Paper highlights new universal flu vaccine tracking effort

A paper yesterday in Current Opinion in Virology highlights a new effort led by the Center for Infectious Disease Research and Policy (CIDRAP) to track the development of universal influenza vaccine technologies.

The paper, written by CIDRAP experts and other US and European scientists, provides an overview of the Universal Influenza Vaccine Technology Landscape, a database created in collaboration with the Global Funders Consortium for Universal Development (the Consortium) to compile, curate, and maintain information on universal vaccine technologies that have reached clinical or late preclinical stages of development.

In 2017, the Consortium and a large group of public- and private-sector stakeholders identified the need for a common landscape of investigational universal flu vaccine technologies to facilitate the assessment of research strategies, highlight knowledge gaps, and identify opportunities for informed and efficient investment.

The landscape currently profiles 22 technologies that have reached clinical development and 74 that have reached late preclinical stages. The strategies profiled are categorized by vaccine platform and are aimed at inducing neutralizing B-cell responses, cross-reactive T-cell responses, or a combination. Primary B-cell target antigens include the HA stalk region, neuraminidase, and matrix 2 membrane protein, and T-cell targets include internal proteins, such as nucleoprotein, matrix protein, and nonstructural protein. Routes of administration include intramuscular injection, intranasal, and transdermal approaches.

"The Universal Influenza Vaccine Technology Landscape provides a valuable tool for assessing the status of research on universal influenza vaccines, which are urgently needed to reduce the burden of seasonal influenza and mitigate the risk of pandemic influenza," the authors write. "Having access to up-to-date information on a wide range of experimental universal influenza vaccine technologies facilitates the identification of promising approaches and enables efficient monitoring of their progress through preclinical and clinical development."

CIDRAP is the publisher of CIDRAP News.
Apr 9 Curr Opin Virol paper

High-path H7N3 avian flu strikes South Carolina turkey farm

The US Department of Agriculture (USDA) Animal and Plant Health Inspection Service (APHIS) yesterday announced a highly pathogenic H7N3 avian flu outbreak at a commercial turkey farm in South Carolina's Chesterfield County. It said the event marks the first highly pathogenic avian flu outbreak in US poultry since 2017.

A few recent low-pathogenic H7N3 outbreaks had recently been reported in the area, including other turkey farms in two nearby North Carolina counties, and APHIS said the highly pathogenic strain apparently mutated from the low pathogenic strain circulating in the area. A similar pattern has been seen in poultry outbreaks before, including in the United States in recent years.

No human H7N3 cases have been reported and there is no immediate public health concern, APHIS said.

The affected flock showed increased mortality, and samples were first tested at the Clemson Veterinary Diagnostic Center and confirmed at the APHIC National Veterinary Services Laboratory in Ames, Iowa. Virus isolation is underway. The birds at the farm were culled to prevent the spread of the virus.

A notification from the World Organization for Animal Health (OIE) said the outbreak began on Apr 6 and that the virus killed 1,583 of 34,160 susceptible birds. It added that the facility has an epidemiological link to another South Carolina farm that experienced a low pathogenic H7N3 outbreak.
Apr 9 USDA APHIS statement
Apr 9 OIE report on high-path H7N3 in the United States

US flu activity continues to decline, CDC says

Laboratory confirmed influenza and influenza-like illness (ILI) activity in the United States continued to decline last week, according to today's FluView report from the Centers for Disease Control and Prevention (CDC). But ILI activity remains elevated, and the agency is still cautioning that the COVID-19 pandemic could be preventing people from seeking care as they normally would, which may affect the data.

The percentage of respiratory specimens testing positive for influenza at clinical laboratories fell from 2.1% to 0.8% the week ending Apr 4, while visits to clinics for ILI dropped from 5.2% to 3.9%, still well above the national baseline of 2.4%. The number of jurisdictions reporting high ILI activity decreased from 31 the previous week to 21, and the number of jurisdictions reporting regional or widespread flu activity declined from 41 to 31.

While flu severity indicators remain moderate to low overall, the cumulative hospitalization rate for the season increased again, from 67.9 hospitalizations per 100,000 population the previous week to 68.2 per 100,000 hospitalization. And the percentage of deaths attributed to pneumonia and influenza rose from 8.2% to 10%. The CDC says that increase is due to an increase in pneumonia deaths and likely reflects COVID-19 activity.

