Stewardship / Resistance Scan for Aug 05, 2020

News brief

NIH awards $19 million for new gonorrhea diagnostic test

The National Institutes of Health (NIH) today awarded $19 million for a new diagnostic test that can detect gonorrhea in under 30 minutes—and determine if the infection is susceptible to a single-dose antibiotic. The test is made by Visby Medical, Inc.

The award is part of the NIH's Antimicrobial Resistance Diagnostic Challenge, which aims to improve diagnostics for the more than 2.8 million antibiotic-resistant infections in the United States each year. Those infections kill more than 35,000 people annually, the NIH said in a news release.

"Challenge prizes spur innovation, and we saw many innovative concepts throughout this competition. I want to congratulate Visby Medical for their winning technology, which could help reduce the unnecessary use of antibiotics, a major driver of antimicrobial resistance," said NIH Director Francis S. Collins, MD, PhD.

Visby's device is a palm-sized, disposable test that allows clinicians to treat patients immediately with antibiotics likely to cure their infections.

Gonorrhea, one of the most common sexually transmitted infections in the world, has grown increasingly resistant to antibiotics in recent years. According to the Centers for Disease Control and Prevention, there were more than 580,000 US gonorrhea cases in 2018, a 63% increase from 2014.
Aug 5 NIH press release

Analysis finds Staph bacteremia mortality rises sharply after 2 days

A secondary analysis of patients with Staphylococcus aureus bacteremia suggests that the best cutoff to predict mortality is a duration of 2 days despite active antibiotic therapy, an international team of researchers reported yesterday in The Lancet Infectious Diseases.

In the largest study to date evaluating the risk associated with increasing duration of S aureus bacteremia, researchers with the International Staphylococcus aureus collaboration study group and European Society of Clinical Microbiology and Infectious Diseases Study Group for Bloodstream Infections, Endocarditis and Sepsis assessed outcomes on adults hospitalized for S aureus bacteremia at 17 European hospitals from January 2013 through April 2015. The primary outcome was 90-day mortality. The duration of bacteremia was defined as bacteremic days under active antibiotic therapy, counting the first day as 1.

Of the 1,588 patients assessed for eligibility, 987 were included in the analysis, with a median age of 65 years. Overall, death within 90 days occurred in 273 patients (28%). The 315 patients (32%) with more than 1 day of bacteremia had higher Charlson comorbidity index and sequential organ failure assessment scores and a longer interval from first symptom to first blood culture.

Analysis of the primary outcome found that crude mortality increased from 22% (148 of 672) with 1 day of bacteremia to 39% (85 of 218) with 2 to 4 days, 43% (30 of 69) with 5 to 7 days, and 36% (10 of 28) with more than 7 days of bacteremia. In addition, metastatic infections developed in 6% of patients (39 of 672) with 1 day of bacteremia compared with 13% of patients (40 of 315) who had bacteremia for at least 2 days. The second day of bacteremia had the highest hazard ratio and earliest cutoff significantly associated with mortality (adjusted hazard ratio, 1.93; 95% confidence interval, 1.51 to 2.46; P < 0.0001).

The findings are noteworthy because persistent bacteremia is poorly defined, and applied cutoff durations to define it vary from 2 days to more than 7 days.

"We believe that the second day of bacteraemia after starting active antibiotic therapy represents the most meaningful clinical cutoff to define persistent bacteraemia and to consider the implementation of additional diagnostic and therapeutic measures to reduce the high mortality in S aureus bacteraemia," the authors wrote.
Aug 4 Lancet Infect Dis abstract

Artemisinin resistance mutations detected in Rwandan malaria parasites

Researchers from Rwanda, France, and the United States have detected the emergence and expansion of an indigenous lineage of artemisinin resistant (ART-R) malaria parasites in Rwanda, according to a new study in Nature Medicine.

The researchers conducted an in-depth genetic analysis of Plasmodium falciparum samples collected at six Rwandan sites from 2012 to 2015 and performed gene-editing studies to evaluate the in vitro resistance phenotypes of parasites harboring mutations in the propeller domain of the Pfkelch13 gene, which can mediate artemisinin resistance. Resistance to artemisinin-based combination therapy (ACT) for malaria is widespread in Southeast Asia, particularly in the Greater Mekong Subregion, and has also been identified in Latin America, but to date has not been reported in Africa.

The scientists performed Pfkelch13 propeller domain genotyping on 534 pretreatment samples collected from patients who participated in clinical trials to assess the efficacy of artemether-lumefantrine and dihydroartemisinin-piperaquine for treating uncomplicated P falciparum malaria. While the cure rates in both treatment arms of these trials were above 95%, a Pfkelch13 R561H mutation—previously associated with delayed parasite clearance following ART monotherapy or ACT treatment in the Greater Mekong Subregion—was observed in 19 of 257 samples (7.4%) at the trial site in Masaka.

Gene editing using CRISPR-Cas9 confirmed the Pfkelch13 R561H mutation conferred artemisinin resistance in vitro, and phylogenetic analysis showed a clear separation between the Pfkelch13 R561H mutants found in Rwanda and those found in Southeast Asia and Latin America.

