Stewardship / Resistance Scan for Aug 30, 2021

News brief

World Economic Forum warns of future risk, costs from waterborne AMR

A new report from the World Economic Forum predicts a future of rising risks and costs from waterborne antimicrobial resistance (AMR).

The report, published in collaboration with the Swiss Agency for Development and Cooperation, lays out the various drivers of AMR water pollution—hospital and community waste, food production, antibiotic manufacturing, and poor wastewater treatment—and the environmental and socio-economic factors that increase the risk associated with waterborne AMR.

With human and veterinary antimicrobial use expected to rise 28% and 50% by 2030, respectively, and antibiotic manufacturing to grow in response to this demand, the groups predict that waterborne AMR levels will climb, and the resulting human and economic costs will be highest in low- and middle-income countries where sanitation is poor and access to clean water is limited.

Among the impacts from higher levels of waterborne AMR will be increased disease burden, increased medical costs, additional costs to the wider economy due to reduced labor supply, and loss of livestock value from higher animal mortality rates.

"If these trends are left unchecked, the impacts will be severe and unaffordable in many countries," the report states. "Analysis for this study projects the effect of AMR pollution in water on the duration and quality of life up to 2050 to be equivalent to 25% of the total global burden of malaria and tropical diseases and more than the combined annual burden of conflict and terrorism, maternal disorders and natural disasters. Standard approaches to monetising these impacts value them at $340-680 billion per year."

The report estimates, for example, that an outbreak of drug-resistant cholera in Bangladesh, where only 35% of the population has access to hand washing at home and only 48% have access to sanitation, could double caseloads and significantly raise fatality rates.

The authors conclude that the scale and interconnectedness of waterborne AMR calls for a comprehensive, multisectoral response that includes expanded wastewater treatment and improved access to clean water, regulatory and incentive measures to promote prudent antibiotic use and responsible antibiotic manufacturing practices, and better data to improve understanding and monitoring of risk.
Aug 27 World Economic Forum report

Australian antibiotic use declining, but appropriateness still a problem

A new report from the Australian Commission on Safety and Quality in Health Care (the Commission) shows that community antimicrobial use has declined in Australia over the last few years, but inappropriate use remains an issue.

The fourth Australian report on antimicrobial use and resistance in human health (AURA 2021) shows that, in 2019, more than 10 million Australians (40.3%) had at least one antimicrobial dispensed. While age-standardized community antimicrobial prescribing rates in Australia have declined since 2015, the country continues to prescribe antimicrobials at a higher rate than most European countries and Canada. Furthermore, in 2019, more than 80% of patients diagnosed as having acute bronchitis or acute sinusitis—two conditions for which antimicrobials are not recommended—received an antimicrobial prescription.

"It is extremely concerning that AURA 2021 shows that many patients continue to be prescribed antimicrobials for conditions for which there is no evidence of benefit," John Turnidge, MBBS, the Commission's AURA senior medical adviser, said in a Commission press release.

The report also shows a continuing gradual increase in the volume of hospital antibiotic use since 2015, along with little improvement in the overall appropriateness of prescribing in various settings, including hospitals and nursing homes. Inappropriate antimicrobial use remained high for chronic obstructive pulmonary diseases, non-surgical wounds, and surgical prophylaxis.

Analysis of national antimicrobial resistance rates shows that resistance for many priority pathogens has not changed substantially since the last AURA report in 2019, with the exception of Escherichia coli, which is showing increasing resistance to common agents. In addition, community-associated clones of methicillin-resistant Staphylococcus aureus have become more widespread nationally.

The report calls for enhanced surveillance for important resistant organisms, strategies to address the lack of improvement in appropriate prescribing, and more accessible resistance data for healthcare providers.
Aug 27 AURA 2021 report
Aug 27 Commission press release

Antimicrobial stewardship intervention in sepsis patients found effective

Early intervention by an antimicrobial stewardship (AMS) team in patients being treated for sepsis improved the appropriateness of antimicrobial therapy, according to the results of a clinical trial published last week in JAC-Antimicrobial Resistance.

In the randomized controlled trial, conducted at a hospital in Melbourne, Australia, from February to August 2018, 90 patients who had a medical emergency team (MET) call for suspected sepsis were assigned 1:1 to either standard care (management of antimicrobial therapy by the treating team) or early intervention (AMS review of antimicrobial therapy within 48 hours of the MET call). The primary outcome was appropriateness of antimicrobial therapy 72 hours after the MET call, as determined by a panel of blinded infectious diseases physicians.

