ASP Scan (Weekly) for Mar 12, 2021

News brief

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

NIAID awards grants for bacteriophage research

The National Institute of Allergy and Infectious Diseases (NIAID) announced yesterday that it has awarded $2.5 million in grants to support research on bacteriophage therapy.

Bacteriophages are viruses that can kill or incapacitate specific kinds of bacteria while leaving other bacteria and human cells unharmed. Scientists have been aware of the ability of bacteriophages to kill bacteria since 1917, but research withered after the discovery of antibiotics. Renewed interest has grown with the emergence of antibiotic resistance, and several case studies involving individual patients have demonstrated that bacteriophage therapy may be helpful in treating multidrug-resistant infections.

"In recent decades, multidrug-resistant bacteria, particularly those that cause potentially deadly diseases like tuberculosis, have become a serious and growing global public health concern," NIAID Director Anthony S. Fauci, MD, said in a National Institutes of Health (NIH) press release. "With these awards, NIAID is supporting research needed to determine if phage therapy might be used in combination with antibiotics—or replace them altogether—in treating evolving antibiotic-resistant bacterial diseases."

The NIAID grants will support bacteriophage research at 12 institutes. Among the projects being supported are a study characterizing different types of phages, a project exploring how phages combat biofilms, and a study examining optimum delivery methods for phages targeting Mycobacterium tuberculosis.
Mar 11 NIH press release

Higher nursing home use of certain antibiotics, COVID therapies noted

Originally published by CIDRAP News Mar 11

US nursing homes saw an increase in prescribing of antibiotics commonly used for respiratory infections during the pandemic, and large number of residents were prescribed drugs being evaluated for COVID-19 treatment, according to a study yesterday in Clinical Infectious Diseases.

For the study, researchers with the Centers for Disease Control and Prevention (CDC) looked at long-term care pharmacy data from 1,944 nursing homes in 48 states, assessing two categories of drugs: antibiotics and drugs that were being investigated for COVID-19 treatment, including hydroxychloroquine, famotidine, and dexamethasone. To account for seasonal variability in antibiotic prescribing and decreased nursing home occupancy during the pandemic, the researchers calculated the monthly prevalence of residents with a prescription dispensed per 1,000 residents from January to October 2020, then calculated the monthly relative percent change from 2019 to 2020.

From March to October 2020, prescribing of azithromycin and hydroxychloroquine per 1,000 residents was higher than 2019, most notably in April, when hydroxychloroquine prescribing was 563% higher (prevalence ratio [PR], 6.63; 95% confidence interval [CI], 5.87 to 7.48) and azithromycin prescribing was 150% higher (PR, 2.50; 95% CI, 2.37 to 2.63). Prescribing of these drugs declined in May 2020, but was still significantly higher than 2019 from July through October 2020. Prescribing of famotidine was 59% higher in April 2020 compared with 2019, while dexamethasone was 303% higher by July 2020.

In addition to azithromycin, prescribing of ceftriaxone was 43% higher in April 2020 versus 2019 and prescribing of doxycycline was 6% higher. Ceftriaxone use remained significantly elevated from May (+22%) through October 2020 (+11%) compared with 2019. But total antibiotic prescribing among nursing home residents was lower from May (-5%) through October 2020 (-4%) compared with 2019.

The study authors say the increases in prescribing of these drugs to nursing home residents without clear benefits are concerning, as they could put residents at greater risk for adverse events. They say further studies linking prescribing data to diagnoses and outcomes are needed to determine how appropriate these prescriptions were and what health impacts they had.
Mar 10 Clin Infect Dis abstract

Pew analysis shows antibiotic development pipeline remains thin

Originally published by CIDRAP News Mar 11

The latest analysis of the antibiotic development pipeline by the Pew Charitable Trusts shows there are still too few antibiotics in development to meet current and anticipated needs.

The analysis shows 43 antibiotics with the potential to treat serious bacterial infections were in clinical development as of December 2020, with 15 in phase 1 clinical trials, 13 in phase 2, 13 in phase 3, and 2 with new drug applications submitted to the Food and Drug Administration (FDA). Historically, only 1 in 5 infectious disease drugs that reach phase 1 studies will receive FDA approval, and roughly 60% of those that reach phase 3 will be approved.

At least 19 of the drugs in clinical development have the potential to treat gram-negative ESKAPE pathogens, which is a critical area of unmet need, and at least 15 have the potential activity against carbapenem-resistant/extended-spectrum beta-lactamase (ESBL)-producing Enterobacteriaceae, Acinetobacter baumannii, and Pseudomonas aeruginosa, which are considered high priority threats by the World Health Organization (WHO). At least 10 of the antibiotics, if approved, could address infections caused by drug-resistant Neisseria gonorrhea and Clostridioides difficile.

