Japan approves new one-dose antiviral flu drug

Japan's health ministry has given fast-track approval to a new flu antiviral with a different mechanism of action than neuraminidase inhibitors that offers a one-dose treatment option, the Wall Street Journal reported today.

The drug—from Shionogi, based in Osaka—is called Xofluza (baloxavir marboxil) and is an endonuclease inhibitor designed to prevent viral replication by inhibiting cap-dependent endonuclease activity of the viral polymerase, a process known as "cap snatching."

According to the report, trials in Japan and the United States found that the drug could wipe out the virus in a median time of 24 hours, three times faster than oseltamivir (Tamiflu). Both drugs, however, took the same amount of time to curb flu symptoms.

Roche has teamed up with Shionogi to license the drug outside of Japan, including in the United States. Another late-stage trial is wrapping up in Japan and the United States, after which the company hopes to file for US Food and Drug Administration (FDA) approval later this year.

In Japan, the drug probably won't be available until May, because the company is still waiting for insurers to set a price.
Feb 23 Wall Street Journal story

 

UK groups announce Zika vaccine collaboration

The University of Liverpool yesterday announced a new UK collaboration to develop a Zika vaccine that can be used during pregnancy. The project is supported by a £4.7million ($6.5 million) grant from the UK Department of Health and Social Care and managed by Innovate UK, according to a University of Liverpool news release.

The goal of the project is to take two vaccine candidates to trials in humans within the next 3 years. With researchers from the University of Manchester, Public Health England, and the pharmaceutical companies, the group plans to confirm the safety of two new vaccine candidates that are based on a safe version of an existing smallpox vaccine before advancing to the first human trials at the Royal Liverpool University Hospital Clinical Research Unit.

According to a profile for the vaccine, scientists are taking a "twin track" in which the vaccine candidate would produce antibody and killer T cells to prompt better and long-lasting immunity.

Neil French, PhD, director of the Center for Global Vaccine Research at the University of Liverpool, said in the release, "Although the current Zika outbreak has slowed, there remains a significant risk of foetal abnormality when pregnant mothers become infected, and the changing climate raises the possibility of major epidemics occurring in previously unaffected parts of the world. A ready to use vaccine would dramatically reduce the threat that we face from Zika."
Feb 22 University of Liverpool press release

 

OIE avian flu snapshot notes number, diversity, spread of latest outbreaks

In its latest epidemiologic update on avian influenza, the World Organization for Animal Health (OIE) said that the highly pathogenic avian flu situation in the second panzootic wave, under way since 2013, is notable. Factors include a substantial number of countries and territories affected by outbreaks in domestic birds, a substantial number of outbreaks, and circulation of diverse ubtypes, which has added complexity to control and eradication.

In January of 2018, eight countries (Afghanistan, Cambodia, Taiwan, Iraq, Japan, South Korea, Saudi Arabia, and South Africa) and two of the world's regions (Africa and Asia) were affected by outbreaks in poultry.

Compared with the first panzootic that took place from 2005 through 2012, the current panzootic is marked by triple the number of circulating avian flu subtypes (12 vs. 4). In the current panzootic, nearly 120 million birds were lost through disease and culling, and all regions of the world have been affected, with 68 countries reporting at least one outbreak. H5N1, H5N2, and H5N8 have been the most common strains.

Most recently, new and recurring outbreaks of H5N1, H5N8, and H5N6 have struck Asia, Europe, and the Middle East, with signs that the geographic distribution is increasing. From a public health perspective, H7N9, H5N6, and H5N1 post the greatest threats to humans.
Jan 25 OIE situation update

In outbreak developments, Taiwan today reported four more highly pathogenic H5N2 outbreaks in poultry, three on farms and one detected at a slaughter house, according to a separate report from the OIE.

