Stewardship / Resistance Scan for Feb 06, 2019

News brief

FDA to review new treatments for urinary tract infections, pneumonia

Merck announced yesterday that the US Food and Drug Administration has accepted for priority review a New Drug Application (NDA) for the combination of relebactam and imipenem/cilastatin and a supplemental NDA for Zerbaxa (ceftolozane and tazobactam).

Merck is seeking approval for the combination of relebactam, an investigational beta-lactamase inhibitor, with imipenem/cilastatin to treat complicated urinary tract infections (cUTIs) and complicated intra-abdominal infections caused by certain susceptible gram-negative bacteria in adults with limited or no alternative therapies available. The supplemental NDA for Zerbaxa, which is already approved for patients with cUTIs, is to treat adults with nosocomial pneumonia, including ventilator-associated pneumonia, caused by certain susceptible gram-negative organisms.

"There is a major unmet need for new treatment options to address the growing danger of serious and potentially life-threatening infections caused by gram-negative bacteria," Nicholas Kartsonis, MD, senior vice president and head of clinical research for infectious diseases and vaccines at Merck, said in a press release. "In a space where there are currently very few treatment options, these filings underscore Merck's ongoing commitment to delivering new antibacterial agents to healthcare practitioners and patients."

Corresponding applications for both medicines have been filed with the European Medicines Agency.
Feb 5 Merck press release

CARB-X grant focuses on gram-negative superbugs

Today the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator, also known as CARB-X, announced an award of $4.4 million to Recida Therapeutics of Menlo Park, Calif., to develop a novel antibiotic targeting gram-negative superbugs.

"The world urgently needs new classes of antibiotics and other life-saving products to prevent, diagnose, and treat deadly infections," said Kevin Outterson, JD, executive director of CARB-X and a Boston University law professor, in a press release. "Recida's lead program inhibits LpxC, and would represent a new drug class against gram-negative superbugs, if approved by the FDA. The projects in the Powered by CARB-X portfolio are in early development, but if successful, they offer tremendous hope in the global fight against drug-resistant bacteria."

The money will help Recida prepare their drug, RC-01, for an Investigational New Drug (IND) application submitted to the US Food and Drug Administration (FDA). In preclinical testing, RC-01 inhibited LpxC, a key enzyme in the outer membrane of gram-negative bacteria, including Enterobacteriaceae and Pseudomonas aeruginosa.

Recida's RC-01 is 1 of 12 new antibiotics in CARB-X's portfolio. Established in 2016, CARB-X will invest $500 million in antibacterial research and development over a 5-year span.
Feb 6 CARB-X press release

Educational intervention in China cuts prescribing for kids' respiratory infections

Chinese, Canadian, and British researchers report that an educational intervention to reduce antibiotic prescribing in children with upper respiratory tract infections (URTIs) significantly cut the prescribing rate in rural Chinese primary care facilities. The study appeared yesterday in PLOS Medicine.

The study was a long-term follow-up to an unblinded cluster-randomized controlled trial of 25 primary care facilities in two counties in rural China. That study found that the intervention, which included clinical guidelines, monthly prescriber-review meetings, doctor-patient communication skills training, and educational materials for caregivers, reduced the antibiotic prescribing rate among children aged 2 to 14 with URTIs by 29 percentage points from the baseline within 6 months.

In the long-term follow-up, the researchers looked at trial outcomes in the 14 facilities (7 intervention facilities and 7 control facilities) in one county at 18 months after the start of the intervention (12 months after the trial ended) and conducted interviews to understand how the interventions were sustained. After adjusting for patient and prescriber covariates, they found that, compared to the non-intervention facilities, the antibiotic prescribing rate in the intervention facilities was 36 percentage points lower than it was at baseline.

Providers at two of the intervention facilities reported better clinical knowledge in appropriate use of antibiotics, enhanced communication skills with patients and caregivers, and increased confidence in not prescribing antibiotics for common URTIs, even when requested. In addition, better-performing facilities reported more frequent peer-review meetings.

Though the authors say they would not expect the improvement in antibiotic prescribing to be sustained for longer time periods without refresher training sessions and regular supervision and monitoring, they believe this type of intervention could be successful in other low- and middle-income countries, where roughly 80% of URTIs are treated with antibiotics.
Feb 5 PLOS Med study

News Scan for Feb 06, 2019

News brief

MERS sickens three more in Saudi Arabia

Saudi Arabia's health ministry today reported three more MERS-CoV cases, two of them linked to ongoing outbreak activity in Wadi ad-Dawasir in the south-central part of the country.

