ASP News Scan for Jul 22, 2016

News brief

WHO ranks antibiotics for stewardship efforts

Originally published Jul 21.

Carbapenems, penicillins, quinolones, macrolides and ketolides, and the newest cephalosporins were among the antibiotics that a World Health Organization (WHO) expert panel yesterday rated as "critically important" for human medicine of highest priority in limiting their use in food animals to combat resistance to the drugs.

The WHO advisory group's latest update of the list appeared in Clinical Infectious Diseases. It was first developed in 2005 and updated about every 2 year since then, most recently in 2013.

"The updated ranking allows stakeholders in the agriculture sector and regulatory agencies to focus risk management efforts on drugs used in food animals that are the most important to human medicine," the authors said.

"In particular, the current large scale use of fluoroquinolones, macrolides, third generation cephalosporins and any potential use of glycopeptides and carbapenems needs to be addressed urgently."

The complete list of antibiotics deemed critical to human health is: aminoglycosides, ansamycins, carbapenems and other penems, third- and fourth-generation cephalosporins, phosphonic acid derivatives, glycopeptides, glycylcyclines, lipopeptides, macrolides and ketolides, monobactams, oxazolidinones, penicillins (natural, aminopenicillins, and antipseudomonal), polymyxins, quinolones, and drugs solely used to treat tuberculosis and other mycobacterial diseases.

Phosphonic acid derivatives, monobactams, and polymyxins are new to the list because of their greater importance for treating multi-resistant gram-negative bacteria. Streptogramins, on the other hand, were bumped from the critically important list to the next level—highly important—because more effective antimicrobials with fewer side effects are now available to treat gram-positive infections, the experts said.
Jul 20 Clin Infect Dis abstract


New antibiotic performs well against hospital pneumonia in phase 3 trial

Originally published Jul 21.

London-based drug company AstraZeneca today announced that Zavicefta, its new combination antibiotic for treating a spectrum of serious gram-negative infections, performed well in a phase 3 trial against hospital-acquired pneumonia (HAP), including infections tied to ventilator use.

The intravenous drug is a combination of third-generation cephalosporin drug ceftazidime and the broad-spectrum beta-lactamase inhibitor avibactam. It was found to be statistically non-inferior to meropenem, a carbapenem antibiotic, in the REPROVE trial, which involved 879 HAP patients in 23 countries, the company said in a news release. Results were comparable between the two drugs for both cure rates at 21 days and all-cause mortality at 28 days.

Safety profiles were similar for both Zavicefta and meropenem. Full results from the REPROVE trial are expected to be presented at future scientific meetings, the company said.

Hans Sijbesma, managing director of AstraZeneca's Antibiotics Business Unit, said, "The positive results from this important phase 3 trial validate our science-led approach and confirm the effectiveness of Zavicefta in treating hospital-acquired pneumonia, providing patients and physicians with a much-needed new treatment option in the fight against antibiotic-resistant pathogens."

The European Commission approved the drug on Jun 24 for intravenous use in treating adults who have HAP.
Jul 21 AstraZeneca press release


Algorithm may help identify drugs to treat resistant fungal infections

Originally published Jul 14.

A team of Chinese scientists has developed an algorithm that can identify drug combinations to treat drug-resistant fungal infections.

In a study published today in PLoS Computational Biology, the researchers report that they have developed a novel algorithm—called Network-based Laplacian regularized Least Square Synergistic (NLLSS) drug combination prediction—that successfully identified 7 of 13 synergistic drug combinations to treat the fungal pathogen Candida albicans. The algorithm, which was experimentally confirmed, works by integrating different kinds of information such as known synergistic drug combinations, drug-target interactions, and drug chemical structures.

According to the study, fungal infections are one of the leading causes of hospital-acquired infections and are associated with high mortality, especially in patients with weakened immune systems. Moreover, drug resistance is becoming increasingly common in fungal infections. But synergistic drug combinations—in which the combination of two agents increases the effectiveness of a drug—have become a promising avenue of treatment for drug-resistant infections, the authors said.

The problem, however, is that effective drug combinations have traditionally been identified through screening all possible combinations of a pre-defined set of drugs, which is a timely, costly, and labor-intensive process. Developing an algorithm that can computationally screen and identify synergistic drug combinations to treat drug-resistant fungal infections, the authors said, could save time and money and provide new treatments for overcoming fungal resistance.
Jul 14 PLoS Comput Biol study

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Flu Scan for Jul 22, 2016

News brief

Study: Prime-boost H5 vaccination strategy could help in pandemic

A dose of H5 avian influenza vaccine may set the stage for a stronger cellular immune response if a person later encounters a different strain of H5 virus, which suggests that this prime-boost strategy could be useful in fighting an H5N1 pandemic, according to a study reported Jul 20 in the Journal of Infectious Diseases.

The researchers, from several US institutions, looked at the effect of the prime-boost vaccine strategy on CD4+ and CD8+ T cell responses. They said T cells can recognize epitopes (components of antigens) shared by many different flu viruses and that T cells in mice provide protection against a wide range of influenza A viruses.

The study involved 517 healthy adults who had participated in any of nine earlier studies involving vaccination with a clade 1 H5 virus, a 2004 strain from in Vietnam. The volunteers had received two or three clade 1 vaccine doses between 1 and 6 months apart, with or without an adjuvant. A subset of participants was given a placebo.

