Stewardship / Resistance Scan for Dec 12, 2017

News brief

Clinicians call for more inclusive trials for new antibiotics

A letter today in the Journal of Infectious Diseases argues for relaxed criteria for patient exclusion in randomized controlled trials (RCTs) for new drugs to treat multidrug-resistant infections.

The letter, written by two Israeli clinicians, describes three patients with severe infections caused by carbapenem-resistant bacteria that presented during a single day at a hospital in Haifa. None of the three patients, the authors note, was eligible for an ongoing RCT at the hospital to assess the antibiotic cefiderocol—a novel siderophore cephalosporin in late-stage development—versus the best available therapy for bloodstream and other severe multidrug-resistant infections. All were treated with colistin as the only covering antibiotic.

These cases, the authors argue, point out a paradox. While it's estimated that more than 700,000 patients die each year from infections caused by multidrug-resistant pathogens, and plenty of patients with carbapenem-resistant infections are described in epidemiologic studies, finding patients for drug approval RCTs is difficult. That's because RCTs are often biased toward uncomplicated patients with a low risk of death, and the patients with the types of conditions described in their letter—neutropenia, severe sepsis, and organ failure—are often excluded from such studies. Yet these are the patients who may have the greatest need for new treatments.

While efforts to improve testing and approval requirements of new drugs for unmet needs have been commendable, the authors write, "We would like a discussion about the changes in regulatory guidance to the industry that would relax criteria for patient exclusion to ensure that the patients in [an] RTC resemble a bit more the patients in need of the antibiotic under study."
Dec 12 J Infect Dis letter

Commentary: Vaccines needed in the fight against AMR

Vaccines could and should play a key role in stemming the antimicrobial resistance (AMR) crisis, according to a commentary today in Nature.

The commentary, co-authored by the chief scientist at GlaxoSmithKline Vaccines and professors from Harvard T.H. Chan School of Public Health and Cincinnati Children's Hospital, calls for a global strategic effort to prioritize development of a portfolio of vaccines to target AMR.

Their reasoning is based on several factors. For one, they argue, vaccines almost never prompt bacteria to develop resistance. In addition, scientists have had much more success over the last 30 years developing new vaccines than they've had discovering new antibiotics. Since the 1980s, 22 new vaccines have been deployed in the clinic, while no new truly new class of antibiotics has been discovered or engineered. And vaccine technology continues to evolve.

Given this reality, and the fact that several current vaccines—such as the pneumococcal and influenza vaccines—have already helped directly and indirectly reduce the need for antibiotics, the authors say vaccines must be considered an essential element of the fight against AMR, along with new antibiotics, diagnostics, surveillance, and stewardship. Launching an effort to develop a portfolio of vaccines against AMR, they say, will require policymakers and stakeholders to raise awareness about the potential of vaccines to combat AMR, to persuade governments and drug companies of the cost-effectiveness of investing in vaccines, and to prioritize which bacterial strains should be targeted.

"Over the past few years, key institutional stakeholders — notably the [World Health Organization], the [United Nations General Assembly], the World Bank, the G20 group of countries, the European Union and the UK and US governments — have called for researchers to develop new antibiotics to expand our arsenal in the war against superbugs," the authors write. "We appeal to these organizations to call now for a multi-layered strategy that prioritizes the development of vaccines to target resistant strains."
Dec 12 Nature comment

News Scan for Dec 12, 2017

News brief

SIGA requests priority FDA review of its oral smallpox drug

SIGA Technologies of New York City announced yesterday that it has submitted its smallpox drug TPOXX (tecovirimat) for priority review by the US Food and Drug Administration (FDA).

If approved, the oral drug would be the first FDA-approved treatment for smallpox, a disease that has been eradicated but could be used as a bioterror weapon. The news comes on the heels of media reports that North Korea could be building a bioweapons program that might include smallpox.

TPOXX was developed to treat smallpox and other orthopoxvirus infections. SIGA has successfully delivered two million courses of TPOXX to the Strategic National Stockpile. No cure for smallpox currently exists, but lab personnel who work with smallpox or related viruses receive vaccination as a preventive measure.

SIGA CEO Phil Gomez, PhD, said in a news release, "Based on extensive positive efficacy data in animal studies and human clinical safety data without any drug-related serious adverse events, we believe the NDA [new drug application] for oral TPOXX is well positioned for favorable, expedited review by the FDA."

SIGA expects to receive notification from the FDA in February 2018 that its filing was accepted for review, as well as confirmation of priority review status and notification of a final action date.
Dec 11 SIGA news release
Dec 11 CIDRAP News scan on North Korea bioweapons

WHO: Flu on the rise in North America, parts of Asia

The World Health Organization (WHO) released a new global influenza update yesterday, showing that influenza is on the rise in North America, Western and Central Asia, and Europe.

In North America, the predominant strain has been influenza A, H3N2. Europe, however, has more influenza B circulating at this time. Both influenza A and B have been detected in Asia. In Western Africa, influenza A (H1N1) detections increased in Cote d'Ivoire and Ghana. Influenza B detections were reported in Central African Republic and Mozambique.

The temperate zones of South America continue to report low influenza-like illness (ILI) activity. The Caribbean and Central America also report low ILI activity.

Canada, the United States, and Mexico have all crossed the seasonal threshold for ILI. Adults over 65 have accounted for most influenza cases in the United States and just under half in Canada.

Worldwide, laboratories reporting to the WHO have typed 62.5% of viruses as influenza A and 37.5% as influenza B.
Dec 11 WHO update

Cholera outbreaks reported in Kenya, Zambia

Yesterday the WHO reported two outbreaks of cholera in Kenya and Zambia, with the Kenyan outbreak involving nearly 4,000 cases.

Between Jan 1 and Nov 29, Kenyan officials have reported 3,967 probable and confirmed cases of cholera, including 76 deaths. Transmission has been linked to camps, institutions, and mass gatherings. Community transmission is still ongoing in 7 Kenyan counties as of Nov 29, but 20 of 47 counties (43%) in the country have documented cholera cases this year.

The WHO said the risk of widespread transmission in Kenya is high. "Despite the decline in the number of cases reported, the outbreak appears to be clustered around two major types of settings. First, the refugee camps particularly Kakuma and Dadaab, and second in the populous Nairobi capital county," the WHO explained.

In Zambia, officials have reported 547 cases and 15 deaths since late September. Most cases are in the capital of Lusaka. The districts where cases have been documented have poor sanitation and water supply. A recent influx of refugees from the Democratic Republic of the Congo and the upcoming rainy season mean there's a strong chance the outbreak will grow in the coming months, the WHO said.
Dec 11 WHO Kenya report
Dec 11 WHO Zambia report