Stewardship / Resistance Scan for May 18, 2017

News brief

CDC reports count of US Candida auris infections up to 77 cases

In today's Morbidity and Mortality Weekly Report, investigators from the Centers for Disease Control and Prevention (CDC) and several state health departments say a total of 77 clinical cases of the emerging multidrug-resistant fungus Candida auris have now been reported from seven states. New York has the most reported cases with 53, followed by New Jersey (16), Illinois (4), Indiana (1), Maryland (1), Massachusetts (1), and Oklahoma (1).

C auris was originally discovered in 2009 in Japan and since then has emerged as a global health threat due to its growing resistance to all three major classes of antifungals used to treat Candida infections. The CDC estimates the mortality rate of C auris infections at approximately 60%.

Among the 77 clinical cases, median patient age was 70 years and 55% were male, and nearly all patients had underlying health conditions and extensive exposure to healthcare facilities. The report says epidemiological connections have been found between most cases, with further investigation revealing that many of the New York and New Jersey patients had overlapping stays at interconnected long-term care facilities and acute care hospitals within a limited geographic area. The case in Massachusetts was linked to the Illinois cases, and the cases in Oklahoma and Maryland involved patients who had received healthcare outside the country.

Antifungal susceptibility tests of the first 35 clinical isolates found that 30 (86%) were resistant to fluconazole, 15 (43%) were resistant to amphotericin B, and 1 (3%) was resistant to echinocandins. Whole-genome sequencing showed that isolates from within each state were highly related to one another and linked to isolates found in South Asia and South America, suggesting they had been introduced from outside the country and then transmitted locally.

Screening of 390 close contacts, primarily individuals who were on the same hospital ward as the infected patients, identified an additional 45 patients who were colonized with C auris (24 in New Jersey, 17 in New York, and 4 in Illinois). Environmental testing detected C auris on a variety of hospital surfaces.

To help curb the spread of the fungus, the CDC recommends using standard and contact precautions for infected and colonized patients, housing patients in private rooms, cleaning patient rooms daily with a disinfectant active against Clostridium difficile, and informing receiving healthcare facilities when an infected or colonized patient is being transferred.
May 18 MMWR Notes from the Field

Antibiotic use rises in South Korea

A review of a large health insurance claims database has found that antibiotic usage in South Korea rose by more than 17% from 2007 to 2014, researchers reported yesterday in PLoS One.

To investigate antibiotic usage in South Korea, a country known for high utilization of antibiotics and high rates of antibiotic resistance, researchers used data from the Health Insurance Review & Assessment Service, which represents nearly the entire South Korean population. Annual usage was calculated as defined daily doses per 1,000 inhabitants per day (DID). Antibiotic usage was analyzed for the entire population and for various subgroups.

Overall, the researchers found that total antibiotic usage in South Korea rose from 23.5 DID in 2007 to 27.7 DID in 2014, with inpatient use seeing a slight decrease but use among outpatients, male and female patients, and all age groups seeing an increase. Antibiotic use was highest among patients younger than age 6 in all years and rose from 47 DID in 2007 to 59.21 in 2014. DIDs of penicillins, cephalosporins, macrolides, and fluoroquinolones all increased over time.

The authors of the study say the findings could be a useful guide for designing public health intervention strategies to promote appropriate antibiotic use.
May 17 PLoS One study

News Scan for May 18, 2017

News brief

Report describes rapid Zika spread, impact of control steps in Singapore

In the first-of-its-kind comprehensive review of a Zika outbreak in Asia, researchers from Singapore yesterday reported how easily the virus can be introduced and spread even when vector control programs are good, adding that response measures had a measurable impact on curbing the disease. Writing in The Lancet Infectious Diseases yesterday, the team described an outbreak that began in August 2016.

