News Scan for Oct 04, 2018

News brief

Saudi MOH records new MERS case in Najran

The Saudi Arabian Ministry of Health (MOH) today recorded a new case of MERS-CoV for epidemiologic week 40, which is this week.

A 49-year-old man from Najran was diagnosed as having  MERS-CoV (Middle East respiratory syndrome coronavirus). The MOH said the man was hospitalized and likely exposed to the virus in a community setting. He had not reported recent contact with camels, a known risk factor.

The new case raises the global number of MERS-CoV cases reported since 2012 to 2,255 cases, at least 800 of them fatal, according to data from the World Health Organization.
Oct 4 MOH update


Study: New antiviral shortens flu symptoms in high-risk patients

The novel antiviral baloxavir marboxil shortened flu symptoms in people at high risk for flu complications, according to the latest phase 3 trials findings from the drug's developer Roche, according to a statement today. The company said it will detail the results on Oct 6 in a presentation during the IDWeek meeting in San Francisco.

The drug (Xofluza) was discovered in Japan by Shionogi, and earlier this year, Japan's health ministry approved it. In June, the US Food and Drug Administration (FDA) granted fast-track approval for the drug. In early September, results from phase 2 and 3 trials published in The New England Journal of Medicine suggested that baloxavir reduced flu symptoms by about a day and also found that the drug showed superior antiviral activity to oseltamivir .

The latest trial included people at high risk for flu complications, including adults age 65 and older and those with underlying health conditions such as asthma, chronic lung disease, morbid obesity, or heart disease. When compared to placebo, baloxavir significantly reduced the time to improvement of flu symptoms. The median time was 73.2 hours compared to 102.3 hours, similar to the two earlier studies, and the drug was well-tolerated with no new safety signals.

Sandra Horning, MD, Roche's chief medical officer and head of global product development, said in the statement, "This study adds to the growing body of evidence supporting baloxavir marboxil as a potential first-in-class antiviral flu treatment, and we plan to discuss these data with health authorities around the world."

The investigational drug, the first to be available as a single-dose treatment, represents the first new antiviral class in nearly 20 years. Roche said the FDA is expected to make its approval decision by Dec 24.
Oct 4 Roche press release
Sep 5 CIDRAP News story "New single-dose antiviral cuts flu symptoms, viral loads"


Phase 2 flu challenge finds mucosal protection for oral flu vaccine tablet

Vaxart, a biotechnology company based in South San Francisco, today announced the latest phase 2 flu challenge study findings for its oral tablet recombinant H1 flu vaccine, which suggest that it generates a strong mucosal immune response when compared to the Fluzone injectable quadrivalent flu vaccine. In a press release, the company said it would detail the findings on Oct 6 at the IDWeek meeting in San Francisco.

Sean Tucker, PhD, Vaxart's chief scientific officer, said in the statement that the vaccine elicited a significant expansion of mucosal homing receptor (β7+) plasmablasts to about 60% of all activated B cells, compared to Fluzone, which maintained a 20% baseline level. "We believe these β7+ plasmablasts are a key indicator of a protective mucosal immune response and a unique feature of our oral recombinant vaccines," he said. Tucker said the study found that the vaccine generates protective hemagglutinin inhibition (HAI) antibodies like conventional flu vaccines, but primary protection is through the mucosal mechanism, which provides a 39% reduction in illness compared to placebo. He said by comparison, Fluzone provided a 27% reduction in illness versus placebo, protecting primarily though HAI antibodies.

Wouter Latour, MD, Vaxart's chief executive officer, said mucosal immunity is the first line of defense against mucosal infections, and oral vaccines based on the company's system could help protect against a range of health threats, including flu, norovirus, and RSV.

The phase 2 study was supported by the Biomedical Advanced Research and Development Authority (BARDA), part of the US Department of Health and Human Services.
Oct 4 Vaxart press release
Oct 30, 2017, CIDRAP News scan "Vaxart's oral flu vaccine tablet shows promise in human challenge trial"


Scientists describe probe of first coconut-linked Salmonella outbreak

An investigation into clusters of Salmonella Chailey infections in the United States and Canada in 2017 found that the culprit was precut coconut pieces from a grocery chain, marking the first time coconut has been linked to a Salmonella outbreak in either country. Officials from the US Centers for Disease Control and Prevention (CDC) and their partners in Oregon and Canada reported their findings today in the latest issue of Morbidity and Mortality Weekly Report (MMWR).

Following the outbreak, two other outbreaks from different Salmonella subtypes have been reported in the United States, one involving dried coconut and the other frozen shredded coconut.

In early May of 2017, the CDC's PulseNet system identified a cluster of 14 matching isolates that had a rare pulsed-field gel electrophoresis (PFGE) pattern. Later that month, Canadian officials said they were investigating five Salmonella Chailey infections in British Colombia with the same PFGE pattern. Whole-genome sequencing found that all cases were highly related.

Patient interviews suggested the source was precut coconut pieces from one grocery store chain, and trace-back investigations in the United States and Canada implicated a single lot of the food imported from Indonesia, received frozen and repacked into smaller tubs for sale in the produce department, as the outbreak source. The authors said the grocery chain voluntarily recalled the coconut from their stores, which probably limited the outbreak's size and scope.