Only 10 drugs in the pipeline represent a novel antibiotic class or mechanism of action, according to Pew, and none are active against gram-negative ESKAPE pathogens or WHO critical-threat bacteria.

The analysis also found that only two of the companies with antibiotics in development rank among the top 50 pharmaceutical companies by sales, which is further indication that large pharmaceutical companies are abandoning antibiotic development.
Mar 9 Pew antibiotic pipeline analysis

Study links antibiotic order sets to improved ED prescribing

Originally published by CIDRAP News Mar 10

Use of antibiotic order sets built into the electronic medical record for common infectious diagnoses in the emergency department (ED) was associated with improved antibiotic prescribing at an academic medical center, Emory University researchers reported yesterday in Infection Control & Hospital Epidemiology.

The order sets at Emory University Hospital were created for cystitis, pyelonephritis, pneumonia, chronic obstructive pulmonary disease, and cellulitis and included recommended antibiotics based on clinical practice guidelines and a recommendation for the first dose to be given in the ED, along with a pre-populated prescription for appropriate duration.

The order sets were deployed in March 2019, and a survey was sent in November 2019 to assess whether the sets were being used. The researchers also conducted a chart review from October to November 2019 to assess the impact on prescribing practices for patients presenting with one of the five diagnoses.

While 59.4% of survey respondents said they used the order sets, the chart review showed that in 104 qualifying patient encounters, order sets were used in only 22 (21%). But patients were more likely to receive the first antibiotic dose in the ED when the order sets were used than when they were not used (90.9% versus 71.2%), and were also more likely to receive an appropriate antibiotic (86.4% vs 33.8%) and to have an appropriate duration prescribed (68.2% vs 24.5%). The researchers did not detect a statistically significant difference in appropriate renal dosing between the two groups.

Almost all providers who used the order sets noted they were easy to use and saved time.

The authors say larger studies are needed to evaluate the impact of order sets on prescribing and patient outcomes.
Mar 9 Infect Control Hosp Epidemiol study

CARB-X to fund development of Staphylococcus aureus vaccine

Originally published by CIDRAP News Mar 9

CARB-X today awarded up to $3.5 million to biotechnology company Affinivax, of Cambridge, Massachusetts, for preclinical development of a vaccine against Staphylococcus aureus infections.

The vaccine being developed by Affinivax, using its Multiple Antigen Presenting System (MAPS) technology, will include multiple staphylococcal protein antigens designed to elicit B cell antibody and Th17 and Th1 cell-mediated immune responses. It offers the potential for protection against mucosal colonization and invasive staphylococcal infections. Company leaders believe this approach could help them overcome hurdles that have thwarted other attempts at developing an S aureusvaccine.

"Data from our group and others support the view that, in addition to antibodies, Th1 and Th17 responses to S. aureus proteins are critical to achieve broad protection against this pathogen," Richard Malley, MD, scientific founder of Affinivax and a professor of pediatrics at Harvard Medical School, said in a CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) press release. "Our MAPS technology is ideally suited for this purpose."

S aureus can cause a range of disease, from minor skin infections to life-threatening bloodstream infections, and methicillin-resistant S aureus (MRSA) infections have limited treatment options. MRSA is labeled a serious threat by the CDC.

The project could be eligible for an additional $18.5 million in funding if it reaches certain development milestones.
Mar 9 CARB-X press release

Genomic analysis shows growth of resistance genes in diphtheria

Originally published by CIDRAP News Mar 8

Genomic analysis of Corynebacterium diphtheriae—the bacterium that causes the respiratory disease diphtheria—showed an increase in the average number of antimicrobial resistance (AMR) genes per genome per decade, UK and Indian scientists reported today in Nature Communications.

In the study, a team led by researchers from the University of Cambridge analyzed a collection of 502 C diphtheriae genomes that included 61 novel isolates from India, which has reported the highest number of diphtheria cases in the last few years, and 441 publicly available genomes. The isolates in the study covered 16 countries and territories and were collected over 122 years.

The analysis revealed that C diphtheriae is a genetically diverse species, with multiple distinct clonal populations circulating in the same geographic location, and that the more recently isolated genomes had a disproportionately high number of AMR genes, with a significant positive correlation between the average number of AMR genes per genome and the decade of isolation. Isolates collected from 2010 through 2019 had almost four times as many AMR genes as those collected in the 1990s.