From August through November 2016, Singapore confirmed 455 Zika cases, with the outbreak occurring in an area at high risk for dengue transmission and near a construction site where control of mosquito breeding was difficult. During the first phase of the outbreak, health authorities isolated sick patients in the hospital in an attempt to prevent the virus from spreading, but it had already moved into the local mosquito population. Officials then focused on community engagement and vector control.

The team estimated that after authorities implemented response steps, over a 4-week period the reproductive number (R0) declined from 3.62 to 1.22.

Phylogenetic analysis of human and mosquito Zika strains showed little diversity and found the virus was distinct from other Asian strains, with the most common ancestor from May 2016. Analysis suggests at least three separate importations, but only one lineage caused the large outbreak.

The investigators concluded that prompt national action involving many sectors can help curb the spread of the virus and that lessons learned in Singapore's outbreak might be useful for other countries.

A related commentary by two experts from French Polynesia and the United States said the Singapore findings raise several questions, such as why the virus sparked an outbreak in 2016 when it had been in Asia for decades and why Zika appeared to be more contained than dengue virus.
May 17 Lancet Infect Dis abstract
May 17 Lancet Infect Dis commentary

Analysis of H7N2 from NY vet shows mild infection, low spread in ferrets

Experiments with the H7N2 virus linked to a recent outbreak in shelter cats, which resulted on one infection in a veterinarian, revealed mild illness and poor transmission in small mammals, scientists from the US Centers for Disease Control and Prevention (CDC) reported yesterday in the Journal of Virology.

The detection in the veterinarian marked the first known human H7N2 illness since 2003. In December 2016 the low-pathogenic avian influenza strain was implicated in an outbreak at a cat shelter in New York City, spreading to similar facilities in that state and Pennsylvania. Given the close connection between humans and pet cats, CDC researchers conducted several experiments in mice and ferrets to better understand the threat to mammals, including people.

They found that H7N2 caused mild or transient illness in the mice and ferrets, which did not transmit it following two different inoculation methods. Environmental persistence was similar to other H7N2 viruses.

However, the H7N2 strain isolated from the veterinarian replicated more easily in human bronchial cells compared with other H7N2 viruses. The team found that the hemagglutinin of the novel strain was activated at a lower pH, similar to human influenza viruses.

They concluded that H7N2 would need to adapt further before it became a greater public health threat and that their findings underscore the need to continuously monitor emerging zoonotic threats.
May 17 J Virol abstract
Dec 27, 2016, CIDRAP News scan "Vet contracts H7N2 virus from cats in New York City"

Research funding groups endorse new clinical trial reporting standards

Nine of the world's largest research funders today agreed on new standards that require all clinical trials they fund or support to be registered, with the results disclosed publicly, an effort to provide a clearer picture of the risks and benefits of vaccines, drugs, and medical devices.

The groups, which include the Wellcome Trust, PATH, and the Bill and Melinda Gates Foundation, agreed to develop and implement policies within the next 12 months, according to a statement from the World Health Organization (WHO). The plan incorporates recommendations from a 2015 WHO position paper on public disclosure of results from clinical trials and builds on the World Medical Association's 2012 Helsinki Declaration.

About 50% of clinical trials go unreported, often because of negative results, which can lead to an incomplete and possibly misleading impression of risks and benefits and to suboptimal or even harmful products, according to the WHO.

Marie-Paule Kieny, PhD, the WHO's assistant director-general for health systems and innovation, said in the statement, "Research funders are making a strong statement that there will be no more excuses on why some clinical trials remain unreported long after they have completed."

Jeremy Farrar, MD, PhD, Wellcome Trust director, said that the more transparent system spelled out in the agreement will also reduce reporting biases, which favor publication of trials that produce positive results.

By signing the agreement, the groups also agreed to monitor compliance with registration requirements and endorse the development of systems to monitor results reporting. Other signatories include the Indian Council of Medical Research, the Norwegian Research Council, the UK Medical Research Council, the Doctors without Borders research arm, and the Pasteur Institute.
May 18 WHO press release