosed at the time of illness onset.

Of the 91 children, 22 (24%) had lower respiratory tract infections. RNA from SARS-CoV-2, the virus that causes COVID-19, was found in upper respiratory samples for a mean of 17.6 days among all patients and for a mean of 14.1 days in children with no symptoms. Mean duration of virus RNA detection was not different for children with upper versus lower respiratory tract infections (18.7 days vs 19.9 days). All patients recovered from their infections.

Median patient age was 11 years, 53 (58%) were boys, and 6 (7%) had underlying medical conditions. Fifty-seven children (63%) were infected by household members.

The authors called for heightened surveillance with COVID-19 testing to allow detection of the virus in children with no, mild, or nonspecific symptoms.

In a commentary in the same journal, Roberta DeBiasi, MD, MS, and Meghan Delaney, DO, MPH, of George Washington University pointed out that most ill children had symptoms for as long as 28 days before diagnosis, although they were presumably being monitored because they were a contact of a COVID-19 patient.

"This highlights the concept that infected children may be more likely to go unnoticed either with or without symptoms and continue on with their usual activities, which may contribute to viral circulation within their community," they said.
Aug 28 JAMA Pediatr study and commentary

Ebola sickens 2 more in DRC outbreak, 109 total, with 47 deaths

Tests confirmed Ebola infections in 2 more people in the Democratic Republic of the Congo (DRC) Equateur province outbreak, raising the total to 109 cases, the World Health Organization (WHO) African regional office said today on Twitter.

No new deaths were reported, keeping the fatality count at 47.

The outbreak, the DRC's 11th involving Ebola, was first detected in early June in the same area where the country's ninth outbreak occurred in 2018.

Health officials are concerned about the latest outbreak, as responders grapple with COVID-19 and other health challenges and stretched resources. Also, the outbreak is occurring across a wide region, which includes both difficult-to-access areas and Mbandaka, the provincial capital.
Aug 31 WHO African regional office tweet