The events began on Feb 11 and Feb 12, striking locations in Taichung City, as well as Chiayi, Pingtung, and Yunlin counties. Affected species included native chickens and breeding geese. Taken together, the outbreaks killed 1,321 of 30,767 susceptible birds, and the rest were destroyed as part of response steps.
Feb 23 OIE report on H5N2 in Taiwan

 

Brazil proposes vaccinating entire country against yellow fever

Yesterday Ricardo Barros, the Brazilian minister of health, proposed the entire country be vaccinated against yellow fever in an effort to control the largest outbreak of the flavivirus seen in South America in decades, Xinhua, China's state news agency, reported.

Currently, the government is focusing its vaccination efforts on the country's most populous states, Rio de Janeiro and Sao Paulo. Those states, along with Minas Gerais, have had by far the most yellow fever cases in the last year. But efforts to vaccinate citizens of those states have fallen short, with only about 20% of people receiving a full or fractioned dose of the vaccine.

Libbs Farmaceutica in Sao Paulo is set to begin monthly production of 4 million doses of yellow fever vaccine, the story said. Fractioned doses, one-fifth the standard dose, are being used in an effort to reach as many people as possible.

About 34 million Brazilians live in states in the northeast and southern part of the country not yet affected by yellow fever. Last week, Brazil's Ministry of Health confirmed 941 human cases of yellow fever since Jul 1, 2016, which includes 284 deaths.
Feb 22 Xinhua story

 

Report says resilient communities key to disaster preparedness

A new report from the Johns Hopkins Center for Health Security said that while America is well prepared to handle small health emergencies (think tornadoes), it is poorly equipped to handle large-scale natural disasters or complex health events, including the next pandemic.

The report, "A Framework for Healthcare Disaster Resilience: A View to the Future," was released yesterday at an event at the National Press Club in Washington, D.C. The authors said focusing on strengthening existing community healthcare coalitions and resilience is the best way to prepare America for complex and large-scale health events, from catastrophic weather to bioterrorism.

"It is now widely recognized that resilience of communities and systems should be the goal rather than just preparedness," the authors wrote in the report. "Resilient communities seek to resist the impact of disasters, recover promptly to normal operational capacity, and learn how better to withstand future events."

The authors make four recommendations for strengthening resilience: launching a federal program that provides incentives for community organizations to become involved in health sector preparedness, creating centers of disaster resource hospitals based on geographic location, supporting healthcare collations, and designating a federal coordinator for catastrophic health event preparedness.
Feb 22 Center for Health Security press release

Stewardship / Resistance Scan for Feb 23, 2018

News brief

Belgian study reports high rate of improper antibiotic prescribing in kids

Belgian researchers report that almost a third of prescriptions for fluoroquinolones written for hospitalized children were deemed inappropriate, according to a study today in BMC Infectious Diseases.

The investigators analyzed data on all 262 fluoroquinolone prescriptions from 2010 through 2013 at two university children's hospitals. They then employed univariate and multivariate logistic regression models to analyze risk factors for inadequate dosing.

The team found that 79 prescriptions (30.2%) were inappropriate, with 57.0% of improper prescribing classified as underdiagnosing. Only 16.8% of the drugs were prescribed for labeled indications, and only 35.1% were guided by bacteriologic findings. Infants and older preschoolers were at particular risk for dosing errors.

The authors conclude, "[Fluoroquinolone] prescriptions for children should be improved by specific pediatric antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should optimise dosing recommendations for children."
Feb 23 BMC Infect Dis study

 

Researchers note high rate of extremely resistant Pseudomonas in Thailand

Among 255 patients with Pseudomonas aeruginosa infections, 56 (22.0%) had extensively drug-resistant P aeruginosa (XDR-PA) and 32 (12.5%) had the multidrug-resistant (MDR-PA) form, scientists from Thailand announced yesterday in PLoS One.

