Stewardship / Resistance Scan for Feb 28, 2017

News brief

WHO calls for R&D into drug-resistant tuberculosis treatment

The World Health Organization (WHO) issued a statement today reaffirming the need for more research and development on new antibiotics for multidrug-resistant tuberculosis (MDR-TB).

"Addressing drug-resistant TB research is a top priority for WHO and for the world," WHO Director-General Margaret Chan, MD, MPH, said in a press release. "More than US $800 million per year is currently necessary to fund badly needed research into new antibiotics to treat TB."

The statement comes a day after the agency released a list of antibiotic-resistant "priority pathogens" for which new antibiotics are urgently needed. WHO officials said in a press conference yesterday that although drug-resistant TB is the most important priority for development of new antibiotics, it was not included on that list because it is already recognized as a top public health threat and is targeted by dedicated programs.

The WHO estimates there were 580,000 cases of MDR-TB globally in 2015 and 250,000 related deaths. Only two new antibiotics to treat MDR-TB have completed phase 2B trials in the past 50 years, the agency said, and both are still in phase 3 trials.
Feb 28 WHO press release

Study details drug-resistant bloodstream risks in organ transplants

A study yesterday in BMC Infectious Diseases details the factors most associated with mortality in abdominal organ transplant recipients with multidrug-resistant bloodstream infections.

In the retrospective study, investigators analyzed all episodes of multidrug-resistant gram-negative bacteremia (MDR-GNB) in abdominal solid organ transplant (ASOT) recipients at two Chinese hospitals from 2003 to 2016. Although the emergence of MDR-GNB in organ transplant recipients has been documented, information on risk factors for mortality has been scarce. To identify those risk factors, the investigators compared two groups of patients: those who survived and those who died within 30 days after the first episode of MDR-GNB.

During the 13-year study period, 2,169 patients underwent ASOT, and 99 MDR gram-negative samples (4.6%) were isolated from 91 patients with bloodstream infections. Of the 99 MDR-GNB isolates, 29 (29.3%) were Escherichia coli, 24 (24.2%) were Acinetobacter baumanni, 11 (11.1%) were Escherichia cloacae, and 10 (10.1%) were Klebsiella pneumoniae. The incidence of MDR-GNB was higher in liver recipients (12.3%) than in kidney recipients (2.6%). MDR-GNB-related 30-day mortality after the first episode of MDR-GNB was 39.6% (36 deaths).

Comparison of the two groups of patients showed that nosocomial origin, presence of other concomitant bloodstreams infections, increased creatinine level, and septic shock were the main risk factors for MDR-GNB–related mortality in ASOT recipients. Septic shock led to a 160-fold increase in mortality and was the strongest predictor of outcomes in multivariate models.

"Recognition of these factors is useful in identifying individuals who are at risk of mortality," the authors write.
Feb 27 BMC Infect Dis study

Researchers say antibiotic stewardship app boosted compliance

A study today in the Journal of Antimicrobial Chemotherapy reports that converting antimicrobial stewardship policies to a smartphone app modestly boosted compliance with prescribing policy at three hospitals in London, England.

The study looked at the 3 years before and after the 2011 rollout of the Imperial antibiotic prescribing policy application (IAPP), which was launched at the three main hospitals of Imperial College Healthcare Trust Hospitals in west London. The hospitals already had a multimodal antimicrobial stewardship program (ASP) in place; the purpose of IAPP was to make antimicrobial prescribing policy available at the point of care.

To measure the impact on antimicrobial prescribing pre- and post-IAPP adoption, the investigators chose three proxy indicators: adherence of choice of antimicrobial to local policy or microbiology/infectious disease team recommendation, documentation of stop or review dates on medication charts, and documentation of indication on medication charts. Data from general medical and surgical patients were analyzed separately.

The results of the interrupted time series analysis showed that compliance with policy increased in both medicine and surgery after IAPP was implemented, although the change in level of compliance was statistically significant only in surgery. IAPP also improved the documentation of the stop/review date in both medical and surgical specialties, but the improvement was not significant. Documentation of indication for prescribing, however, decreased significantly in both medicine and surgery after IAPP was implemented.

In conclusion, the authors note that the addition of IAPP to a multifaceted ASP did not demonstrate significant change in antimicrobial prescribing trends. The added value, they write, is in the "reach and access to the antimicrobial prescribing policy among a wider range of staff across our organization."
Feb 28 J Antimicrob Chemother study

News Scan for Feb 28, 2017

News brief

Federal ethics panel rejects proposal for human Zika challenge study

A federal ethics committee that reviewed a research proposal to experimentally infect humans with Zika virus to help gauge the best approach to a vaccine has rejected the application, according to a report posted last week and first reported today by Stat.

The expert panel, part of the National Institutes of Health (NIH), in December reviewed an application from the National Institute of Allergy and Infectious Diseases (NIAID) and Walter Reed Army Institute of Research.

In a 43-page report posted on the NIH Web site, the ethics panel said a human challenge study could be acceptable for studying the virus and vaccines against it in the future, but for now, studying the vaccine in regions where it is already spreading is a better option. The group also aired concerns about the potential risk to participants and others not involved in the study, such as sexual partners of the study subjects. Panelists also contended that there are other ways to develop vaccines that are reasonably protective.