The CDC also reported 4 more pediatric deaths this season, bringing the total to 166, which is higher than most recent flu seasons but still lower than the 2017-18 season, when 188 child deaths were recorded. In addition, the hospitalization rate for children 0 to 4 years old is the highest the CDC has on record for this group, while the hospitalization rate for children 5 to 17 years old is higher than any season besides the 2009 H1N1 pandemic season.

Testing by public health laboratories shows that 57.1% of the influenza viruses circulating since Sep 29, 2019, are influenza A, and 42.9% are influenza B. The most common influenza A strain is 2009 H1N1 (92.6%), and the most common influenza B lineage is Victoria (98.4%).

The CDC estimates that so far this season there have been at 39 million flu illnesses, 410,000 hospitalizations, and 24,000 deaths. The agency says this is the final week of a full FluView report.
Apr 10 CDC FluView report

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

Study shows stewardship benefits of ID specialists

Originally published by CIDRAP News Apr 9

A retrospective study of Veterans Health Administration (VHA) hospitals found that the presence of an infectious diseases (ID) specialist may facilitate improvements in antibiotic prescribing, US researchers reported today in Clinical Infectious Diseases.

For the study, a team led by researchers from the Iowa City Veterans Affairs Health Care System evaluated antibiotic use among patients admitted to an acute-care bed at 122 VHA hospitals during 2016. They used data from a mandatory antibiotic stewardship survey completed by VHA hospitals to determine which hospitals had access to an ID-trained physician or pharmacist, and which had antibiotic stewardship programs.

They then compared antibiotic use among all patient admissions at ID sites with antibiotic use among patients at non-ID sites. Antibiotic use was quantified as days of therapy (DOT) per days-present, and was categorized based on National Healthcare Safety Network definitions.

Overall, 18 of the 122 hospitals (14.8%) lacked an on-site ID specialist. During 2016, there were 525,451 admissions at the ID hospitals and 23,007 admissions at the non-ID sites. In the adjusted analysis, which accounted for factors such as demographics, individual comorbidities, and severity of illness, the presence of an ID specialist was associated with lower use of broad-spectrum antibiotics (odds ratio [OR], 0.92; 95% confidence interval [CI], 0.85 to 0.99), higher narrow-spectrum beta-lactam use (OR, 1.43; 95% CI, 1.22 to 1.67), and lower total antibiotic use (OR, 0.92; 95% CI, 0.86 to 0.99).

"Core principles of antibiotic stewardship include selecting narrow-spectrum agents when feasible, using antibiotics only when necessary, and prescribing antibiotics for the shortest effective duration," the authors of the study write. "Based on our findings, it appears that at least some of these principles were more broadly applied to patients at hospitals with ID specialists."

The authors suggest that ID specialists may mediate changes in prescribing not only by recommending use of more narrow-spectrum agents and discontinuation of unnecessary antibiotic therapy, but also by enhancing institutional knowledge of appropriate prescribing and facilitating acquisition of stewardship resources.
Apr 9 Clin Infect Dis abstract

Antibiotics commonly prescribed for viruses in Scottish children

Originally published by CIDRAP News Apr 9

In another study today in Clinical Infectious Diseases, UK and Canadian investigators reported that nearly 14% of the antibiotics prescribed to Scottish children under the age of 5 from 2009 through 2017 were for illness caused by common viruses.

Using population registries, data on positive microbiology tests for viral pathogens, and details on community-dispensed prescriptions for antibiotics, the researchers set out to estimate the proportion of antibiotic prescriptions among children under 5 that were explained by virus circulation. Multiple respiratory pathogens were considered, including respiratory syncytial virus (RSV), influenza, human metapneumovirus (HMPV), rhinovirus, and human parainfluenza (HPIV) types 1 to 4.

Over the study period, 452,877 children received 6,066,492 antibiotic prescriptions, and 41,666 had positive viral respiratory tests before their fifth birthday. The overall antibiotic dispensing rate was 607.9 antibiotics per 1,000 child years.

