Stewardship / Resistance Scan for Apr 01, 2021

News brief

ReAct report lays out challenges, solutions for antibiotic access

A new report from antibiotic research and development (R&D) advocacy group ReAct outlines the challenges and solutions for creating a new model that will deliver sustainable access to antibiotics for all countries.

Arguing that governments around the world have so far failed to respond with either the scale or the urgency required to address rising antibiotic resistance, the decreasing effectiveness of current antibiotics, and the weak pipeline of new antibiotics, the report lays out five key challenges that governments must solve to achieve sustainable access to affordable, effective antibiotics. The model outlined considers how the entire chain of stakeholders in antibiotic development, from pharmaceutical companies to investors to governments, should work together.

The five challenges identified are setting research priorities that address the most significant and unmet global health needs; overcoming the scientific barriers in the early discovery and research phases for new antibiotics; financing late-stage clinical R&D without relying on price and sales revenues of the end-products; ensuring sustainable, environmentally appropriate production, quality, procurement, and registration of novel antibiotics; and ensuring sustainable, equitable access to new antibiotics in all countries in a manner that guarantees safe and responsible use.

Among the recommendations to address these challenges are establishment of a global entity for early-stage R&D, increasing public funding of early-stage research, fully delinking the cost of antibiotic R&D from the expectation of sales revenues, and adopting national legislation that sets antibiotic production standards.

"Today it is almost thirty-four years since the last class of antibiotics was discovered. The world cannot afford another 30 years of stalemate," ReAct founder Otto Cars, MD, PhD, a professor of infectious diseases at Sweden's Uppsala University, writes in the introduction to the report. "New ways forward must be explored and seen as an opportunity to create a system that by design serves the health needs of us all—rich and poor."
Mar 30 ReAct report

Study finds high use of topical antimicrobials in Australian nursing homes

A national point-prevalence survey found that topical antimicrobials are frequently prescribed in Australian nursing homes, researchers reported yesterday in the American Journal of Infection Control.

To evaluate patterns of topical antimicrobial prescribing at Australian residential aged care facilities (RACFs), a team led by researchers from the University of Melbourne extracted all data submitted by RACFs in 2018 and 2019 to the National Antimicrobial Prescribing Survey. Data included the antimicrobial selection, start date, frequency, route of administration, therapy type, and indication. Antimicrobials were classified as topical if applied to skin or mucous membranes and included drops for eyes, nose, and ears.

The results showed that 4,277 of 52,431 residents at 629 RACFs were prescribed one or more antimicrobial, for a prevalence of 8.1% (95% CI, 7.9% to 8.4%). Of those residents, 1,500 were prescribed a topical antimicrobial (2.9%; 95% CI, 2.7% to 3.0%). Of all prescribed antimicrobials, 33% (1,614 of 4,899) were for topical application, mainly antifungals and antibacterials. The most frequently prescribed topical antifungals were clotrimazole (85.3%) and miconazole (9.1%), and the most frequently prescribed antibacterials were chloramphenicol (64.1%) and mupirocin (21.8%).

Tinea (38.3%) and conjunctivitis (23.8%) were the two most common indications. Topical antimicrobials were sometimes prescribed for pro re nata (as-needed) administration (38.8%) and for more than 6 months (11.3%). The review or stop date was not always documented (38.7%).

The study authors note that widespread use of mupirocin has been known to cause increased resistance rates in Staphylococcus aureus and that the widespread use of clotrimazole (86.4%) and chloramphenicol (95.1%) for tinea and conjunctivitis, respectively, is questionable. Based on their findings, they have recommended the implementation of some simple antimicrobial stewardship (AMS) practices at RACFs to improve prescribing of topical antimicrobials.

"It is recommended that those RACFs who need to develop or revise AMS policies and practices to improve topical antimicrobial use, do so using a multidisciplinary team based approach," they wrote. "Significant benefits in engaging all staff responsible for prescribing, dispensing and administration of antimicrobials is improved communication and coordination of care."
Mar 31 Am J Infect Control abstract

News Scan for Apr 01, 2021

News brief

Study: More stillbirths, maternal deaths during COVID pandemic

The first global assessment of the collateral impact of the COVID-19 pandemic on pregnancy outcomes found a significant increase in stillbirths, maternal deaths, maternal depression, and women requiring surgery for ectopic pregnancy, researchers reported yesterday in The Lancet Global Health.

The systematic review and meta-analysis, conducted by researchers in the United Kingdom, identified 40 studies and reports from 17 countries published from Jan 1, 2020, through Jan 8, 2021 that compared maternal and perinatal mortality, maternal morbidity, pregnancy complications, and intrapartum and neonatal outcomes before and during the pandemic. Studies and case reports of solely SARS-CoV-2-infected pregnant women were excluded.

Meta-analysis of 12 studies identified significant increases in stillbirth (pooled odds ratio [OR], 1.28; 95% confidence interval [CI],1.07 to 1.54), while two studies revealed an increase in maternal death (OR, 1.37; 95% CI, 1.22 to 1.53) during versus before the pandemic. Analysis of three studies found that Mean Edinburgh Postnatal Depression Scale scores were also higher during the pandemic than before, indicating poorer mental health (pooled mean difference, 0.42; 95% CI, 0.02 to 0.81). Three studies showed an almost six-fold increase in surgically managed ectopic pregnancies during the pandemic (OR, 5.81; 95% CI, 2.16 to 15.6).