The investigators retrospectively studied patients hospitalized with PA infections from April to December of 2014. The combined XDR-PA and MDR-PA total represents a 34.5% incidence of drug resistance. The researchers said that receiving total parenteral nutrition, prior carbapenem use, and prior fluoroquinolone use were all associated with a higher rate of XDR-PA. Factors associated with mortality among all patients were sepsis or septic shock, admission to a medical department, receiving a central venous catheter, and having an XDR-PA infection.

The authors reported that all XDR-PA infections remained susceptible to colistin. They conclude, "The prompt administration of an appropriate empirical antibiotic should be considered when an XDR-PA infection is suspected."
Feb 22 PLoS One study

ASP Scan (Weekly) for Feb 23, 2018

News brief

Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Belgian study reports high rate of improper antibiotic prescribing in kids

Belgian researchers report that almost a third of prescriptions for fluoroquinolones written for hospitalized children were deemed inappropriate, according to a study today in BMC Infectious Diseases.

The investigators analyzed data on all 262 fluoroquinolone prescriptions from 2010 through 2013 at two university children's hospitals. They then employed univariate and multivariate logistic regression models to analyze risk factors for inadequate dosing.

The team found that 79 prescriptions (30.2%) were inappropriate, with 57.0% of improper prescribing classified as underdiagnosing. Only 16.8% of the drugs were prescribed for labeled indications, and only 35.1% were guided by bacteriologic findings. Infants and older preschoolers were at particular risk for dosing errors.

The authors conclude, "[Fluoroquinolone] prescriptions for children should be improved by specific pediatric antimicrobial stewardship teams. Furthermore, pharmacokinetic studies should optimise dosing recommendations for children."
Feb 23 BMC Infect Dis study

 

Researchers note high rate of extremely resistant Pseudomonas in Thailand

Among 255 patients with Pseudomonas aeruginosa infections, 56 (22.0%) had extensively drug-resistant P aeruginosa (XDR-PA) and 32 (12.5%) had the multidrug-resistant (MDR-PA) form, scientists from Thailand announced yesterday in PLoS One.

The investigators retrospectively studied patients hospitalized with PA infections from April to December of 2014. The combined XDR-PA and MDR-PA total represents a 34.5% incidence of drug resistance. The researchers said that receiving total parenteral nutrition, prior carbapenem use, and prior fluoroquinolone use were all associated with a higher rate of XDR-PA. Factors associated with mortality among all patients were sepsis or septic shock, admission to a medical department, receiving a central venous catheter, and having an XDR-PA infection.

The authors reported that all XDR-PA infections remained susceptible to colistin. They conclude, "The prompt administration of an appropriate empirical antibiotic should be considered when an XDR-PA infection is suspected."
Feb 22 PLoS One study

 

Study evaluates cost-effectiveness of Clostridium difficile treatments

Originally published by CIDRAP News Feb 22

A systematic review of treatments for Clostridium difficile infection (CDI) yesterday in Infection Control and Hospital Epidemiology concludes that the most cost-effective treatment remains unclear.

The literature review conducted by researchers from the Cleveland Clinic and the University of Texas School of Public Health included 14 studies on economic valuations of various treatment modalities for initial and recurrent CDI. Thirteen of the studies were conducted in high-income countries in the last 5 years, and more than 90% were deemed moderate-to-high or high-quality. Cost of therapy, time horizon, treatment cure rates, and recurrence rates were common influential factors in the study results.

The researchers found that fidaxomicin, a newer CDI drug, appears to be more cost-effective than other therapies, but not definitively. For initial CDI with no specific disease severity, fidaxomicin was found to be more cost-effective than metronidazole and vancomycin in two studies, but not in the study that accounted for severity. Two studies found fidaxomicin to be the most cost-effective treatment for initial severe CDI, but another concluded differently, possibly because of the higher cure rate of vancomycin and the higher cost of fidaxomicin. Three of five studies found that fidaxomicin was cost-effective for treating recurrent CDI.

The group also found that fecal microbiota transplantation (FMT) by colonoscopy was cost-effective for treating recurrent CDI in all four studies that analyzed it. But FMT via other routes was not found to be cost-effective.