The sulphonamide resistance gene sull was the common AMR gene detected and was found mainly in Indian isolates, along with aminoglycoside, chloramphenicol and trimethoprim resistance genes. Only one macrolide resistance gene was found, and no beta-lactam resistance genes were detected. This is noteworthy because erythromycin and penicillin are the traditionally recommended antibiotics of choice for early-stage diphtheria.

The study authors suggest the bacterium may be acquiring resistance genes in response to antibiotics exposure in the environment or during treatment for other bacterial infections.

In addition, the analysis found 18 different variants of the diphtheria toxin gene, which is the main virulence factor associated with the disease and is the target of the vaccine. Although diphtheria vaccines have been around for decades and remain effective, the number of cases reported globally has increased in recent years, and the authors say it's important to understand how the disease is evolving and spreading.

"We mustn't take our eye off the ball with diphtheria, otherwise we risk it becoming a major global threat again, potentially in a modified, better adapted, form," lead author Ankur Mutreja, PhD, of the Cambridge Institute of Therapeutic Immunology & Infectious Disease, said in a university press release.
Mar 8 Nat Comm study
Mar 8 University of Cambridge press release

COVID-19 Scan for Mar 12, 2021

News brief

Study notes moderate depression, anxiety in health workers during COVID

In a review of 65 studies from around the world, pooled data indicate that one in five healthcare workers (HCWs) have experienced moderate depression, anxiety, and/or post-traumatic stress disorder (PTSD) during the COVID-19 pandemic, according to a study published this week in PLOS One.

The study covered patients in 21 countries, most commonly in East Asia (46 studies, with 43 in China), the Middle East (7), and Europe (5). More than 97,000 HCWs were included, of whom 45% were nurses, 27% were physicians, 11% were other medical workers, and 1% were administration and support staff.

Across 55 studies that assessed depression, 21.7% of HCWs had moderate levels (95% confidence interval [CI], 18.3% to 25.2%), and across 57 studies that assessed anxiety, 22.1% had moderate levels (95% CI, 18.2% to 26.3%). Moderate PTSD was looked at in 9 studies, affecting 21.5% of HCWs (95% CI, 10.5% to 34.9%). Middle Eastern HCWs had the highest rates of moderate depression and anxiety (34.6% and 28.9%, respectively), which the researchers suggest could be from their high case burden.

Non-random sampling (which was employed in 60 of the studies) may have affected the results, the researchers note. The largest difference was found in anxiety: If using only randomly sampled studies, 7.9% of HCWs experienced anxiety, 14.2 percentage points lower than the total data.

Still, the researchers say, all values were higher than the pre-pandemic depression and anxiety levels that the World Health Organization reported in the general population (4.4% and 3.6%, respectively).

"The results of this review should inform action in policy and practice, to support the psychological wellbeing of health care workers," the researchers write. "Additional research should be conducted into the factors associated with poor mental health, and future prevalence studies must adopt random sampling methods to improve the precision of estimates."
Mar 10 PLOS One study

Low COVID-19 spread among children highlighted in 2 Spanish studies

With proper COVID-19 mitigations in place, schools may be able to open safely, according to two Clinical Infectious Diseases studies published today. Both studies took place in Barcelona province, Spain, with the first looking at 22 summer schools in Barcelona, and the second tracking 1,040 pediatric (under 16) COVID-19 cases in Catalonia.

In the summer school study, which ran from Jun 29 to Jul 31, 2020, 30 children under 15 and 9 adults were identified as index cases among 1,905 students and staff. Of 253 close contacts (median of 9 per case), 12 subsequent cases were identified, for a secondary attack rate of 0.3%. Comparatively, the general population's secondary attack rate was 1.9%.

"These results support current policies of school opening under strict preventive measures," the researchers write.
Mar 12 Clin Infect Dis summer school study

The second study focused its lens on whether household transmissions were more commonly from adult to child or vice versa. Of 1,040 children with COVID-19 from Jul 1 to Oct 31, 2020, 72.7% stemmed from an adult household member who had COVID-19; whereas, only 7.7% of children were confirmed index cases.

When children were the index cases, the researchers found that the secondary household attack rate was significantly lower during the school months versus the summer (21.0% vs 23.4%), and when compared with adult-transmitted cases (59.0% vs 67.6%). Overall, the study found that household viral transmission was 62.3% and that 47.2% of infected children were asymptomatic.