The group said recent Salmonella outbreaks have been caused by foods not typically associated with the bacteria, and they noted that yellowfin tuna imported from Indonesia in 2010 had the same PFGE pattern, providing more support that a food product from Indonesia was the source of the outbreak.

"In light of this finding, public health officials might consider raw coconut in investigations of Salmonella outbreaks among consumers of fresh foods," the authors wrote.
Oct 5 MMWR report

Stewardship / Resistance Scan for Oct 04, 2018

News brief

Topical phage treatment shows potential, weaknesses, in small clinical trial

The results of a small clinical trial in France show that a topical treatment containing a cocktail of bacteriophages successfully reduced bacterial burden in patients with infected burn wounds, but at a significantly slower rate than standard of care. The findings appeared yesterday in The Lancet Infectious Diseases.

In the randomized phase 1/2 PhagoBurn trial—the first randomized controlled trial to investigate phage therapy—25 patients with a confirmed burn wound that was clinically infected with Pseudomonas aeruginosa were recruited from nine hospitals in France and Belgium. The participants were randomly assigned 1:1 to receive topical treatment for 7 days with a cocktail of 12 natural lytic anti-P aeruginosa bacteriophages collected from hospital sewer water (PP1131) or standard of care (1% sulfadiazine silver emulsion cream). The primary end point was median time to sustained reduction in bacterial burden in two quadrants via a four-quadrant method, assessed by use of daily swabs in all participants.

Of the patients—recruited from Jul 22, 2015, to Jan 2, 2017—13 received  phage therapy and 12 received standard of care. The primary end point was reached in a median of 144 hours in the PP1131 group versus a median of 47 hours in the standard-of-care group (hazard ratio, 0.29; 95% confidence interval, 0.10 to 0.79; P = 0.018). In the PP1131 group, 6 of the 12 analyzable participants (50%) had a maximal bacterial burden versus 2 of 13 (15%) in the standard-of-care group. Adverse events were higher in the standard-of-care group (7/13, 54%) than in the PP1131 group (3/13, 23%). A follow-up study of bacteria isolated from patients whose PP1131 treatment failed showed resistance to low-phage doses.

Recruitment was stopped on Jan 2, 2017, because of concerns about patient exposure to insufficient phage concentration. On Mar 20, 2017, a data and safety monitoring board recommended stopping the trial because of the insufficient efficacy of PP1131.

The researchers say, however, that the clinically relevant reduction in bacterial burden observed in the group treated with the phage cocktail, and the smaller number of adverse events compared with standard of care, illustrate the potential of phage therapy.

"Although the effect was slower than in the control group, we found that our phage cocktail reduced bacterial burden in the infected wounds of patients with burns, one of the most difficult populations to treat, and something that, to our knowledge, has never been achieved in a human trial before," they write.
Oct 3 Lancet Infect Dis abstract


Study highlights high levels of inappropriate antibiotic prescribing in China

Chinese researchers employed actors pretending to be patients with one of three conditions that didn't require antibiotics and found that in 42% of 526 rural primary care encounters, physicians inappropriately prescribed the drugs anyway, according to a study today in the Journal of Antimicrobial Chemotherapy.

The study took place in village clinics and township health centers, the two lower tiers of China's three-tiered rural health system, in three geographically dispersed regions. The "patients" recruited for the study were trained to present cases of pulmonary tuberculosis, viral gastroenteritis, or unstable angina. The investigators also provided primary care providers with clinical vignettes to assess antibiotic prescribing habits.

The researchers found that providers inappropriately prescribed antibiotics in 221 of 526 patient visits, or 42% of the time. And compared with patient interactions, prescription rates were 29% lower in matching clinical vignettes (42% vs. 30%), suggesting practices don't always follow theoretical knowledge. Compared with vignettes assessing diagnostic and therapeutic knowledge jointly, prescribing rates were 67% lower in vignettes with the diagnosis revealed.

The authors conclude, "While a large proportion of overprescription may be due to factors such as financial incentives tied to drug sales and perceived patient demand, our findings suggest that deficits in diagnostic knowledge are a major driver of unnecessary antibiotic prescriptions."
Oct 4 J Antimicrob Chemother abstract


Point-of-care flu tests don't lower antibiotic prescribing, study finds

A meta-analysis today in Clinical Infectious Diseases of 13 studies involving point-of-care tests (POCTs) for influenza finds that they had no effect on admissions, return visits, or antibiotic prescribing but were associated with increased antiviral prescribing.

UK experts included in their review seven randomized and six non-randomized studies that involved more than 9,000 patients total. Most evidence came from pediatric emergency departments.

In randomized trials, POCTs had no effect on admissions, returning for care, or antibiotic prescribing, but they were tied to an increase in prescribing antivirals. In addition, further testing was reduced for full blood counts, blood cultures, and chest x-ray but not for urinalysis. Time in the emergency department was not changed. Fewer non-randomized studies reported these outcomes, with some findings reversed or lessened.

The researchers conclude, "Point-of-care testing for influenza influences prescribing and testing decisions, particularly for children in emergency departments."
Oct 4 Clin Infect Dis abstract

This week's top reads