Previous research has indicated that approximately 50% of patients with suspected sepsis received prolonged antimicrobial therapy with unnecessarily broad-spectrum agents. While other trials have found that stewardship interventions can improve the appropriateness of antimicrobial therapy in critically ill sepsis patients, this is the first randomized controlled trial assessing the impact of a stewardship intervention in non-ICU sepsis patients, the authors said.

Seventy-two hours following a MET call for suspected sepsis, a higher proportion of patients in the intervention group were assessed as having appropriate antimicrobial therapy compared with the control group (67% vs 44%). The difference was even greater in a subgroup of patients who met sepsis-3 criteria (68% vs 36%).

The median time to appropriate antimicrobial therapy was shorter in the intervention group compared with the control group (43 vs 77 hours), and the median duration of total antimicrobial therapy was shorter (8.7 vs 10.7 days). There were non-significant differences in intensive care unit admission due to sepsis (13% in the intervention group vs 18% in the control group) and sepsis-related in-hospital mortality (7% vs 9%).

"In conclusion, our study demonstrates that in patients who have a MET call for suspected sepsis, AMS team review improves appropriateness of antimicrobial therapy by 23%," the study authors wrote. "By prioritizing this important cohort, AMS teams are able to provide a balanced approach to support early antimicrobial de-escalation and optimization for patients with suspected sepsis."
Aug 27 JAC-Antimicrob Resist study

News Scan for Aug 30, 2021

News brief

Antibody combo lowers hospitalizations in high-risk COVID-19 patients

High-risk adults with mild to moderate COVID-19 who receive a dose of casirivimab and imdevimab have lower hospitalization rates than those who don't, according to a randomized, controlled trial today in The Lancet's EClinicalMedicine. The casirivimab and imdevimab combination is under emergency use authorization by the US Food and Drug Administration.

Mayo Clinic researchers paired 696 intervention patients with 696 control patients from Arizona, Florida, Minnesota, and Wisconsin from Dec 4, 2020, to Apr 9, 2021. All were at high risk: 45.5% were 65 or older, and common underlying conditions included high blood pressure (52.4%), body mass index (BMI) of 35 kg/m² or higher (31.0%), diabetes (24.6%), chronic lung disease (22.1%), and chronic renal disease (11.4%). The antibody-treated cohort was mostly white (92.7%), female (51.4%), and had a median age of 63 years.

During follow-up at 14, 21, and 28 days post-treatment, the intervention group had significantly lower hospitalization rates across all time points (1.3% vs 3.3%, 1.3% vs 4.2%, and 1.6% vs 4.8%, respectively). While the absolute risk was only 3.2 percentage points at most, a Mayo Clinic press release points out this is a 60% to 70% relative reduction.

In both groups, intensive care unit (ICU) admission and mortality rates were similarly low, the researchers write. ICU admission peaked at 0.75% in the treatment group and 1.0% in the control group, and mortality was 0.15% in the treatment group versus 0.59% in the control group. Five patients died from any cause (one in the treatment group), and only seven patients in the treatment group had adverse events (fever, 4; shortness of breath, 2; nausea, 2; and chest pain, headache, or flushing, 1).

"Once again, this real-world study suggests that when patients who are at high risk due to a range of comorbidities contract a mild or moderate case of COVID-19, this combination of monoclonal injections gives them a chance of a nonhospitalized recovery," says senior author Raymund Razonable, MD.
Aug 30 EClinicalMedicine study
Aug 30 Mayo Clinic press release

COVID secondary attack rate has increased, meta-analysis suggests

In an updated review looking at the COVID-19 secondary attack rate (SAR) among household contacts, data showed an 18.9% SAR. The study, which was published late last week in JAMA Network Open, also suggested that the SAR grew from 13.4% to 31.1% from January 2020 to March 2021.

The researchers had previously looked at 54 studies published before Oct 19, 2020, which suggested a SAR of 16.6% (95% confidence interval [CI], 14.0% to 19.3%). With this study, they took 50 of those (four were excluded for overlapping populations) and added 37 studies from Oct 20, 2020, to Jun 17, 2021. The updated SAR came out to be 18.9% (95% CI, 16.2% to 22.0%).

