Stewardship / Resistance Scan for Sep 16, 2020

News brief

Vaccine candidate fails to reduce C difficile infection in phase 3 trial

A phase 3 trial for a bivalent Clostridioides difficile toxoid vaccine was terminated because of futility, an international team of investigators led by scientists from Sanofi Pasteur reported yesterday in The Lancet Infectious Diseases.

In the observer-blind, randomized controlled trial, which was conducted in 326 hospitals in the United States, Canada, Latin America, Europe, and the Asia-Pacific region, adults 50 years or older with increased risk of C difficile infection were randomized 2:1 to receive one dose of Sanofi Pasteur's C difficile vaccine candidate (containing toxoids A and B) or one dose of placebo. The primary outcome was the efficacy of the vaccine in preventing symptomatic C difficile infection.

From Jul 30, 2013, through Nov 17, 2017, 9,302 participants were enrolled, with 6,201 in the C difficile vaccine group and 3,101 in the placebo group. The first planned interim analysis reported 34 C difficile infections over 11,697.2 person-years at risk (0.29 infections per 100 person years) in the vaccine group compared with 16 C difficile infections over 5,789.4 person-years at risk (0.28 infections per 100 person-years) in the placebo group, indicating a vaccine effectiveness of –5.2% (95% confidence interval [CI], –104.1% to 43.5%). Because of those results, futility was concluded and the trial was terminated

The safety analysis found that 2,847 of 6,113 participants (46.6%) in the vaccine group reported an adverse event within 30 days of injection, compared with 1,282 of 3,057 (41.9%) in the placebo group. The proportion of participants who had an adverse event leading to study discontinuation was 4.8% in both groups.

The investigators suggest several factors may have played a role in the vaccine not being effective, despite showing good immunogenicity. Among the explanations are that vaccination did not generate appropriate antibody function to effectively neutralize toxin in the intestinal environment. An aging or frail immune system and previous exposure to C difficile could also be factors, they said.

"In conclusion, although the candidate vaccine was immunogenic, it failed to reduce the incidence of symptomatic C difficile infection in participants at risk," they wrote. "The findings from this trial highlight the important challenges associated with the development of vaccines against bacterial nosocomial infections, and they will inform future vaccine development."

The trial was funded and designed by Sanofi Pasteur.
Sep 15 Lancet Infect Dis abstract


Study finds use of prior patient cultures linked to better empiric antibiotics

An intervention that alerted prescribers when antibiotic prescriptions were discordant with a patient's previous culture results was associated with improved empiric antibiotic prescribing at a tertiary care academic hospital, Canadian researchers reported yesterday in Clinical Infectious Diseases.

The intervention at Sunnybrook Health Sciences Centre in Toronto was a prospective audit-and-feedback intervention in which pharmacists provided early suggestions to prescribers when a patient's initial empiric antibiotic therapy was discordant with their most recent methicillin-resistant Staphylococcus aureus (MRSA) swab, previous cultures for extended-spectrum beta-lactamases (ESBLs), and most recent culture for a gram-negative (GN) organism. The researchers analyzed the impact of the intervention using a quasi-experimental design comparing the 9-month period before and after implementation.

Clinically significant discordance was identified 99 times in the pre-intervention period and 86 times in the intervention period. The proportion of patients who received concordant therapy increased from 73% (72/99) in the control group to 88% (76/86) in the intervention group (P = 0.01). The proportion increased in the MRSA subgroup from 86% to 93% (P = 0.39), in the prior GN subgroup from 50% to 83% (P = 0.069), and in the ESBL subgroup from 43% to 77% (P = 0.16) for the control and intervention groups, respectively.

The median time to concordant therapy was shorter in the intervention group (25 hours vs 55 hours; P < 0.001).

The authors of the study suggest the intervention should be further evaluated in large randomized clinical trials to determine if the changes in empiric prescribing affect clinical outcomes.
Sep 15 Clin Infect Dis abstract

News Scan for Sep 16, 2020

News brief

Contagious SARS-CoV-2 isolated from air in hospital patients' room

Live SARS-CoV-2, the virus that causes COVID-19, was isolated from air samples collected 2 to 4.8 meters (6.6 to 15.7 feet) away from two coronavirus patients—one recently released and one newly admitted—in a single hospital room, according to a study published yesterday in the International Journal of Infectious Diseases.

Aiming to add to the discussion about whether aerosols can contain infectious coronavirus, University of Florida at Gainesville researchers used new air samplers with a gentle collection process that is less likely than commonly used samplers to inactivate viruses. They were able to detect SARS-CoV-2 only when using the samplers without a high-efficiency particulate air (HEPA) filter on the inlet tube.

The researchers collected three 3-hour air samples from a room on a dedicated COVID-19 ward that was well ventilated, with six air exchanges per hour and triple-filter treatment of air returned to the room. They isolated the coronavirus from the air samples on cell culture and sequenced the genome.