"Our results show that children, whether symptomatic or not, do not greatly contribute to household clusters of infection and are unlikely to be major drivers of the pandemic even when schools are open," the researchers conclude.
Mar 12 Clin Infect Dis household study

News Scan for Mar 12, 2021

News brief

NIAID awards grants for bacteriophage research

The National Institute of Allergy and Infectious Diseases (NIAID) announced yesterday that it has awarded $2.5 million in grants to support research on bacteriophage therapy.

Analysis of Guinea Ebola virus suggests link to survivor of earlier outbreak

The source of Guinea's latest Ebola outbreak might be a person rather than a fresh introduction from animals, according to an early analysis of genetic sequences posted today at Virological.org, a prepublication data hub.

Scientists found that the new Guinea genomes share 10 substitutions that accumulated during West Africa's 2014-16 outbreak, which they said make it unlikely that cases confirmed in recent weeks in Guinea reflect a new spillover from animals and are more likely linked to human cases in the region's earlier outbreak.

The investigators found that the new genomes diverge by only 12 to 13 substitutions, far fewer than what would be expected for sustained human-to-human transmission. "Therefore, the index case of the 2021 Guinea cluster was likely infected from a persistent source, such as via sexual transmission from an [Ebola] survivor," the team wrote, emphasizing that the findings are still preliminary. The researchers are from Guinea, the University of Edinburgh, and the University of Nebraska Medical Center.

At a World Health Organization (WHO) briefing today, Mike Ryan, MD, who leads the group's health emergencies program, said the WHO is aware of the findings, which raise new questions on the length of virus persistence and latency in humans. He added that the result is remarkable, given that a tiny proportion of Ebola survivors are thought to harbor the virus for 6 months or more and that the findings reinforce the need for survivor follow-up and support.

In other Ebola outbreak developments, the Democratic Republic of the Congo (DRC) added 1 more case to its total, which is now 12, including 5 deaths, according to the WHO's African regional office. The new case appears to be a probable infection involving someone who died in the community, the European Centre for Disease Prevention and Control (ECDC) said today in its weekly communicable disease threat report.
Mar 12 Virological.org post
Mar 12 WHO African regional office tweet
Mar 12 ECDC report

CDC ends investigation into 22-case multistate E coli outbreak

The US Centers for Disease Control and Prevention (CDC) said yesterday that its investigation into a multistate Escherichia coli O157:H7 outbreak is over, but the food source of the outbreak remains unknown.

The outbreak sickened a total of 22 people in seven states, resulted in 11 hospitalization and 1 death. There were no recalls linked to the outbreak. Since its previous update on Feb 2, officials confirmed 6 new cases and two newly affected states.

Affected states were Texas, Washington, Oklahoma, Arkansas, Virginia, Maryland and New York. Arkansas reported the most cases, with nine, and Oklahoma followed with six cases. The person who died was from Washington.

The earliest illness began on Dec 23, and the most recent symptom onset was Jan 12. Patient ages range from 10 to 95 years, and 68% were female. Of 20 people with information available, 11 were hospitalized. Of 18 people with information, 3 developed a type of kidney failure called hemolytic uremic syndrome.

State and local health officials interviewed people to see what they ate the week before they got sick, but no common exposure was ever identified.

"People reported eating a variety of food items, including leafy greens, broccoli, cucumbers, and strawberries. However, none of the food items were reported significantly more by sick people in this outbreak when compared to healthy people in the FoodNet population survey," the CDC said.

Whole-genome sequencing suggests the E coli from sick people is closely related and that they were probably sickened by the same type of food. Samples from 14 patients were resistant to chloramphenicol, streptomycin, sulfisoxazole, tetracycline, and trimethoprim-sulfamethoxazole. The CDC said the outbreak strain was previously linked to various sources, including romaine lettuce and recreational water.
Mar 11 CDC update
Feb 3 CIDRAP News scan on previous update

Six countries report more vaccine-derived polio cases

Six countries reported more polio cases this week, all involving circulating vaccine-derived poliovirus type 2 (cVDPV2), the Global Polio Eradication Initiative (GPEI) said in its latest weekly report.

Afghanistan reported 14 cases from eight provinces, putting its 2020 total at 308 and its 2021 number so far at 17. Tajikistan reported two cVDPV2 cases in the Districts of Republican Subordination, located in the central part of the country, putting its number for the year at three.

In Africa, Mali reported five more cases in three different towns, increasing its total for 2020 to 43. Sierra Leone also reported five new cases, four in the Western area and one in the Northern area, bringing its total so far to eight.

The DRC confirmed three additional cases, 1 in Tshuapa province and 2 in Equateur province, lifting its number for 2020 to 81. And Sudan reported 1 more cVDPV2 case, in North Darfur, totaling 58 for 2020.
Mar 11 GPEI update