Clear correlations in the patterns of antibiotic prescribing and circulating respiratory virus burden were observed. An estimated 6.9% of all antibiotics prescribed were for RSV, while 2.4% were attributable to influenza, 2.3% to HMPV, 1.5% to HPIV-1, and 0.6% to HPIV-3. A higher proportion of antibiotic prescriptions were attributed to these viruses among previously healthy children without high-risk conditions, compared with children with chronic conditions. Amoxicillin was the most commonly prescribed antibiotic, representing 61.9% of all antibiotics in the study.

The authors say that future vaccines, particularly an RSV vaccine, could substantially reduce antibiotic prescribing in children. "In the meantime, these results highlight critical targets for improving primary care practice and reducing unnecessary antibiotic use," they write.
Apr 9 Clin Infect Dis abstract

Data reveal resistance common in certain ocular pathogens

Originally published by CIDRAP News Apr 9

Antibiotic resistance and multidrug resistance is common in ocular staphylococcal isolates, particularly among older patients, according to a study today in JAMA Ophthalmology.

Using data from the ongoing Antibiotic Resistance Monitoring in Ocular Microorganisms (ARMOR) study, US researchers looked at clinically relevant isolates of Staphylococcus aureus, coagulase-negative staphylococci (CoNS), Streptococcus pneumoniae, Pseudomonas aeruginosa, and Haemophilus influenzae cultured from patients with ocular infections from January 2009 through December 2018. They assessed overall antibiotic resistance profiles, concurrent and multidrug resistance, and trends by age of patient and over time.

A total of 6,091 isolates from 6,091 patients were submitted from 88 US sites. Of these, 2,189 were S aureus, 1,765 were CoNS, 590 were S pneumoniae, 767 were P aeruginosa, and 780 were H influenzae. Overall, 765 S aureus (34.9%) and 871 CoNS (49.3%) isolates were methicillin resistant and more likely to be concurrently resistant to macrolides, fluoroquinolones, and aminoglycosides compared with methicillin-susceptible isolates (P < .001 for all). Multidrug resistance was also frequently observed among methicillin-resistant S aureus (577, 75.4%) and CoNS (642, 73.7%) isolates. Antibiotic resistance among S pneumoniae isolates was highest for azithromycin (214, 36.3%), whereas P aeruginosa and H influenzae isolates showed low resistance overall.

Small changes in antibiotic resistance were noted over time (less than 2.5% per year), with decreases in resistance to oxacillin/methicillin and other antibiotics among S aureus isolates, a decrease in ciprofloxacin resistance among CoNS, and an increase in tobramycin resistance among CoNS. Analysis of S aureus and CoNS isolates found an increase in antibiotic resistance with patient age.

The authors say the findings overall align with previous ARMOR reports and retrospective reviews of ocular isolates from US clinical centers. 
Apr 9 JAMA Ophthalmol study

Nursing home study finds mixed results for antibiotic time-outs

Originally published by CIDRAP News Apr 7

Despite an increase in the frequency of early discontinuation of broad-spectrum antibiotics, the use of an antibiotic time-out (ATO) in nursing homes in Wisconsin and Pennsylvania had mixed results overall, researchers reported today in Infection Control and Hospital Epidemiology.

To evaluate the impact of the ATO intervention, in which antibiotic prescriptions are assessed 48 to 72 hours after initiation, researchers from the University of Pittsburgh School of Medicine and the University of Wisconsin School of Medicine & Public Health collected data on 11 nursing homes over 25 months. They looked specifically at the effect of the intervention on the frequency and type of antibiotic change events (ACEs) and the extent to which initial antibiotic choice (broad- or narrow-spectrum) modified observed ACE patterns.

ACEs were categorized as early discontinuation, class modification, or administration modification. Analyses were performed using a difference-in-difference (DiD) approach.

Of 2,647 antibiotic events initiated in study nursing homes (1,498 in intervention facilities, 1,149 in control facilities, 376 (14.2%) were associated with an ACE. The overall proportion of ACEs did not significantly differ between intervention and control nursing homes. Early discontinuation ACEs increased in intervention nursing homes (DiD, 2.5%; P = .01), primarily affecting residents initiated on broad-spectrum antibiotics (DiD, 2.9%; P < .01). But the increase in early-discontinuation ACEs was offset by a reduction in class modification ACEs in intervention nursing homes.

