Our weekly wrap-up of antimicrobial stewardship & antimicrobial resistance scans

Report shows decline in Australian antibiotic use

A report this week from Australian health officials shows a consistent decline in the country's antibiotic use.

The report from the Australian Commission on Safety and Quality in Health Care looked at antibiotic prescriptions dispensed in all states and territories in the country from 2013-14 through 2017-18, with additional analysis of prescriptions for amoxicillin and amoxicillin-clavulanate. The results showed a downward trend in the number of prescriptions, the rate of prescriptions dispensed, and the volume of antibiotic use (number of defined daily doses dispensed per 1,000 people per day) compared with 2013-14.

Overall, 28.2 million prescriptions for antibiotics were dispensed in 2017-18, with a rate of 122,892 prescriptions per 100,000 people. That compares with 30.3 million prescriptions, and a rate of 126,864 prescriptions per 100,000 people, in 2013-14. Those trends were also observed for amoxicillin and amoxicillin-clavulanate, the second and third most prescribed antibiotics in Australia.

However, the report also notes that the volume of antibiotic use in 2017-18 (22.7 defined daily doses of antibiotics dispensed per 1,000 people per day) is more than twice the volume reported in the Netherlands (8.9) and Sweden (10.8), two countries with similar demographic profiles and standards of healthcare. In addition, socioeconomically disadvantaged areas of the country had higher antibiotic dispensing rates.

The authors of the report say that, to further optimize antibiotic prescribing in the country, efforts to educate the public and clinicians about appropriate antibiotic use need to continue.
Sep 23 Australian antibiotic dispensing report

Also this week, an organization representing Australian pharmaceutical and biotech companies announced the creation of the Australian Antimicrobial Resistance Network (AAMRNet).

The creation of AAMRNet was among the recommendations in a new "Fighting Superbugs" report from MTPConnect that came out of a meeting of stakeholders from the health, medical research, pharmaceutical, and government sectors held in November 2019 to develop an agenda for addressing AMR. Other recommendations from the report included the development of a national AMR research agenda, adoption of AMR-specific streamlined pathways for drug development, and creation of new regulatory incentives and reimbursement models to spur antibiotic development.
Sep 24 MTPConnect Fighting Superbugs report

CARB-X to fund development of drug for E coli urinary infections

Originally published by CIDRAP News Sep 22

CARB-X announced today that it will award drug maker GlaxoSmithKline (GSK) up to $7.51 million to develop a drug to treat and prevent urinary tract infections (UTIs) caused by Escherichia coli.

The award will help fund development of GSK3882347, an orally bioavailable small molecule drug that targets and binds itself to a protein (FimH) found on the surface of E coli, preventing the bacteria from binding to the bladder wall and causing an infection. GSK recently began a phase 1 study to explore the drug's safety, tolerability, and pharmacokinetics.

"GSK's project is in the early stages of development, and if successful, could potentially treat and prevent recurrent UTIs caused by E. coli and stop harmful bacteria from spreading in the body," CARB-X Research and Development Director Erin Duffy, PhD, said in a press release.

Since launching in 2016, CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) has awarded $250 million to accelerate the preclinical development of 68 antibacterial products. 
Sep 22 CARB-X press release

Study finds Japanese stewardship guidelines did not lessen antibiotic use

Originally published by CIDRAP New Sep 22

National guidelines to promote the appropriate use of antibiotics in Japan had no effect on trends in antibiotic use for patients with acute respiratory tract infection (ARTI) and gastroenteritis, Japanese researchers reported today in Infection Control and Hospital Epidemiology.

Using data from a national claims database from June 2016 to June 2018, researchers from the University of Tokyo examined antibiotic use for ARTI or gastroenteritis among outpatients 6 years and older. To determine whether guidelines issued by the Japanese government in 2017 on clinical management of ARTI and gastroenteritis had any impact on antibiotic prescribing for those conditions, they conducted an interrupted time series analysis to calculate the season-adjusted changes in the rate of antibiotic prescriptions in the year before and the year after the guidelines were issued.

Previous studies had found that more than 70% of oral antibiotics prescribed in Japan in 2012 and 2013 were for those two conditions, often unnecessarily.