Fifteen studies found no significant overall change in preterm births before 37 weeks (OR, 0.94; 95% CI, 0.87 to 1.02), while 12 showed a decrease in high-income countries (OR, 0.91; 95% CI, 0.84 to 0.99). In addition, two studies in high-income countries found a decrease in spontaneous preterm birth during the pandemic (OR, 0.81; 95% CI, 0.67 to 0.97). No overall significant effects were identified for other pregnancy outcomes.

Overall, outcomes were worse in low- and middle-income countries than in high-income countries.

"It is clear from our study and others that the disruption caused by the pandemic has led to the avoidable deaths of both mothers and babies, especially in low- and middle-income countries," lead study author Asma Khalil, MD, a professor of obstetrics and maternal fetal medicine at St. George's University Hospitals, said in a Lancet press release.

"We urge policymakers and health care leaders to prioritise safe, accessible, and equitable maternity care within the strategic response to the pandemic and aftermath, to reduce adverse pregnancy outcomes worldwide."
Mar 31 Lancet Glob Health study
Mar 31 Lancet press release

Varying risk factors for nursing home COVID infection, death revealed

Risk factors for COVID-19 infection in US nursing homes were related to county and facility rather than resident characteristics, while risk of hospitalization and death was linked to both facility and resident factors in a nationwide study published yesterday in JAMA Network Open.

Researchers from Johns Hopkins University and the University of Texas Medical Branch in Galveston studied coronavirus infections, hospitalizations, and deaths among 482,323 residents at 15,038 nursing homes from Apr 1 to Sep 30, 2020. The virus infected 28.4% of residents, of whom 21.3% were hospitalized, and 19.2% died within 30 days.

Facility-level traits were linked to 37.2% of the variation in risk of COVID-19 infection, while county characteristics accounted for 23.4%.

Resident-level risk of infection increased with rising body mass index (BMI) (eg, >45 vs 18.5 to 25 kg/m²: adjusted hazard ratio [aHR], 1.19) but seemed relatively unaffected by other individual traits. Risk of hospitalization also rose with increasing BMI (aHR, 1.40); male sex (aHR, 1.32); impaired functional status (aHR for severe vs unimpaired, 1.15); Black, Hispanic, or Asian race (aHR, 1.28, 1.20, and 1.46, respectively); and underlying illnesses (aHR, 1.21 and 1.16 for kidney disease and diabetes, respectively).

Risk of death climbed with age (aHR for ages 90 and older vs 65 to 70, 2.55); altered cognition (aHR for severe vs unimpaired, 1.79), and impaired function (aHR for severe vs unimpaired, 1.94). Mean resident age was 82.7 years, 67.8% were women, and 79.6% were White.

The researchers noted significant differences in risk of hospitalization compared with death. "This may represent resident preferences, triaging decisions, or inadequate recognition of death," they wrote.

Lead author Hemalkumar Mehta, PhD, said in a Johns Hopkins news release that the findings suggest that pandemic dynamics differed in nursing homes compared with the surrounding community during the pandemic. "The findings should help community leaders and nursing home administrators in devising better protections for nursing home residents during the remainder of the COVID-19 pandemic and in future pandemics," he said.

On a hopeful note, the authors pointed out that nursing home deaths plunged from 29.9% to 15.8% over the study period.
Mar 31 JAMA Netw Open study
Mar 31 Johns Hopkins news release

Earlier DRC Ebola outbreak relapse patient linked to 91 cases

A research team based in the Democratic Republic of the Congo (DRC) has documented an instance of Ebola relapse in a patient—which sparked a 91-case transmission chain—who had been vaccinated prior to the first infection. They detailed their investigation, which included genetic sequencing of the virus in the patient's first and second infection, today in the New England Journal of Medicine.

The patient was a 25-year-old man who worked as a motorcycle taxi driver who was sick during the DRC's recent large outbreak that spanned 2018 to 2020, the country's 10th and by far the largest. His first illness occurred in June 2019, about 6 months after he received the VSV-EVOV vaccine, which has been found to be highly effective. He received aggressive care, which included treatment with the mAb114 monoclonal antibody. His semen sample, tested 2 months later, was negative for the virus.

About 5 months after his first infection, he got sick again with Ebola and died after intensive treatment. A genetic analysis of virus from the man's first and second infection found that they differed by only two mutations, confirming that his second infection was a relapse. While symptomatic with the second infection, the man was in the community for 8 days and visited two health centers. Investigators found 29 cases that were linked to those exposures, with related cases that totaled 91 across six health zones over the next 4 months.

The authors said the case raises questions about the true efficacy of the vaccine, which studies suggest is 100%, and whether passive immunotherapy in rare instances could be associated with relapse. Also, they write that, though rare, relapse cases—as with sexually transmitted cases—should be noted as a potential transmission source.
Apr 1 N Engl J Med report

Global flu mainly sporadic, influenza B most common

Despite extra efforts to detect flu cases against the backdrop of the COVID-19 pandemic, global levels remained very low, according to an update from the World Health Organization (WHO) that covers the first half of March.

Some Northern Hemisphere countries, including India and Nepal, continue to report sporadic flu detections, with flu is at interseasonal levels in the Southern Hemisphere. Laos continues to report H3N2 cases, and some countries in western and eastern Africa have reported flu activity over recent weeks.

Globally, influenza B made up 64.8% of respiratory samples that tested positive for flu in the first half of March. And, of subtyped influenza A samples, 93.9% were H3N2.
Mar 29 WHO global flu update