Stewardship / Resistance Scan for May 27, 2020

News brief

Review supports WHO guidance against post-surgery antibiotics

A review and meta-analysis of randomized controlled trials (RCTs) has found no conclusive evidence that post-operative antibiotic prophylaxis reduces incidence of surgical-site infections, a finding that supports the World Health Organization's (WHO's) recommendation for discontinuation of the practice, researchers reported yesterday in The Lancet Infectious Diseases.

The aim of the review, which was conducted by Dutch, Swiss, and US researchers, was to update and reassess the evidence upon which the WHO's 2016 recommendation was based. The WHO's Global Guidelines for the Prevention of Surgical Site Infections, put together by a panel of 20 experts in infection control, recommended that prophylactic antibiotics be administered 2 hours before incision or during the surgery to prevent infections, but not after, based on a lack of evidence that post-surgery antibiotics reduce infections. Despite this advice, the practice remains common worldwide, with antibiotics frequently continued for days after surgery.

The reviewers identified 83 relevant RCTs, with 52 (involving 19,273 participants) comparing post-operative continuation of antibiotics for 1 to 5 days with immediate discontinuation. The initial meta-analysis of those 52 RCTs showed an indication of a benefit of post-operative continuation of antibiotics in preventing surgical-site infection (relative risk [RR], 0.89; 95% confidence interval [CI], 0.79 to 1.00).

But further analysis showed that compliance with best practice standards for surgical antibiotic prophylaxis, such as timely administration of the first dose, modified the results. In the 27 trials that were not compliant with best-practice standards, continuation of antibiotic prophylaxis after surgery was associated with a reduction in surgical-site infections compared with immediate discontinuation (RR, 0.79; 95% CI, 0.67 to 0.94). But in the 24 studies that did meet best practice standards, no benefit was found (RR, 1.04; 95% CI, 0.85 to 1.27).

The meta-analysis also found that, when costs and adverse events were reported, post-operative continuation of antibiotics appeared to increase costs and lead to more adverse events.

"Our findings support WHO recommendations against the practice of continuing surgical antibiotic prophylaxis postoperatively," the authors concluded. "Considering the associated adverse effects—in particular, antimicrobial resistance—this prevalent practice has no basis."
May 26 Lancet Infect Dis abstract

British report highlights high antibiotic use in US livestock, trade concerns

A new report shows antibiotic use in food-producing animals is much higher in the United States than the United Kingdom, and warns that a potential US trade deal with Britain risks reversing the progress that British farmers have made in reducing antibiotic use in livestock.

Using data from the US Food and Drug Administration, the United Kingdom's Veterinary Medicines Directorate, and the European Medicines Authority, the UK-based Alliance to Save Our Antibiotics compared US and UK antibiotic use by farm-animal species and found that total antibiotic use in US farm animals is more than five times higher than in UK farm animals, with US cattle receiving eight to nine times as many antibiotics as UK cattle. The comparison takes into account the size of the different livestock populations.

The comparison was made to highlight how the United Kingdom's pending exit from the European Union could threaten food safety and animal welfare standards. With the government planning to cut tariffs on importation of meat from countries with which it does not currently have a free trade deal, that could mean a significant increase in meat and dairy imports from the United States, which has less restrictive policies on the use of antibiotics and growth promoters in animals than the UK or the EU. Most imported meat in Britain currently comes from the EU.

"US farmers continue to massively overuse antibiotics despite increasing warnings about the threat this poses to human health," Alliance scientific advisor Cóilín Nunan said in a press release. "British consumers should be concerned if a UK-US trade deal results in increasing imports of US meat and dairy produced in this way, as we know that antibiotic-resistant bacteria can pass to humans through the food chain."

According to the report, US livestock industry representatives and lobbyists have insisted that in any trade deal, UK farmers should adopt US standards. Among the many concerns expressed is that the US government is opposed to banning the use of antibiotics to prevent disease in livestock, as has been recommended by the WHO. An EU ban on preventive antibiotic treatment will go into effect in 2022

The report notes that British farmers cut their antibiotic use by 50% from 2014 through 2018, while antibiotic use on US farms increased by 9% in 2018 after several years of decline.
May 27 Alliance to Save Our Antibiotics report
May 27 Alliance to Save Our Antibiotics press release

Study: Conventional, organic dairy farmers differ on antibiotic use, resistance

A study exploring perceptions about antibiotic use and resistance in dairy farming suggests conventional and organic farmers have differing views that align with their respective business practices, researchers from Cornell University report today in PLOS One.

For the study, the researchers conducted semi-structured interviews with farmers representing 20 dairy farms in New York state—15 conventional and 5 US Department of Agriculture–certified organic farmers—and used thematic analysis to compare and contrast the farmers' characterization of their beliefs, values, and concerns. Among the themes they found was that, for conventional farmers, concerns about antibiotic use and resistance mainly related to the near-term impact on their livestock should antibiotics lose their efficacy, rather than the potential impact on human health. Conventional farmers also believed their antibiotic use was judicious, even if it didn't always fit the definition of judicious use, and felt that further regulation on antibiotic use could threaten their cattle's health.

In contrast, organic dairy farmers expressed more concern about antibiotic resistance, frequently framed it as a public health issue, and exhibited a more detailed understanding of judicious antibiotic use. Both groups had similar doubts about shared concerns about the impact of marketing and consumer perceptions on dairy, and emphasized herd health management as an effective preventive tool that could limit the need to antibiotics.

