Stewardship / Resistance Scan for Jun 08, 2020

News brief

Behavioral interventions tied to less urgent care antibiotic use

Implementation of behavioral "nudges" targeting non–guideline-concordant antibiotic prescribing helped reduce inappropriate prescribing for respiratory tract infections at three California urgent care centers (UCCs), researchers reported last week in Open Forum Infectious Diseases.

The study by researchers from Eisenhower Health, the University of California-Davis, and the University of Southern California Keck School of Medicine looked at prescribing rates for acute respiratory tract infections (ARTIs) at the high-volume rural UCCs before and after the implementation of three behavioral interventions: physician/patient education, public commitment, and peer comparison. The peer comparison intervention involved sending individual prescribing data and a blinded ranking email to providers.

The interventions were based on work from the MITIGATE study, which found that stewardship interventions tailored to the local site and setting reduced antibiotic prescribing for ARTIs by a third. An interrupted time series analysis (ITS) compared prescribing for ARTIs at the urgent care centers over a 16-month period before the intervention and 6 months during the intervention, a period that covered two flu seasons.

The analysis found a lower percentage of antibiotic-inappropriate prescribing during the intervention-period (58.5%) flu season (2018-19) than during the pre–intervention-period (73%) flu season (2017-18), resulting in an absolute 14.5% decrease in inappropriate prescribing for ARTIs, or about 981 prescriptions averted. The ITS analysis revealed that the estimated mean percent of antibiotic-inappropriate prescribing for ARTI decreased by 2.2% per month during the intervention period, compared with –0.71% during the pre-intervention period.

"The observed decrease in antibiotic-inappropriate prescribing for ARTI in this study suggests that utilizing a behavioral science approach may improve judicious use of antibiotics in community UCCs," the authors concluded.
Jun 6 Open Forum Infect Dis abstract

Higher US flu vaccine coverage linked to lower antibiotic prescribing

In another new study in Open Forum Infectious Diseases, researchers from the Center for Disease Dynamics, Economics & Policy in Washington, DC, and the University of Maryland School of Medicine in Baltimore found that increased influenza vaccination uptake was associated with state-level reductions in antibiotic use.

Using state-level monthly data on the number of dispensed antibiotic prescriptions from a large prescription drug database and seasonal flu vaccination coverage data from the Centers for Disease Control and Prevention's FluVaxView database, the researchers conducted a retrospective analysis of US flu vaccination coverage and antibiotic prescribing rates from 2010 through 2017. They used a fixed-effects regression analysis to analyze the relationship between vaccine coverage rates and the number of antibiotic prescriptions per 1,000 residents from January to March of each year. They also looked at the impact of vaccination on prescribing by age-group.

After controlling for access to healthcare, socioeconomic differences, vaccine effectiveness, climate, and state-level differences, the researchers found a significant negative association between increased influenza vaccination rates and antibiotic use rates.

A ten-percentage point increase in vaccine coverage was associated with 6.5% reduction in prescription rates, equivalent to 14.2 fewer antibiotic prescriptions per 1,000 individuals (95% confidence interval [CI], 6.0 to 22.4, P = 0.001). Increased vaccination coverage reduced prescribing rates in the pediatric population (0 to 18 years) by 6.0% or 15.2 prescriptions per 1,000 individuals (95% CI, 9.0 to 21.3; P < 0.001), and in those over 65 years by 5.2% or 12.8 prescriptions per 1,000 individuals (95% CI, 6.5 to 19.2, P < 0.001).

"Substantially boosting seasonal influenza vaccination coverage should be a central element of efforts to reduce use of antibiotics," the authors of the study wrote.
Jun 6 Open Forum Infect Dis abstract

News Scan for Jun 08, 2020

News brief

Ebola outbreak in second DRC outbreak rises to 12 cases

Twelve cases have now been reported in a new Ebola outbreak in northwestern Democratic Republic of the Congo (DRC), up from eight last week. The World Health Organization (WHO) confirmed in an email today that there are 12 cases in Equateur province, which includes 9 confirmed and 3 probable infections. Five deaths have been reported.

In other developments, genetic sequencing of a sample from the outbreak suggests that the emergence likely reflects a new spillover from animals to humans, according to findings from scientists at the National Institute for Biomedical Research (INRB) in Kinshasa posted on virological.org, a hub for prepublication data designed to assist with public health activities and research.

The outbreak, centered in Equateur province's Mbandaka health zone, is where a smaller outbreak was reported in 2018 that resulted in 54 illnesses, 33 of them fatal. The new event marks the DRC's 11th Ebola outbreak since 1976.

The country is still managing an outbreak in the eastern part of the country, where a 42-day countdown is underway until that outbreak is declared over on June 25 if no new cases are reported. That outbreak, which began in Augusto 2018, stands at 3,463 cases, 2,268 of them fatal, according to the WHO's online dashboard.
Jun 5 virological.org post
WHO online Ebola dashboard

Low COVID-19 diagnostic test sensitivity complicates containment, experts say

More attention should be paid to the high false-negative rates of COVID-19 diagnostic tests, according to a commentary published late last week in the New England Journal of Medicine.