A total of 13,177,735 patients with ARTI and 300,565 patients with gastroenteritis were evaluated in the 2-year study period. Among patients with ARTI, there was a significant downward trend in antibiotic use during the 2-year study period (−0.06% per week; 95% confidence interval [CI], −0.07% to −0.04%), but there was no significant change in trends of antibiotic use between the pre-issue period and post-issue period (trend difference, −0.01% per week; 95% CI, −0.10% to 0.07%).

Similarly, for patients with gastroenteritis, there was no significant change in the trends of antibiotic use between the pre-issue period and post-issue period (trend difference, −0.02% per week; 95% CI, −0.04% to 0.01%). Similar associations were observed in analyses for broad-spectrum antibiotic use.

"Our findings indicate that the issue of national guidelines may not be an immediately effective intervention to change the prescribing behaviors of general practitioners, and they suggest the importance of further multifaceted strategies to promote optimal antimicrobial use," the authors of the study wrote. They suggest that financial incentives, prescribing restrictions, and clinician and patient education are strategies that should be explored.
Sep 22 Infect Control Hosp Epidemiol abstract

Experts suggest steps for creating better market for new antibiotics

Originally published by CIDRAP News Sep 21

A new report from a panel of experts in antimicrobial resistance and antibiotic development suggests that a series of incremental steps will be needed to create a sustainable market for antibiotics.

The report from the Duke-Margolis Center for Health Policy lays out the short-term, medium-term, and long-term post-market incentives needed to revive investment in innovative antibiotics, along with the limitations of those approaches. The incentives are intended to solve what has become the most significant challenge to antibiotic development: the lack of sufficient financial return on new antibiotics.

"Reinvigorating the market for antibiotics requires action immediately, but the most impactful changes may not be feasibly implemented in the short-term," the authors write. "As a result, the spectrum of needed incentives must be considered in the context of time and complexity to implementation; some incentives might be limited in impact, but can be put into action quickly and provide immediate relief."

Among the short-term incentives highlighted is the rule changes made in 2019 by the Centers for Medicare and Medicaid Services to increase hospital reimbursement for new antibiotics. An intermediate step is the Developing an Innovative Strategy for Antimicrobial Resistant Organisms (DISARM) Act, which was re-introduced in Congress this year but was ultimately removed from coronavirus relief legislation. Under DISARM, hospitals would be reimbursed for qualified antibiotics based on their average sales price, a move the authors say would mitigate the financial impact on hospital pharmacies that procure and dispense innovative antibiotics.

Long-term strategies include market entry rewards, which would involve large upfront payments of up to $1 billion to companies that develop innovative new antibiotics, and subscription payment models, in which antibiotic developers would receive recurring payments for antibiotics in exchange for the reliable availability of those antibiotics. The idea behind this type of model, variations of which are being tested in the United Kingdom and Sweden, is to create a reimbursement system for antibiotics based not on sales volume but on the drugs' medical value.

The authors say that implementing these steps, and overcoming their limitations, will require multiple stakeholders to design methods to determine the value of antibiotics; collaborate to improve data collection on antibiotic use, AMR, and patient outcomes; and align around common investment goals and post-market incentives.
Sep 18 Duke-Margolis Center for Health Policy report

Demographics, underlying conditions tied to worse COVID in health workers

Today's Morbidity and Mortality Weekly Report (MMWR) provides updated information from voluntary reports on 100,570 healthcare personnel (HCP) with COVID-19 from February to July that shows variations in risk, including higher death rates in minority workers.

The authors analyzed data from standardized case report forms containing HCP demographic characteristics, including newly reported occupation type and job setting, underlying medical conditions, hospitalizations, and intensive care unit (ICU) admissions and deaths.

The number of HCP with COVID-19 increased tenfold since first described in April, with 641 deaths. Demographic factors and preexisting conditions were predictive of poorer outcomes. Infected HCP who were older, male, Asian, or black—or had one or more underlying medical conditions—had higher death rates. 

"Long-standing inequities in social determinants of health can result in some groups being at increased risk for illness and death from COVID-19, and these factors must also be recognized and addressed when protecting essential workers in the workplace, at home, and in the community," the report states. 

The most commonly reported job settings for HCP COVID-19 cases were nursing homes and residential care facilities—67% of cases with reported job settings—with nurses representing the most common occupation—30% of cases with known occupation type.