The authors of the study say the findings provide some targets for additional research and educational interventions.

"Given farmers' interest in disease prevention, they would likely be amenable to interventions focused on improving the efficiency and financial viability of their operation through improved herd health practices, including optimal antibiotic use/best practices," they write. "Such interventions would likely be best delivered by a veterinarian given farmers' trust of them."
May 27 PLOS One study

News Scan for May 27, 2020

News brief

Study shows loss of smell and taste among COVID-19 patients

A study yesterday in the Annals of Internal Medicine of more than 2,000 Europeans diagnosed as having mild to moderate COVID-19 shows that 87% reported loss of smell, and 56% reported taste dysfunction. The study suggests olfactory symptoms and taste disorders may be a common feature of COVID-19 infection.

The study was based on surveys completed by 2,013 patients diagnosed as having COVID-19 in one of 18 European hospitals from Mar 22 through Apr 23. Only 8% of participants required hospitalization for their infections, and none required intensive care.

Most patients reported a loss of smell after experiencing other general and otolaryngologic symptoms, the authors said. The patients reported smelling-related symptoms for a mean of 8.4 days, with 60.9% of patients regaining their sense of smell 5 to 14 days after the onset of smell loss.

"These findings highlight the importance of considering loss of smell and taste in the diagnosis of mild to moderate COVID-19," the authors concluded.
May 26 Ann Intern Med study

Household, frequent contacts at highest risk of secondary COVID-19, study finds

The secondary COVID-19 attack rate in presymptomatic people in Guangdong province, China, was 16.1% among household contacts, 1.1% among social contacts, and 0 for workplace contacts, according to a study published yesterday in Emerging Infectious Diseases.

The researchers analyzed contact-tracing surveillance data gathered from Jan 28 to Mar 15 on 38 asymptomatic people and 369 of their close contacts. The secondary attack rate (SAR) is the percent of those who become infected by a primary, or index, case-patient.

The investigators determined an overall SAR of 3.3% (95% confidence interval [CI], 1.9% to 5.6%). Contacts 60 years and older had the highest SAR, at 8.0%, versus 1.4% to 5.6% in younger contacts. The SAR for asymptomatic index patients was 0.8%, rising to 3.5% in mildly symptomatic people, 5.7% in those with moderate symptoms, and 4.5% in those with severe disease.

Household contacts were at 12 times the risk of infection, while those with more than five contacts with the index patient in the 2 days before they tested positive were at 29 times the risk of infection.

The baseline reproduction number (R nought [R₀)]) was 0.3 (95% CI, 0.2 to 0.5), much smaller than the previously reported overall R₀ of 2.2, which could be attributed to active surveillance, centralized quarantine, and stringent social-distancing, the authors said. The R₀ indicates how many people a single person will infect.

The study "underlines the need for prompt contact-based surveillance and social distancing," the authors wrote. The researchers also noted that asymptomatic people were less likely to transmit the virus than those with symptoms. "However, this finding should not discourage isolation and surveillance efforts," they said.
May 26 Emerg Infect Dis study

Poll sees increased US demand for flu vaccine

About 60% of US adults plan to be vaccinated against flu in the upcoming season, according to a new Reuters/Ipsos poll, which is above the 45.3% uptake in adults that the US Centers for Disease Control and Prevention (CDC) reported for last season.

The flu vaccine isn't expected to provide any protection against COVID-19, but experts say vaccination could prevent coinfections and lessen the burden on the healthcare system, especially during fall and winter respiratory illness season.

Researchers conducted the poll of 4,428 adults from May 13 to 19, and it has a margin of error of minus or plus 2%. Those most likely to say they would be vaccinated included Democrats, white respondents, those with higher household incomes and college degrees, and those who live in suburban or urban areas.

In a related development, US pharmacies are scaling up their plans to address a surge in demand for flu vaccine, according to a separate Reuters report. The Rite Aid chain said it has increased its order for flu shots by 40% for the upcoming season, and other chains such as CVS, Walmart, and Walgreens are also expecting more demand. Australia-based flu vaccine maker CSL Ltd said demand from its customers is up 10%, and GlaxoSmithKline said it is ready to expand production as needed.
May 26 Reuters story
CDC flu vaccine coverage for the 2018-2019 season
May 26 Reuters story on pharmacy plans

Amivas: US FDA approves injectable artesunate for severe malaria

Drug maker Amivas today announced US Food and Drug Administration (FDA) approval of injectable artesunate for the initial treatment of severe malaria in adults and children.

Injectable artesunate, an artemisinin derivative, is on the World Health Organization Model List of Essential Medicines.

Artesunate has been available in the United States since 2007 only through an expanded-access investigational new drug program managed by the Centers for Disease Control and Prevention (CDC). It was developed by the Walter Reed Army Institute of Research and the US Army Medical Materiel Development Activity.

Two clinical trials on artesunate treatment of 6,886 adults, children, and pregnant women showed that the drug reduced the death rate by 34.7% and 22.5% versus the injectable standard-of-care drug, according to Amivas' press release. Another study, involving 92 malaria patients treated with artesunate from January 2007 to December 2010, found a death rate of 6.9%.

Amivas said that the CDC will continue to offer artesunate until Amivas, headquartered in Frederick, Maryland, makes it available nationwide in the coming months.

About 2,000 people in the United States are diagnosed as having malaria each year. Untreated, the mosquito-borne disease causes severe disease in about 15% of infected people, in whom the death rate is nearly 100%.
May 27 Amivas press release