The genome sequence of the isolated virus matched that of the newly admitted patient, who had not undergone any aerosol-generating procedures. The other patient had been transferred to a long-term care facility the night before the air samples were collected.

The authors said their findings show that, even in the absence of aerosol-generating procedures, COVID-19 patients can produce aerosols that can spread the virus farther than the 6 feet recommended in physical distancing guidelines.

"For aerosol-based transmission, measures such as physical distancing by 6 feet would not be helpful in an indoor setting, provide a false-sense of security and lead to exposures and outbreaks," the researchers wrote. "With the current surges of cases, to help stem the COVID-19 pandemic, clear guidance on control measures against SARS-CoV-2 aerosols are needed, as recently voiced by other scientists." 
Sep 15 Int J Infect Dis study


Surveillance, testing detect unnoticed COVID-19 cases at homeless shelters

Active surveillance and routine onsite testing could prevent the transmission of COVID-19 in homeless shelters, high-risk settings because of crowding, communal sleeping areas and shared bathrooms, University of Washington at Seattle researchers have found.

Their study, published yesterday in the Annals of Internal Medicine, involved testing 1,434 adult and pediatric residents and staff at 14 King County homeless shelters for COVID-19 infection from Jan 1 and Apr 24. This effort was part of a multiyear, cluster-randomized study of onsite testing and treatment for flu at homeless facilities started in November 2019.

Of the 1,434 people tested, 29 (2%) were positive for COVID-19 in five shelters. Most positive cases (21 [72.4%]) were identified during surge testing events rather than through routine surveillance, and 72.4% also had no symptoms. The 833 participants with symptoms were most likely to report a runny nose (43.0%), cough (37.3%), and muscle pain (23.7%).

Of the 725 people tested who had symptom-duration information, 40.3% had respiratory symptoms for less than 2 days at testing. Of all patients with positive test results, 31.2% met the case definition for influenza-like illness, while 12.7% met the criteria for coronavirus-like illness. Samples from 28 (2.1%) of participants tested positive for at least 2 of 17 tested respiratory pathogens, while 201 samples (15%) were positive for Streptococcus pneumoniae.

Those who tested positive for COVID-19 were more likely than those testing negative to be 60 years or older (44.8% vs 15.9%), and 86% of them slept in congregate spaces instead of private or smaller shared rooms.

Median participant age was 46 years (range, 0 to 82), and 67.9% of encounters in the shelters involved males, 40.9% involved whites and 30.5% involved blacks. Of all encounters, 57.7% involved smokers and 39.4% involved participants with one or more underlying medical conditions.

The authors said the findings indicate the need for routine COVID-19 testing outside of hospitals and clinics for the more than 560,000 homeless people in the United States. "Passive sentinel surveillance for respiratory viruses may only detect symptomatic cases severe enough to prompt health-seeking behavior and may miss milder ones, delaying the recognition of outbreaks and further viral spread," they wrote.
Sep 15 Ann Intern Med study


Children among latest DRC Ebola cases as outbreak grows to 123 cases

Two more Ebola cases were reported in the Democratic Republic of Congo (DRC) Equateur province outbreak, along with two more deaths, the World Health Organization (WHO) African regional office said today on Twitter. The developments lift the overall totals to 123 cases and 50 deaths.

The United Nations Office for the Coordination of Humanitarian Affairs (UN OCHA) said today in an update, posted on ReliefWeb, that a recent case was reported in a newly affected Ngelo Monzoi health area in the Bikoro health zone, raising the number of affected health areas to 40. It also said two infections in children were confirmed on Sep 14, one age 2 months and the other a 5-year-old.

Nearly 30,000 people have been vaccinated since the outbreak, the DRC's 11th involving Ebola, was first detected in early June.
Sep 16 WHO African regional office tweet
Sep 16 UN OCHA update


WHO: Global testing still finding very few flu positives

Flu is still circulating at lower levels expected for this time of year in both hemispheres, likely influenced by steps to reduce COVID-19 measures, the WHO said in its latest regular update.

Though the Southern Hemisphere's season typically runs from April through September, the season still hasn't started, and in the Northern Hemisphere, flu is below interseasonal levels. Sporadic detections were reported in some tropical countries, and Cambodia reported some H3N2 activity.

Globally, of about 140,000 respiratory samples tested during the last half of August at WHO-affiliated labs, only 34 were positive for flu. Of those, 19 were influenza A and 15 were influenza B. Of the subtyped influenza A viruses, all were H3N2.

In other flu developments, the WHO committee that recommends the strains to include the Southern Hemisphere's 2021 flu season began their online deliberations today, which are scheduled to wrap up on October 2. The group will also assess flu viruses that have pandemic potential to see if any new candidate vaccine strains are needed.
Sep 14 WHO global flu update
WHO flu vaccine strain selection committee background information

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