The report does not identify the source of HCP exposure or infection but highlights the critical need for continued surveillance of HCP environments, personal protective equipment access and training, universal use of masks in work and community settings, and observing physical distancing guidelines to minimize the risk to HCPs and patients.
Sep 25 MMWR report

COVID-19 during pregnancy not associated with complications in infants

A Swedish study of pregnant COVID-19 patients giving birth at Karolinska University Hospital in Stockholm from Mar 25 to Jul 24 found a higher likelihood of labor complications, but no significant differences in outcomes in newborns compared with COVID-19–negative women.

Published in JAMA this week, the study tested women in labor using reverse-transcriptase polymerase chain reaction (RT-PCR) on nasopharyngeal swabs to identify COVID-19–positive patients. Among 2,682 women, 156 (5.8%) were SARS-CoV-2 positive and 65% of those who tested positive were asymptomatic—meaning they had no symptoms compatible with COVID-19.

COVID-19–positive laboring women were more likely to experience preeclampsia—a serious labor complication characterized by high blood pressure and protein in the urine—and less likely to undergo labor induction for reasons that are yet unclear. Lead author Mia Ahlberg, RNM, PhD, of Karolinska said in a university news release, "One possible reason for the latter is that both preeclampsia and COVID-19 impact several organs and can present similar symptoms."

No significant differences were noted for other maternal outcomes (mode of delivery, postpartum hemorrhage, and preterm birth) between COVID-19–positive and –negative groups. Neonatal outcomes, including 5-minute Apgar scores, birth weight for gestational age, prevalence of birth defects, and stillborn births, did not differ significantly between the groups.

The study authors write, "In light of other accumulating data, it is already clear that COVID-19 is less severe in pregnancy than the 2 previous coronavirus infections: severe acute respiratory syndrome–related coronavirus (SARS) and Middle East respiratory syndrome–related coronavirus (MERS). Nevertheless, there are reports of pregnant persons requiring critical care, and there have been other reports of both mother and infant deaths in association with COVID-19."

While encouraging, the study was limited by the number of laboring women presenting with COVID-19 symptoms, which restricts the ability to generalize to larger populations and different locations.

Ahlberg says, "Larger studies should be conducted to be able to identify if women with symptoms and different degrees of symptoms constitute a risk group for adverse outcomes such as preterm birth."
Sep 23 JAMA study
Sep 23 Karolinska Institutet news release

Children, adolescents less susceptible to COVID-19, meta-analysis finds

A systemic review and meta-analysis in JAMA Pediatrics today found that children and adolescents have a significantly lower susceptibility to COVID-19 than adults do. Previous studies have reached similar conclusions, but this study pools data from 32 studies to get a clearer overall picture.

Children and adolescents younger than 20 years were nearly half as likely to be infected than adults (odds ratio, 0.56; 95% confidence interval, 0.37 to 0.85) in the review of studies that involved contact tracing or population screening through Jul 28 and included a total of 41,640 children and adolescents and 268,945 adults. The decreased risk of infection was most pronounced in children younger than 10 to 14 years, "with adolescents appearing to have similar susceptibility to adults," the study authors write.

Infection and transmission rates in children have important implications for public health decisions regarding lockdowns and school closures. While available studies show evidence of transmission of SARS-CoV-2, the virus that causes, COVID-19, from children to other age-groups, the review contained relatively few data on transmission and was unable to elucidate a clear role.

The authors conclude, "Preliminary evidence suggests that children have a lower susceptibility to SARS-CoV-2 infection compared with adults, but the role that children and adolescents play in transmission of this virus remains unclear."

In a commentary in the same publication, Saul Faust, MD, writes, "In spite of everything we have known and understood about respiratory viral infections to date, it does now appear that children overall are relatively less susceptible to becoming infected as well [as] having less severe infection itself. How infectious children are once they have acquired the SARS-CoV-2 virus remains unclear. Studies have confirmed children carry viable virus in their nasopharynx, so children are almost certainly infectious."

Faust advocates for prioritizing the needs of children and young people in policy decisions around reopening of society, including ongoing studies of the role of transmission in schools, and making data-driven decisions that avoid politicization and take local community data, resources, and specific community needs into account.
Sep 25 JAMA Pediatrics study and commentary