Genentech reports promising findings for baloxavir flu treatment in children

Genentech, part of the Roche Group, yesterday announced promising phase 3 trial findings for the use of one-dose baloxavir marboxil (Xofluza) to safely treat flu in children, according to results presented on Sep 1 during the Options X Congress in Singapore.

Baloxavir, developed in Japan, is the newest novel flu treatment since oseltamivir and zanamivir and was approved by the US Food and Drug Administration (FDA) in October 2018 for use in patients ages 12 years and older.

The recent global trial was designed to assess tolerability and effectiveness in healthy children ages 1 through 11 years old, Genentech said in a press release. The one-dose treatment was administered as an oral suspension, and researchers evaluated patients up to study day 29.

Regarding adverse events, findings were consistent with baloxavir's known safety profile. Of kids in the trial who received baloxavir, 46.1% had at least one treatment-related adverse event compared to 53.4% of those in the oseltamivir arm. Efficacy findings were similar to that of oseltamivir. And similar to findings in adults and adolescents, baloxavir shortened flu virus shedding by more than 2 days compared to oseltamivir. The median time was 24.2 hours compared to 75.8 hours. The time to alleviation of flu symptoms was a median 138.1 hours for baloxavir, compared to 150 hours for oseltamivir.

Sandra Horning, MD, chief medical officer and health of global product development for Genentech, said in the statement that each year one in three children develop flu, and their less mature immune systems mean they are slower to fight infection and are more susceptible to complications. "We are committed to developing new, more convenient treatment options for children with the flu and look forward to sharing these data with global health authorities."

Researchers are currently conducting phase 3 trials in other populations including children younger than 1 year and people hospitalized with severe flu. Teams are also assessing the drug for prophylactic use.
Sep 2 Genentech press release


Emergent BioSolutions awarded contract for stockpile smallpox vaccine

Emergent BioSolutions today announced that it was awarded a contract worth about $2 billion over the next 10 years to deliver the ACAM200 smallpox vaccine to the US government's Strategic National Stockpile.

In a statement, the company said the contract was awarded by the US Department of Health and Human Services' Assistant Secretary for Preparedness and Response (ASPR), and that  the number of doses depends on timing and tiered-pricing terms that are subject to ASPR discretion. ACAM2000 is the only vaccine licensed by the FDA for active immunization against smallpox for those at high risk for infection.

In early 2018, Emergent BioSolutions received a contract worth $26 million to supply the smallpox vaccine complications therapy vaccinia immune globulin intravenous (VIGIV) to the US government.

For the ACAM2000 vaccine, the contract consists of a 1-year base period of performance, worth about $170 million, and 9 option years. The company said it expects to deliver the majority of the doses to the SNS under the base year by the end of 2019. The multiple-year contract is designed to replace the current vaccine stockpile and comes at the end of a 10-year $425 million contract to establish domestic manufacturing and procurement. The one-dose vaccine is the primary vaccine the government would use in the event of a smallpox emergency.
Sep 3 Emergent BioSolutions press release
Mar 2, 2018, CIDRAP News scan "
Emergent awarded $26 million for vaccinia immune globulin treatment"


Liberia declares Lassa health emergency

Liberia health officials yesterday declared a health emergency due to a Lassa fever outbreak that has affected four counties and resulted in 21 deaths so far this year, according to media reports.

At a media briefing, Francis Kateh, MD, the country's chief medical officer, said officials are worried about infections in health workers and that a lab technician is also among the people who have died, Xinhua, China's state news agency, reported yesterday.

Affected counties include Nimba, Grand Bassa, Bong, and Grand Cru. Officials said another cause for concern is that cases are expending outside an area already identified as the "Lassa belt".

The World Health Organization (WHO) regional office for Africa said in its weekly outbreaks and health emergencies report that Liberia has recorded 34 cases as of Aug 25, 25 of them confirmed and 9 of them fatal. It notes that there are 92 suspected cases, 21 of those fatal. It said the three most recent cases were from Bong County, including that of the lab technician, whose exposure is under investigation.

In West Africa, Lassa virus—which can cause a viral hemorrhagic illness in humans—is typically spread by contact with urine or feces of African soft-furred rats. The virus can spread from person to person through contact with body fluids. The virus sickens about 100,000 to 300,000 people in Africa each year, about 5,000 of them fatally. No vaccine is available, though global health groups have prioritized the disease for vaccine development.
Sep 2 Xinhua story

H5N1 avian flu outbreak reported at Nepalese poultry farm

Nepal's agriculture ministry yesterday reported a highly pathogenic H5N1 avian influenza outbreak at a farm in Koshi zone in the eastern part of the country, according to a notification from the World Organization for Animal Health (OIE).

The outbreak began on Aug 19 at a facility housing mixed poultry, including turkeys, backyard chickens, ducks, and quail of different ages. The virus killed 195 of 417 susceptible birds. Authorities culled the remaining 222 birds. The team also destroyed feed ingredients. The event was declared as resolved yesterday.

Nepal's last H5N1 outbreak, which struck backyard birds in Bagmati zone, was reported in June.
Sep 2 OIE report on H5N1 in Nepal

Stewardship / Resistance Scan for Sep 03, 2019

News brief

CARB-X to fund Group A Strep vaccine candidate

CARB-X today announced an award of more than $1.6 million to biopharmaceutical company SutroVax of Foster City, Calif., to develop a vaccine to prevent infections caused by Group A Streptococcus.