False-positive results (testing positive when a patient doesn't have the disease) can lead to unnecessary quarantine and contact tracing, while false-negative results (testing negative in spite of having COVID-19) can lead to spread of the disease by infected yet asymptomatic people.

The US Food and Drug Administration (FDA) has issued Emergency Use Authorizations to test manufacturers, as well as guidance on test validation. As of Jun 1, no test manufacturer had reported results of clinical sensitivity assessments of their tests.

But the authors cite research studies that suggest a 70% sensitivity for available tests, which indicates the likelihood that the results will be negative for pathogens other than the novel coronavirus.

"At this sensitivity level, with a pretest probability of 50%, the post-test probability with a negative test would be 23%—far too high to safely assume someone is uninfected," they wrote. "Diagnostic testing will help in safely opening the country, but only if the tests are highly sensitive and validated under realistic conditions against a clinically meaningful reference standard."

They called for the FDA to require test manufacturers to detail their tests' clinical sensitivity and specificity at market authorization.

Because testing people who have no symptoms is urgently needed, the authors highlighted the importance of developing prediction rules for estimating the pretest probability of infection for both asymptomatic and symptomatic people to enable calculation of posttest probabilities after positive or negative results, as well as the development of thresholds for ruling out infection in different clinical situations.

"Negative results even on a highly sensitive test cannot rule out infection if the pretest probability is high, so clinicians should not trust unexpected negative results," they wrote. "It's possible that performing several simultaneous or repeated tests could overcome an individual test’s limited sensitivity; however, such strategies need validation."
Jun 5 NEJM commentary

VA study: Hydroxychloroquine does not cut ventilation risk for COVID-19

Another study, this one conducted at US Veterans Health Administration (VA) medical centers across the country, shows treatment with the antimalarial drug hydroxychloroquine—with or without the antibioitc azythromicin—did not reduce the risk for mechanical ventilation or death for COVID-19 patients. The study was published in the journal Cell.

To conduct the study, researchers looked at electronic health records from 807 people hospitalized with COVID-19 at VA medical centers across the country from Mar 9 to Apr 29. Among the COVID-19 patients, 395 patients did not receive hydroxychloroquine at any time during their hospitalization, 198 patients were treated with hydroxychloroquine, and 214 were treated with both hydroxychloroquine and azithromycin.

The risk of death from any cause was higher in the hydroxychloroquine group (adjusted hazard ratio [aHR], 1.83) but not in the hydroxychloroquine and azythromycin group (aHR, 1.31). Unadjusted rates of mortality at any time were 14.0%, 15.9%, and 15.7% for patients treated with hydroxychloroquine, hydroxychloroquine and azythromycin, and no hydroxychloroquine, respectively. Patients treated with hydroxychloroquine and azythromycin, or hydroxychloroquine alone also had longer hospital stays, by 38% and 33%, respectively.

"Among patients hospitalized with COVID-19, this retrospective study did not identify any significant reduction in mortality or in the need for mechanical ventilation with hydroxychloroquine treatment with or without azithromycin," the authors concluded.

The median age of patients seen in the VA medical centers was 70, 96% were male, and 66% had diabetes. The overall mortality rate was 19.3%.
Jun 5 Cell study

Previous-year flu vaccination does not lower protection, research finds

Getting revaccinated against the flu each year reduces the need for related medical attention, and previous-year vaccination does not appear to lower protection as some studies have shown, according to findings published yesterday in Clinical Infectious Diseases.

US Centers for Disease Control and Prevention (CDC) researchers and other public health experts analyzed the data of 31,819 participants in the US Influenza Vaccine Effectiveness Network who had an acute respiratory illness during the 2012-13 to 2017-18 flu seasons.

Overall, 12,517 participants (39%) were unvaccinated in both the previous and current flu seasons, while 2,839 (9%) were vaccinated in the preceding but not the current season, and 16,463 (52%) were vaccinated in the current season.

Across all flu types and subtypes, the authors said that current-season vaccination conferred added protection to those vaccinated in previous years for most seasons and that they found no significant loss in protection from current-season vaccination among participants also vaccinated the year before.

Vaccine effectiveness against any type of flu was, on average, 42% (95% confidence interval [CI], 38% to 47%) among participants vaccinated only in the current flu season, 37% (95% CI, 33% to 40%) among those vaccinated in both seasons, and 26% (95% CI, 18% to 32%) among those vaccinated only in the previous season, compared with those who were unvaccinated in both seasons.

Current-season vaccination lowered the odds of any type of flu among participants not vaccinated the previous season by 42%, including 57% against H1N1, 27% against H3N2, and 55% against influenza B. Current vaccination further reduced the odds of any type of flu infection among participants vaccinated the year before by 15%, including 29% against H1N1 and 26% against influenza B, but not against H3N2.

The authors said their findings support Advisory Committee on Immunization Practices recommendations that all people 6 months and older receive annual flu vaccinations. Despite the recommendations, the CDC estimated that only 63% of children and 45% of adults were vaccinated against the flu in 2018-19.
Jun 7 Clin Infect Dis abstract