Anna Durbin, MD, from Johns Hopkins University and a member of the team that proposed the human challenge study told Stat that a controlled human infection model could help streamline vaccine research, especially given that researchers face a closing window of opportunity to study the vaccine in a setting where researchers could more meaningfully gauge its protection. She added that among four main vaccine approaches, focusing on one that provides sterilizing immunity is a key goal.

Anthony Fauci, MD, NIAID director, told Stat that researchers can restructure their proposal to overcome the ethics obstacles.
Feb 28 Stat story
February NIH ethics panel report on Zika challenge studies

Sierra Leone study finds asymptomatic Ebola infections uncommon

Asymptomatic Ebola infections are uncommon even in highly exposed people and aren't likely to play a role in herd immunity, according to a seroprevalence study in Sierra Leone that used a new oral fluid immunoglobulin G test. A team led by researchers from Sierra Leone and Public Health England reported its findings yesterday in The Lancet Infectious Diseases.

After validating the test in survivors from Kerry Town Ebola treatment center and in controls from unaffected communities, the investigators tested household contacts of survivors. Results showed that the test was highly specific (100%) and highly sensitive (95.9%) in survivors.

Of 481 household contacts, 47.6% had high-level exposure such as contact with a corpse or contact with the body fluids of a sick patient. The researchers also found that 12% of them had some symptoms during the outbreak but were never diagnosed as having Ebola.

In Ebola-affected households, testing revealed asymptomatic infections in 2.3% of people and missed infections in 2.6%, suggesting that the levels of asymptomatic or missed illnesses are low.

The team concluded that asymptomatic infections don't seem to be a major contributor to herd immunity and that the noninvasive and easy-to-use test might be helpful for future investigations.

In a related commentary in the same issue, two researchers from the NIAID and the US Army Medical Research Institute of Infectious Diseases said the findings of the carefully conducted, well-controlled study cast doubt on earlier serosurveys from the 1980s and 1990s that implied high seroprevalence.

Though a single study doesn't settle the subclinical infection issue definitively, it does show that such illnesses aren't typical or widespread, the authors wrote. They added that the new swab-based test could be used to confirm or refute the earlier seroprevalence estimates.
Feb 27 Lancet Infect Dis abstract
Feb 27 Lancet Infect Dis commentary

Three new cases of MERS reported in Saudi Arabia

The Saudi Arabian Ministry of Health (MOH) announced three new cases of MERS-CoV yesterday, and two involved direct contact with camels.

The cases are from three different cities. A 74-year-old Saudi man from Bisha is in stable condition after presenting with symptoms of MERS-CoV (Middle East respiratory syndrome coronavirus) infection.

Two other patients are in critical condition, including a 76-year-old man from Hail who had direct contact with camels and a 29-year-old man from Riyadh whose disease is listed as primary, meaning it is unlikely he contracted the disease from another person.

The MOH observed another case on Feb 23. Information about that case, however, is in Arabic only on the MOH Web site, but the patient appears to be from Jeddah, according to a post from H5N1, an infectious disease news blog.

The cases raise the country's MERS total to 1,567 cases, including 651 deaths. Eleven patients are still being treated for the disease.
Feb 27 MOH update
Feb 23 MOH update
Feb 23 H5N1 blog post

Former BARDA deputy director Hatchett named CEO of CEPI

Yesterday the interim board of the Coalition for Epidemic Preparedness Innovations (CEPI) announced Richard Hatchett, MD, as its new chief executive officer, the organization said today in a press release. His position will begin in April.

Hatchett most recently worked for the Biomedical Advanced Research & Development Authority (BARDA) at the US Department of Health and Human Services (HHS), where he served as deputy director and chief medical officer. In previous roles at HHS and at the White House, Hatchett helped respond to significant public health crises, including recent Ebola, MERS and Zika outbreaks.

In the release, interim CEPI CEO Professor John-Arne Rottingen said, "Richard Hatchett has just the right combination of scientific insight and governmental experience to lead CEPI. Adding to this, he is a pragmatic leader with great diplomatic skills, which is suitable for leading CEPI by engaging both private and public sector partners as well as civil society."

CEPI is an international partnership that launched in January at the World Economic Forum. Its goal is to streamline and advance the vaccine pipeline for public health threats; its first targets will be MERS (Middle East respiratory syndrome), Lassa fever, and Nipah.
Feb 28 CEPI news release
Jan 18 CIDRAP News Story "New $460 million effort takes aim at MERS, Lassa, Nipah"

First high-level Chinese biosecurity lab accredited

Late last week, the government of China announced that its first accredited high-level biosafety laboratory will be put into service. This is the first lab of its kind in Asia, which will be used to study class four pathogens (P4), which pose a high-risk of aerosolized, person-to-person transmission, according to People's Daily, the communist party newspaper in China.

The lab will allow Chinese researchers to study viruses such as Ebola, and is located in Wuhan, the capital of Hubei province.

"Virus prevention and control knows no borders. China has been shouldering its responsibility in global public health care security in an active manner," said lab director Yuan Zhiming.

The lab was modeled after a P4 facility in Lyon, France. The lab has a sewage disposal system, filtered air and water systems, waste processing, and other top biosafety standards. The lab will also serve as a United National reference laboratory, storing virulent pathogens in a protected environment.

Canada, Germany, Australia, the United States, the United Kingdom, South Africa, and some other nations also have P4 laboratories.
Feb 28 People's Daily story