The authors of the meta-analysis say that while fidaxomicin and FMT have opened up a new arena in CDI management, the high cost of these treatments (compared with vancomycin and metronidazole) means that further evaluation of their cost-effectiveness is needed. "Our review informs future research of areas that need improvement and may help policymakers and physicians to critically assess the cost-effectiveness of different CDI treatments," they write.
Feb 21 Infect Control Hosp Epidemiol abstract

 

WHO releases updated guidelines for management of latent TB

Originally published by CIDRAP News Feb 22

Updated guidelines on management of latent tuberculosis infection (LTBI) from the World Health Organization (WHO) call for expanded access to preventive treatment and testing along with new testing and treatment options.

LTBI is defined as a state of persistent immune response to stimulation by Mycobacterium tuberculosis antigens, with no evidence of clinically manifest active TB. People with a latent infection may develop active TB if they don't receive appropriate treatment.

The updated, consolidated guidelines include new recommendations on several different fronts, beginning with who should be prioritized for LTBI testing and preventive treatment. While previous guidelines have prioritized people with HIV and children under the age of 5 who have been in contact with people who have TB, the updated guidelines expand that group to include HIV-negative children, adults, and adolescents who are household contacts of people with bacteriologically confirmed TB. Select household contacts of patients with multidrug-resistant TB are also among those who may be considered for preventive treatment.

The updated guidelines also call for the use of either a tuberculin skin test or an interferon-gamma release assay in LTBI testing but note that such tests are not required for preventive treatment in people with HIV or child household contacts under the age of 5.

For treatment, the guidelines include shorter treatment options. Isoniazid monotherapy for 6 months remains the recommended treatment for children and adults, but rifampicin plus isoniazid daily for 3 months should be offered as an alternative in children and adolescents under the age of 15, and rifapentine plus isoniazid weekly for 3 months may be offered as an alternative for adults and children.
Feb 22 WHO updated guidelines for LTBI management

 

Platform uses metabolomic analysis to uncover novel antibiotics

Originally published by CIDRAP News Feb 21

A study today in Science Translational Medicine describes a new approach to determining the modes of action underlying antimicrobial compounds that could help speed the process of discovering novel antibiotics.

The platform developed by a team of European scientists involves rapid systematic metabolome profiling, a process that uses mass spectrometry to analyze and measure the changes that occur in metabolites—the small molecules produced by bacteria—upon treatment with a drug or compound. The idea is that these changes will provide clues to the underlying modes of action.

To test this strategy, the team exposed Mycobacterium smegmatis to multiple doses of 62 reference compounds with known modes of action, including currently used antibiotics and chemical stress agents, and used a computational framework to parse out predicted modes of action based on pairwise comparisons between known chemicals. They then tried this approach on 212 uncharacterized compounds from a drug discovery program by pharmaceutical company GlaxoSmithKline. This revealed 16 compounds that appeared to target unconventional cellular processes, and 6 with potentially new modes of action that exerted anti-tuberculosis effects by targeting fatty acid metabolism.

The authors of the study say the advantage of their approach for predicting modes of action in chemical screens is that it discriminates between compounds with previously known modes of action and those with new modes of action. "Knowing the MoAs [modes of action] of compounds at an early stage of drug discovery can guide the selection of the most promising leads, even in cases where the drugs do not yet exhibit strong bactericidal or bacteriostatic effects," they write.
Feb 21 Sci Transl Med study

 

CDC launches online antibiotic stewardship course

Originally published by CIDRAP News Feb 21

The US Centers for Disease Control and Prevention (CDC) yesterday launched a new online antibiotic stewardship course.

The interactive web-based activity is designed to help clinicians optimize antibiotic use to combat antibiotic resistance and improve healthcare quality and patient safety. The course will provide an overview of antibiotic resistance and explain the benefits of antibiotic stewardship across the healthcare spectrum. It will also discuss the risks and benefits of antibiotics, with a specific focus on the microbiome, adverse drug events, and C difficile infections. The first module will focus on outpatient antibiotic stewardship, and the following modules will focus on stewardship in acute care hospitals and long-term care facilities.