In the new study, those who had received the clade 1 vaccine were randomly assigned to get a single dose of either 15 or 90 micrograms (mcg) of a vaccine based on an H5 clade 2 virus, a 2005 strain from Indonesia. The placebo recipients from the earlier trials received two doses (15 or 90 mcg) of the clade 2 vaccine, a month apart. The doses were given 2 to 3 years after the priming doses.

The team reported that those who had been primed with the clade 1 vaccine showed "significantly enhanced" cross-reactive T cell responses to the clade 2 vaccine 6 months after vaccination, compared with the placebo recipients. The amount of priming dose (15 or 90 mcg) had no effect on the magnitude of the T cell responses to the clade 2 vaccine, but the magnitude and duration of T cell responses were significantly lower in volunteers age 65 years and older.

The presence of adjuvant in the priming vaccine also was found to have a positive effect on T cell responses to the clade 2 vaccine, but it was weaker than the effect of age.

"H5 heterotypic priming prior to onset of an H5N1 pandemic may increase magnitude and duration of immunity against a newly drifted pandemic H5 virus," the authors said. But they cautioned that the true importance of the cross-reactive T cell responses can be determined only in phase 3 efficacy studies designed to look for correlations between those responses and actual protection against flu.
Jul 20 J Infect Dis abstract


Taiwan reports 3 H5N8 avian flu outbreaks in poultry

The World Organization for Animal Health (OIE) today reported details on three outbreaks of highly pathogenic H5N8 avian flu outbreaks in Taiwan. The outbreaks occurred in late June and early July and involved 2,874 birds. The source of the outbreaks is unknown at this time.

The first outbreak occurred on Jun 23 in the Wanhua district of Taipei City, and involved 103 native chickens found in a small farm's slaughterhouse. The second outbreak was on Jul 1 in the Xinhua district of Tanian City, and resulted in the death or culling of 2,230 geese. The final outbreak was reported on Jul 3 in Fangshan district, Kaohsiung City, and involved 541 slaughterhouse chickens.

The OIE said neighboring farms are being closely monitored, and weekly follow-up reports will be published.
Jul 22 OIE report

News Scan for Jul 22, 2016

News brief

Yellow fever declining in Angola; DRC lab problems slow case confirmation

The rate of new suspected and confirmed cases of yellow fever continues to decline in Angola, but health officials are concerned about disease activity in Benguela province, where surveillance gaps and reporting delays are occurring, the World Health Organization (WHO) said yesterday in its weekly update.

Angola reported 57 new cases this week, bringing its outbreak total to 3,682 suspected cases, of which 877 are confirmed. Last week the country had 73 new cases.

Mass vaccination campaigns that began in Luanda have now reached most other affected areas, with a recent focus on border areas, the agency added.

Recent yellow fever patterns in the Democratic Republic of the Congo (DRC) are less clear, because technical problems at the national lab have hampered case confirmation for the past 4 weeks, though corrective actions are underway, according to the report. There's a backlog of at least 300 suspected cases, including one from Kasai province, which hasn't previously reported a case. Surveillance and vaccination efforts have focused on affected zones of Kinshasa and Kongo Central, with reactive immunization campaigns that launched on Jul 20.

In other countries that have reported yellow fever cases over the past few months, the situations haven't changed much, the WHO said, noting that disease activity is stable in Brazil, Chad, Ghana, Guinea, Republic of Congo, and Uganda.
Jul 21 WHO yellow fever situation report


Saudi Arabia confirms new MERS case in Buraydah

Saudi Arabia's Ministry of Health (MOH) reported another MERS-CoV case today, this time in the city of Buraydah. The case is not linked to the current outbreak tied to the King Khalid University Hospital in Riyadh, or to a recent cluster of cases in Najran.

The 27-year-old man, an expatriate, is in critical condition. He presented with symptoms of MERS-CoV (Middle East respiratory syndrome coronavirus), and the MOH said he had primary exposure to the virus, meaning not from another patient. The man is not a healthcare professional.

The new case brings Saudi Arabia's MERS-CoV total to 1,440, including 606 deaths, since 2012.
Jul 22 MOH report


Kapowsin Meats recalls 11,000 pounds of pork over Salmonella outbreak

Yesterday the US Department of Agriculture's Food Safety and Inspection Service (FSIS) announced in a news release that Kapowsin Meats recalled 11,658 pounds of pork products that may be contaminated with Salmonella.

The company's boxed and bagged "Whole Hogs for Barbecue" have been linked to an outbreak of Salmonella infections.

FSIS was first notified of a possible Salmonella infection on Jul 13. By Jul 19, the FSIS, working with the Washington State Department of Health, confirmed that at least 3 cases of salmonellosis were probably linked to whole hogs from Kapowsin Meats, a Washington state–based company. According to FSIS, people reported consuming the hogs from Jul 5 to Jul 7.

FSIS and Kapowsin Meats are concerned people may have hogs stored in their freezers, and FSIS included an image of the product label with the news release to guide consumers.

"Consumers who have purchased these products are urged not to consume them," the statement said. "These products should be thrown away or returned to the place of purchase."
Jul 21 FSIS release

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