"This study clearly shows the early warning signs of ART-R in Rwanda," the authors wrote. "Genetic analyses indicate that Rwandan Pfkelch13 561H mutants are the product of de novo local emergence."

The authors add that if the spread of ART-R cannot be contained in Rwanda and neighboring countries, a rise in resistance to ACT partner drugs could result, leading to high treatment failure.
Aug 3 Nat Med study

News Scan for Aug 05, 2020

News brief

Ebola sickens 1 more in the DRC, 74 total, with 32 deaths

Testing confirmed 1 more Ebola case in the Democratic Republic of the Congo (DRC) Equateur province outbreak, raising the total to 74, the World Health Organization (WHO) African regional office said on Twitter today.

One more death was reported, raising the fatality count to 32, though it's unclear if it involved the latest confirmed patient.

The outbreak was first detected in early June and is the DRC's 11th Ebola event. Equateur province experienced a similar outbreak in 2018 that lasted only a few months and resulted in 54 cases and 33 deaths.

Health officials are worried about the current outbreak, because cases are spread across multiple health zones, including the provincial capital Mbandaka. Also, a number of confirmed cases are still in the community, raising the threat of further spread.
Aug 5 WHO African regional office tweet

Minority children in US shoulder large COVID-19 burden, research shows

COVID-19 infects a disproportionate number of US minority children and those of low socioeconomic status, mirroring trends observed in adults across the country, a study published today in Pediatrics has found.

Researchers from Children's National Hospital and George Washington University in Washington, DC, examined data from the first 1,000 patients aged 0 to 22 years with mild coronavirus symptoms and a physician referral at the pediatric hospital's walk-up/drive-through testing site from Mar 21 to Apr 28. (Of the total, 128, or 12.8%, were 18 or older.) Of the 1,000 children, 20.7% tested positive for COVID-19.

About 46% of Hispanic children (adjusted odds ratio [aOR], 6.3; 95% confidence interval [CI], 3.3 to 11.9) and 30% of black children (aOR, 2.3; 95% CI, 1.2 to 4.4) tested positive for coronavirus, versus only 7% of white children.

When the investigators used data from the American Families Survey to analyze the group by income level, 38% of children in the lowest-income group were positive for COVID-19, compared with only 9% of those in the highest-income group. Median family income differed by ethnicity, with white children's families earning a mean of $161,250 annually, versus black family incomes of $92,188, and Hispanic family incomes of $75,114.

Of the 10% of patients who reported contact with someone with COVID-19, about 33% were black, versus just 11% of whites.

The authors said the health disparities could be attributed to structural factors, limited access to healthcare, scarce resources, and bias and discrimination. For example, minorities are overrepresented in "essential" service industries that require face-to-face contact; are more likely than whites to rely on public transportation; have difficulty finding childcare in non-group settings; live in crowded, intergenerational settings; and may distrust the healthcare system and delay seeking care, raising the likelihood of spreading the virus to household members.

"Furthermore, symptomatic adults may avoid testing due to fears of deportation," the authors wrote. "Future work to ensure equitable allocation of testing and culturally appropriate prevention education may help improve early identification, quarantine, and distribution of resources to reduce community spread of disease."
Aug 5 Pediatrics study

Study: Few COVID-19 outbreaks, limited spread in Australian schools

Spread of COVID-19 in New South Wales, Australia, schools and childcare centers was low, according to an ongoing observational study published earlier this week in The Lancet Child and Adolescent Health.

The study, which began on Jan 25, involved analysis of virus transmission in 15 schools and 10 childcare facilities with COVID-19 cases. Twelve students and 15 adults tested positive for COVID-19. Of the 633 close contacts tested, 18 secondary cases were detected (attack rate, 1.2%); 5 of them (28%) were asymptomatic (3 infants, 1 teen, and 1 adult).

Three children and two adults were infected at three schools (attack rate, 0.5%). Nine of 10 childcare centers reported no secondary cases among 497 contacts, but one childcare center outbreak involved seven children and six adults (attack rate, 35.1%).

The authors cautioned that higher rates of transmission may occur in areas with more community spread or less stringent public health and community measures than in New South Wales but said that testing, contact tracing, quarantine, and school closures can help limit spread of the virus.

"With effective case-contact testing and epidemic management strategies and associated small numbers of attendances while infected, children and teachers did not contribute significantly to COVID-19 transmission via attendance in educational settings," they said. "These findings could be used to inform modelling and public health policy regarding school closures during the COVID-19 pandemic."

In a commentary in the same journal, W. John Edmunds, PhD, of the London School of Hygiene and Tropical Medicine, said that the findings may be of limited generality because most schools closed briefly after identification of a confirmed coronavirus case, and close contacts were expected to quarantine at home for 14 days after exposure.

"However, it is becoming increasingly clear that governments around the world need to find solutions that allow children and young adults to return to full-time education as safely and as quickly as possible," he wrote.
Aug 3 Lancet Child Adolesc Health study and commentary