The CDC says the goal of the course is to help healthcare professionals deliver effective and consistent message about antibiotic use and antibiotic resistance to patients, and to provide guidance for how to apply antibiotic stewardship principles to the most common conditions that lead to inappropriate use. 
Feb 20 CDC training on antibiotic stewardship

 

Infection diagnostic codes tied to higher rates of previous antibiotics

Originally published by CIDRAP News Feb 21

Chicago researchers who analyzed data on 78,094 patients found that diagnostic codes for infections are strong surrogate markers for prior antibacterial exposure, especially to broad-spectrum antibiotics, which may help identify patients who harbor multidrug-resistant bacteria.

Writing in Infection Control & Hospital Epidemiology, the investigators, from Cook County Health and Hospital System in Chicago detailed findings from 121,916 hospitalizations involving 78,094 patients in three Chicago-area hospitals.

Of the 121,916 inpatient encounters, 24% had an associated infection code, 47% of patients received an antibacterial drug, and 13% received a broad-spectrum antibacterial. Patients with infection-related ICD-9-CM codes had more than twice the rate of antibacterial use compared with those lacking such codes (relative risk [RR], 2.29) and a fivefold increased risk for broad-spectrum antibacterial use (RR, 5.52). CD-9-CM codes were also linked to a tripling of the number of antibacterial days.

The authors concluded, "Such an association can be used to enhance early identification of patients at risk of multidrug-resistant organism (MDRO) carriage at the time of admission."
Feb 20 Infect Control Hosp Epidemiol abstract

 

CARB-X announces first award for 2018, two more funding rounds

Originally published by CIDRAP News Feb 20

CARB-X, a public-private collaboration that supports companies in early-state antibiotic discovery and development, recently announced its first funding award for 2018 and provided details about two funding rounds for the current year.

CARB-X said in a Feb 15 announcement that it is funding Curza, based in Salt Lake City, to support the development of a new class of antibiotics to treat a broad spectrum of life-threatening gram-negative bacteria that are resistant to currently available antibiotics. Curza's initial award is worth up to $2.2 million, with the possibility of $1.8 million more if it achieves certain milestones.

Kevin Outterson, JD, executive director of CARB-X, said in a statement from the group, "Curza's new class of antibiotics is an exciting addition to the Powered by CARB-X portfolio as it has been decades since the last new class was approved to for gram-negative bacteria." Curza's CZ-02 series is designed to kill bacteria with known resistance to other ribosomal antibiotics by binding to a clinically undrugged and highly conserved site on the bacterial ribosome.

The drugs have a unique mechanism that maximizes penetration of bacterial cells that leads to potent activity against drug-resistant ESKAPE pathogens, which include Enterococcus faeciumStaphylococcus aureusKlebsiella pneumoniaeAcinetobacter baumanniiP aeruginosa, and Enterobacter species.

In another CARB-X development, the group today announced two funding rounds, one open from Mar 22 through Mar 29, targeting new classes of direct-acting small-molecule and large-molecule antibacterials that target certain gram-negative bacteria. The second round is open from Jun 1 through Jun 8 and includes direct-acting therapies and a broader scope of vaccines, drugs, diagnostics, and devices that meet certain criteria.

Outterson said, "The scope of each funding cycle has been carefully designed to meet the most urgent needs in the global pipeline to treat drug-resistant bacterial infections and respond to the rising threat of drug resistant bacteria."
Feb 15 CARB-X press release
Feb 20 CARB-X press release

 

MRSA bacteremia rates higher in states with more African-Americans

Originally published by CIDRAP News Feb 20

A new analysis of hospital-onset methicillin-resistant Staphylococcus aureus bacteremia (HO-MRSAB) rates suggests that states with more African-American residents have higher incidence, researchers reported yesterday in Infection Control and Hospital Epidemiology.