The studies covered 1,249,163 household contacts from 30 countries, and the researchers found that adults had a higher SAR than kids (29.9% vs 17.5%), spouses had the highest SAR among household contacts (39.8% vs 18.3%), and those with comorbidities had a higher SAR than healthy contacts (50.0% vs 22.0%).

Symptomatic index patients appeared to generate higher SARs than asymptomatic or presymptomatic index patients (20.2% vs 3.0% and 8.1%, respectively), but the researchers note that many studies combined presymptomatic and symptomatic patients. In addition, most studies noted that asymptomatic index or secondary cases may have been missed.

Over the review period, the SAR appeared to increase from 13.4% (28 studies, January to February 2020) to 31.1% (15 studies, July 2020 to March 2021). B117, the most studied variant of concern in this research collection, also showed a higher SAR than with other COVID-19 lineages, with an aggregated SAR of 24.5%.

"More transmissible variants may be associated with further changes," the researchers write, although they note that time-trend biases may have affected their results. "Recent data suggest that 1 dose of a COVID-19 vaccine may be associated with reductions in the risk of household transmission by up to 50%, potentially supporting the case for universal vaccination and offering a path forward to protect household contacts."
Aug 27 JAMA Netw Open study

Children gained excess weight during pandemic, study finds

Children ages 5 to 17 years, especially those younger than 12, gained excess weight during the pandemic, according to a research letter late last week in JAMA.

The researchers looked at 191,509 healthy children in southern California's Kaiser Permanente health system and grouped them into three age-groups: 5 to 11, 12 to 15, and 16 to 17 years. The median age was 11.6 years, and the cohort consisted of 50.4% Hispanic children, 25.3% White children, 10.4% Asian or Pacific Islander children, and 7.0% Black children. Almost half (49.6%) were girls.

By comparing data from Mar 1, 2019, to Jan 31, 2021, the researchers found that the proportion of overweight or obese 5- to 11-year-olds increased from 36.2% to 45.7% (9.5 percentage points), while it varied only 5.2 percentage points and 3.1 percentage points in those 12 to 15 and 16 to 17, respectively. From the youngest to oldest age-groups, BMI increases were 1.57, 0.91, and 0.48.

"As children go back to school it will be important to focus on health and physical activity to help children not carry unwanted extra weight into adulthood," said senior author Corinna Koebnick, PhD, in a Kaiser Permanente press release.
Aug 27 JAMA study
Aug 27 Kaiser Permanente press release

Chronic wasting disease detected in Duval County, Texas

For the first time chronic wasting disease (CWD), a deadly prion disease affecting cervids like deer, elk, and moose, was detected in Duval County, Texas. The disease was found during routine surveillance of animal tissues at a deer-breeding facility.

Duval County is in the southern part of the state, between Loredo and Corpus Christi. The Texas A&M Veterinary Medical Diagnostic Laboratory in College Station detected CWD in a sample on Aug 18, which was confirmed on Aug 25 at the National Veterinary Services Laboratory in Ames, Iowa, according to the Texas Animal Health Commission (TAHC).

Officials said the detection will lead to immediate, additional investigations at the facility and surrounding areas.

"Early detection and containment remain critical strategies in our efforts to help mitigate the risk of further spread of this disease," said Carter Smith, MS, executive director of the Texas Parks and Wildlife Department, in a TAHC news release. "There is too much at stake across Texas to do otherwise."

According to the TAHC, CWD was first discovered in Texas in 2012 in free-ranging mule deer along a remote area of the Hueco Mountains in western Texas. It has since been detected in 260 captive or free-ranging cervids, including white-tailed deer, mule deer, red deer, and elk in 14 Texas counties.
Aug 27 TAHC press release

MERS-CoV infects 1 more person in Saudi Arabia

Saudi Arabia reported another MERS-CoV case, which involves a man from the city of Riyadh who had contact with camels, according to a statement from the Saudi Ministry of Health (MOH).

The man, age 69, isn't a health worker, and investigators don't think he was exposed to another sick patient. Saudi Arabia's most recent two cases, both reported in July, also involved people from Riyadh who had contact with camels.

In an Aug 17 update on MERS-CoV (Middle East respiratory syndrome coronavirus) in Saudi Arabia, the World Health Organization (WHO) said since 2012 it has received reports of 2,578 lab-confirmed MERS-CoV cases, along with 888 related deaths. Of those, 2,178 cases (84.5%) and 810 deaths were in Saudi Arabia.
Aug 26 Saudi MOH statement
Aug 17 WHO update