The results are noteworthy because ATOs are one of the few antibiotic stewardship interventions that nursing homes can implement, yet few studies have looked at whether they have utility outside the hospital setting. The authors of the study say more research is needed.

"Although we did not observe the increase in ACEs in intervention nursing homes that we expected, we did find evidence that the ATO intervention did increase the frequency of early discontinuation ACEs," they write. "Consequently, we believe that our results justify further studies designed to isolate the effects of ATO interventions on the postprescriptive decision making by nursing home providers."
Apr 7 Infect Control Hosp Epidemiol abstract

Survey: High use of hospital antifungal stewardship strategies

Originally published by CIDRAP News Apr 7

In another study today in the same journal, the results of a survey show that use of antifungal stewardship strategies is high at hospitals within the Society for Healthcare Epidemiology of America's (SHEA) Research Network (SRN).

Of the 111 hospitals that received the survey, 45 (41%) responded, and 60% of those hospitals had large, well-established antibiotic stewardship programs (ASPs). In 43 hospitals, the ASPs used antifungal stewardship strategies, most commonly prospective audit and feedback (73.3%) led by a pharmacist, followed by prior authorization and restriction (67.4%). Roughly half of responding hospitals reported using education (47.0%) or creating guidelines for invasive fungal infection (IFI) management (51.1%).

Although the authors of the study hypothesized that larger and more well-established ASPs and hospitals caring for transplant patients would be more likely to use antifungal stewardship strategies, they found that there was a subset of respondents from private or community hospitals with small ASPs and no transplant populations, and they did not detect any significant associations among ASP size, ASP duration, presence of transplant populations, and higher likelihood of using antifungal stewardship strategies.

"In conclusion, we found that most hospital ASPs within the SRN have implemented antifungal stewardship strategies, including ASPs in smaller, nonacademic hospitals," the authors write. "Important areas for continued expansion of antifungal stewardship include education and institutional guideline development, implementation of rapid laboratory diagnostics, and surveillance of antifungal use with reporting to the NHSN [National Healthcare Safety Network]."
Apr 7 Infect Control Hosp Epidemiol abstract

Hospital prescribing algorithm shows promise, UK study finds

Originally published by CIDRAP News Apr 6

An algorithm designed to augment antibiotic prescribing in secondary care provided appropriate recommendations that were narrower in spectrum than current clinical practice, UK researchers reported in Clinical Infectious Diseases.

The Case-Based Reasoning (CBR) algorithm was developed using locally sourced data and designed for use in general medical and surgical settings at three London hospitals, with implementation and integration into the hospitals' clinical decision support systems starting in July 2017.

To evaluate the impact of the CBR algorithm on antibiotic prescribing, a team led by researchers with the UK's National Institute for Health Research examined two patient populations—patients with confirmed Escherichia coli bloodstream infections and general ward patients with a range of potential infections—and compared prescribing recommendations made by the CBR algorithm with those made by physicians in clinical practice.

Prescribing recommendations were evaluated using the Antimicrobial Spectrum Index (ASI) and the World Health Organization Essential Medicine List Access, Watch, Reserve classification system. The appropriateness of a prescription was defined as the spectrum of the prescription covering the antibiotic susceptibility profile of the known or most-likely organism.

A total of 224 patients (145 E coli patients and 79 general ward patients) were included in the study. Comparison of prescribing showed that 90% (202 of 224) CBR recommendations were appropriate, compared with 83% (186/224) of physician recommendations (odds ratio, 1.24; 95% CI, 0.392 to 3.936; P = 0.71), with similar results found in the specific analysis of E coli and general ward patients.

The CBR algorithm was associated with a significantly narrower spectrum of antibiotic prescribing, with a median ASI of 6 compared with 8 for physician prescribing. CBR recommendations were also more likely to be classified as Access class antibiotics (110/224, 49%) compared with physician prescriptions (79/224, 35%).

"A CBR algorithm provided antimicrobial recommendations that were in line with physician decisions, but also shifted recommendations towards narrower spectrum antimicrobial prescribing," the authors concluded. "Future work is now underway to explore the impact of integration of CBR with other methods for optimisation of antimicrobial prescribing, including dose optimisation platforms and patient-facing applications."
Apr 4 Clin Infect Dis abstract