In the study, researchers looked at state-level HO-MRSAB data for the year 2013 obtained from the Centers for Disease Control and Prevention and at census-derived demographic and socioeconomic variables. Although variations in HO-MRSAB rates among states have been explained by differences in the quality of infection-control practices, the researchers wanted to evaluate whether risk factors that have been well-studied at the individual level (including race, age, gender, and diabetic status) affect variations among populations.

Univariate analysis demonstrated significant positive correlations between HO-MRSAB rates and poverty rates, income inequality, percent of the population with diabetes, and the percent of the population that self-identify as African-American. But on multivariable analysis, the researchers found that African-American identity was the only variable that retained statistical significance.

While acknowledging that the findings suggest only a correlation and require further investigation, the authors of the study say that identifying population-level risk factors for HO-MRSAB is the first step toward developing risk-adjustment tools that would allow for more meaningful comparisons among states and more accurate estimates of the contribution of infection-control practices. 
Feb 19 Infect Control Hosp Epidemiol abstract

 

FAO warns about antimicrobial resistance in Asia-Pacific

Originally published by CIDRAP News Feb 20

Diseases originating in animals (called zoonotic diseases) and antimicrobial resistance (AMR) are converging in Asia-Pacific nations and threatening human health, the United Nations Food and Agriculture Organization (FAO) Regional Office for Asia and the Pacific warned today.

"We need to take action on AMR now because it affects us all," Juan Lubroth, DVM, FAO's chief veterinarian and AMR coordinator, said in an FAO news release. He added that antimicrobial overuse and misuse in humans and animals are resulting in the spread of AMR, which is complicating the treatment of many infectious diseases.

"Antibiotics and other antimicrobials are vital to treat sick animals and to protect public health by preventing the spread of disease and by keeping pathogens off our plates," Lubroth told delegates at the Prince Mahidol Awards Conference in Bangkok, where the theme of this year's annual conference is AMR and emerging infectious diseases.

"Governments have a responsibility to their country and to the global community to step-up and ensure that adequate regulations for antimicrobial use and distribution are in-place and enforced," said Lubroth, "This responsibility extends to providing incentive programmes and enabling mechanisms to help farmers transition away from an unsustainable dependency on antibiotics."

The FAO is working with Asia-Pacific countries such as Bangladesh, Cambodia, Laos, the Philippines, and Vietnam to develop and implement National Action Plans on AMR to raise awareness, promote good practices and legislation, and boost surveillance. The agency has also developed and piloted the Assessment Tool for Laboratories and Antimicrobial Surveillance Systems (ATLASS) in Cambodia, Indonesia, Laos, Thailand, and Vietnam to help them assess their national AMR surveillance systems and laboratories.
Feb 20 FAO regional office news release

 

Study finds anti-parasite drug effect against drug-resistant Staph

Originally published by CIDRAP News Feb 20

Investigators looking at the performance of three anti-parasite drugs against S aureus discovered that one of them, ivermectin, demonstrated potent anti-staphylococcal activity against some Staphylococcus isolates, including one that was resistant to methicillin and cefoxitin, according to a study today in Antimicrobial Resistance & Infection Control.

Canadian and Pakistani researchers tested ivermectin, levamisole, and albendazole against 21 S aureus isolates from bovine milk collected in Lahore and Faisalabad, Pakistan.

They found that ivermectin but not the other drugs exhibited a potent anti-staphylococcal activity at the concentrations of 6.25 and 12.5 micrograms per milliliter against two isolates. One of those isolates was sensitive to methicillin and cefoxitin, while the other was resistant to the two drugs.

The authors conclude, "Our novel findings indicate that ivermectin has an anti-bacterial effect against certain Saureus isolates. However, to comprehend why ivermectin did not inhibit the growth of all Staphylococci needs further investigation."
Feb 20 Antimicrob Resist Infect Control study

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