The Group A Streptococcus (GAS) bacterium can cause a variety of infections that range from minor illnesses such as pharyngitis (strep throat)—a major source of antibiotic prescriptions worldwide—to more severe and deadly infections like necrotizing fasciitis. It can also cause post-infectious immune-mediated rheumatic heart disease, which is a leading cause of mortality in the developing world. There is currently no vaccine for GAS. 

According to a press release from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), SutroVax's vaccine candidate consists of a GAS carbohydrate antigen combined with an immunogenic protein carrier, and has been modified to avoid triggering an immune response that can adversely affect human cardiac or brain tissue.

"The SutroVax project is in the early stages of development but if successful and approved for use in patients, it could save lives, improve public health and strengthen health security worldwide," said CARB-X executive director Kevin Outterson, JD.

SutroVax could receive an addition $13.4 million in funding if certain project milestones are met.
Sep 3 CARB-X press release


Study highlights drawbacks of pre-operative urine testing

A study by Boston-area researchers indicates pre-operative urine screening and identification of pyuria increases antibiotic exposure but does not improve post-operative outcomes.

In the study, which was published in Clinical Infectious Diseases, researchers from the Veterans Administration (VA) Boston Healthcare System, Boston University School of Medicine, and Harvard Medical School analyzed a cohort of pre-operative patients within the national VA system who had a urinalysis performed during the 30-day pre-operative period. The primary exposure of interest was the presence of pyuria, which is frequently treated with antibiotics, even when patients are asymptomatic. The primary outcome was antibiotic initiation. Secondary outcomes included post-operative surgical site infections (SSIs), urinary tract infections (UTIs), and Clostridioides difficile infections.

Of the 70,277 patients who underwent surgical procedures at the VA during the study period (October 2008 through September 2013), 41,373 patients had a urinalysis performed in the 30-day window prior to surgery, and 3,617 had varying degrees of pyuria detected (43.8% low, 21.9% moderate, and 34% high). In patients with any degree of pyuria, 887 (24.5%) received antimicrobials, and the odds of receiving antimicrobials increased as the degree of pyuria increased (low pyuria, 14.7%, moderate pyuria, 24.0%, high pyuria, 37.4%).

Pre-operative pyuria was associated with post-operative C difficile infections (adjusted odds ratio [aOR], 1.7; 95% confidence interval [CI], 1.2 to 2.4), but the risk was higher in patients who received antimicrobials (aOR 2.4; 95% CI, 1.7 to 3.4). Pyuria was not associated with SSI but was associated with increases in UTI after orthopedic (aOR, 1.5; 95%, 1.1 to 2.1) and vascular procedures (aOR, 2.5; 95% CI, 1.4 to 4.5). However, antimicrobial therapy did not significantly change this association.

The researchers say the study highlights the importance of diagnostic stewardship and avoiding low-value tests.

"These findings underscore the need to avoid testing in asymptomatic patients to reduce unnecessary and excessive antimicrobial treatment in patients who will not benefit from the intervention," the authors of the study write. "Once something is seen in clinical medicine, it cannot be unseen; thus, the best strategy is to not perform tests that do not have a clinical indication."
Aug 30 Clin Infect Dis abstract


More ASP training for medical residents linked to better prescribing

A study conducted at a small community teaching hospital in Michigan has found that adding antibiotic stewardship-focused educational training sessions for medical residents was associated with better adherence to antibiotic prescribing guidelines, researchers reported yesterday in Infection Control and Hospital Epidemiology.

The retrospective cohort study looked at antibiotic prescribing practices for three common infections (pneumonia, cellulitis, and UTI) among three physician services at the hospital—the family medicine (FM) resident service, the internal medicine (IM) resident service, and the hospitalist service. While all three services receive daily audit and feedback on antibiotic prescribing and baseline antimicrobial stewardship program (ASP) training, the FM residents also receive bi-weekly stewardship-focused rounding and education sessions with an ASP physician and a clinical pharmacist. The aim of the study was to compare guideline-concordant therapy among the three groups, based on the hospital's ASP guidelines.

Of 1,572 patients discharged from the hospital from July 2016 through June 2017 with diagnoses of pneumonia, cellulitis, or UTI, 295 were eligible for inclusion; 96 were treated by the FM group, 69 by the IM group, and 130 by the hospitalist group. The percentage of patients receiving guideline-concordant antibiotic selection empirically was similar between groups for all diagnoses (FM, 87.5%; IM, 87%; hospitalist, 83.8%; P = .702), and no differences were observed in appropriate definitive antibiotic selection among groups (FM, 92.4%; IM, 89.1%; hospitalist, 89.9%; P = .746). But the FM resident service was more likely to prescribe a guideline-concordant duration of therapy across all diagnoses (FM, 74%; IM, 56.5%; hospitalist, 44.6%; P < .001). 

"The FM team overall prescribed more appropriate durations of therapy than the IM and hospitalist services when all disease states were considered, which may reflect the added benefit of consistent biweekly presence of the ASP team during patient care rounds on top of routine audit and feedback," the authors of the study write. "These results suggest that more frequent and multifaceted interactions with the ASP team may positively impact guideline-concordant prescribing habits."
Sep 2 Infect Control Hosp Epidemiol abstract

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