Over the past several days, the country has reported 12 Middle East respiratory coronavirus (MERS-CoV) cases from Wadi ad-Dawasir, some involving secondary healthcare- and household-related exposure. Today's new cases from the city are a 33-year-old man who had household exposure and a 23-year-old man who had healthcare exposure. Both men are hospitalized for their infections.

The third new infection was reported in a 67-year-old man from Khamis Mushait in Asir province in southwestern Saudi Arabia. He wasn't exposed to camels or another known case-patient before he became ill, and he is hospitalized.

Saudi Arabia has reported a steady stream of MERS-CoV cases in 2019, with 27 reported so far.
Saudi MOH epi week 6 report

Rare H1N2 flu reassortant reported in Swedish adult

Sweden on Jan 25 reported a human influenza H1N2 infection, which appears to be a reassortant of the seasonal influenza A strains 2009 H1N1 and H3N2, the US Centers for Disease Control and Prevention said in a Feb 3 notice. The World Health Organization (WHO) first noted the case on its European regional flu surveillance site.

According to a weekly update from FluNewsEurope, the regional monitoring system, the virus was detected in a sample collected at the end of December in an adult. A Swedish government report cited in the update said the sample was collected in southern Sweden.

The CDC said genetic analysis shows that the Swedish H1N2 reassortant has an H1 hemagglutinin gene similar to seasonal 2009 H1N1 and an N2 neuraminidase gene similar to seasonal H3N2. In its risk assessment, the CDC said the health risk is likely similar to other seasonal flu viruses, that it hasn't been detected in anyone beyond the one patient, and that current seasonal vaccines would likely protect against the virus. Testing shows no markers linked to resistance to neuraminidase inhibitor antiviral medications.

Other H1N2 reassortants have appeared in the past, but have been rare. The Swedish detection is the second involving reassortment between 2009 H1N1 and H3N2. The first was reported in 2018 in the Netherlands and involved a young child who had a mild illness. Ferret experiments with the virus suggested that it had limited capacity for human-to-human spread.
Feb 3 CDC update
Jan 25 FluNewsEurope report
Mar 23, 2018, CIDRAP News scan "Dutch officials reports reassortant seasonal flu H1N2 infection"

WHO: Flu activity slows in North America, picks up in Europe

In the latest global flu update, the World Health Organization (WHO) said flu activity has slowed slightly in North America, but picked up in Europe and North Africa.

"In the United States of America, influenza activity appeared to have plateaued, with detections of mainly influenza A (H1N1)pdm09 virus followed by influenza A(H3N2) viruses," the WHO said. "Influenza like illness (ILI) activity continued to be reported above the national baseline and influenza-confirmed hospitalization rates were lower than previous seasons."

Influenza A is still the dominant strain of the 2018-2019 flu season. H1N1 is the dominant subtype in North America, North Africa, and East Asia. Europe has reported both H1N1 and H3N2 circulating at similar proportions, while H3N2 has been the dominant subtype in Southern Asia and Iran.

Data collected from national influenza laboratories between Jan 7 and Jan 20 showed that 98.3% of positive flu samples were typed as influenza A and 11.7% as influenza B. Of the subtyped influenza A viruses, 77.7% were influenza 2009 H1N1 and 22.3% were H3N2.
Feb 6 WHO update

H5N8 avian flu strikes birds in Iran and Kuwait

In the latest avian influenza developments, two Middle East countries—Iran and Kuwait—reported new outbreaks involving highly pathogenic H5N8, according to separate reports from the World Organization for Animal Health (OIE).

Iran reported two new outbreaks in poultry, part of a small but steady stream of detections that began in early January. One of the new events began Jan 25 in backyard poultry in Gilan province, killing 24 of 315 susceptible birds. The other started on Jan 26 in backyard poultry in West Azarbayejan province, killing 7 of 190 birds. In both instances, the surviving birds were culled and the outbreaks are classified as resolved. Gilan and West Azarbayejan province are both located in northwestern Iran.

Meanwhile, Kuwait's agriculture ministry today reported an H5N8 outbreak in captive wild birds at a live bird market in Al Farwaniyah governorate in the east-central part of the country. The outbreak began on Jan 24, with the virus killing 3 of 2,000 birds. The remaining ones were culled as part of the outbreak response, which also included market closure, movement restriction, and a ban on the export of live birds. According to the OIE report, there are no commercial farms within 10 km of the facility, and intensive surveillance is under way at poultry farms, in backyard birds, other bird markets, and in migratory birds.

Kuwait's last H5N8 outbreak occurred in December 2016.
Feb 5 OIE report on H5N8 in Iran
Feb 6 OIE report on H5N8 in Kuwait