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

UK trial finds azithromycin doesn’t reduce time to recovery from COVID

Treatment with azithromycin had little effect on reducing the time to recovery or risk of hospitalization in patients with suspected COVID-19, according to a randomized clinical trial published yesterday in The Lancet.

In the UK-based PRINCIPLE trial, which is investigating interventions against COVID-19 in those at risk of adverse outcomes, investigators randomly assigned people 65 years and older, or 50 and older with at least one comorbidity, who had been feeling unwell with suspected COVID-19 for 14 days to receive usual care plus azithromycin for 3 days, usual care plus other interventions, or usual care alone.

Of the 2,265 participants who enrolled from May 22 to Nov 30, 2020, 2,120 were included in the final analysis, with 500 in the azithromycin plus usual care group, 797 in the usual care plus other interventions group, and 823 in the usual care alone group. Eighty percent (402 of 500) of the patients in the azithromycin plus usual care group and 77% (631 of 823) of patients in the usual care alone group reported recovery within 28 days.

Using a Bayesian primary analysis model, the investigators found little evidence of benefit from azithromycin in the time to first reported recovery compared with usual care alone (hazard ratio, 1.08; 95% Bayesian credibility interval [BCI], 0.95 to 1.23), equating to an estimated benefit in median time to first recovery of 0.94 days (95% BCI 0.56 to 2.43).

Three percent of patients in both the azithromycin group and the usual care group were hospitalized (absolute benefit in percentage, 0.3%; 95% BCI -1.7 to 2.2), and no deaths were reported in either group.

Previous trials have found that azithromycin offers little to no benefit in hospitalized COVID-19 patients, but this is the first to examine azithromycin for COVID-19 in a community setting.

“In conclusion, our findings show that azithromycin should not be used routinely to treat COVID-19 in the community in older adults, in the absence of additional indications,” the study authors wrote. “These findings have important antibiotic stewardship implications during this pandemic, as inappropriate use of antibiotics leads to increased antibiotic resistance, and there is evidence that azithromycin use increased during the pandemic in the UK.”
Mar 4 Lancet study

Rapid, point-of-care test for respiratory infections could cut antibiotic use

Originally published by CIDRAP News Mar 4

A study today in the journal Family Practice reports that a rapid, multi-viral point-of-care test for respiratory infections was easy to use, acceptable to patients and clinicians, and appeared to influence clinical reasoning about antibiotics.

In the study, clinicians at four general practitioner (GP) practices in South West England used the BioFire Filmarray v1.7 test, which can detect 17 different types of respiratory viruses and three atypical respiratory bacteria from nose and throat swabs in around 65 minutes, on a sample of 93 patients older than 3 months who had suspected acute respiratory infections. Seventy-two percent of the samples were processed in less than 4 hours, and 90% in less than 24 hours. The median set-up time for each test was 2.7 minutes.

Of the 93 nose and throat swabs tested, 37% had no pathogens, 58% had at least one virus, and 2% had atypical bacteria. Pre-test, antibiotics were prescribed to 35% of patients with no pathogen detected and 25% of patients with a virus. Post-test diagnoses changed in 20% of patients, and the proportion of patients in whom clinicians’ diagnoses were certain or very certain increased after test use, particularly when a pathogen was detected.

Clinicians were also less likely to predict the patient would benefit from antibiotics post-test. Less than 10% of patients, however, were contacted after testing to change their treatment plan.

Interviews with clinicians, test processors, and administrators revealed that the test was easy to run and that clinicians liked it, but wanted quicker results and wanted more clinically relevant bacteria to be included. Overall, clinicians indicated they would reserve judgment until the test’s ability to support clinical management, improve outcomes, and reduce antibiotic use could be demonstrated in clinical trials.

“This was a small-scale feasibility study, and clinical trials are now needed to see if these point-of-care tests can safely and cost-effectively reduce antibiotic prescribing in primary care,” lead study author Alastair Hay, MD, a professor at the University of Bristol’s Centre for Academic Primary Care, said in a university press release. 
Mar 4 Fam Pract abstract
Mar 4 University of Bristol press release

Studies examine dental antibiotic prescribing in VA patients

Originally published by CIDRAP News Mar 3

Two studies yesterday in Infection Control & Hospital Epidemiology provide a snapshot of dental antibiotic prescribing among Veterans Affairs (VA) dental patients.

In one study, to establish a baseline for national antibiotic prescribing for acute oral infections prior to the release of the American Dental Association (ADA) 2019 guidelines, a team of VA researchers analyzed national VA data for 2017. They identified cases of three common acute oral infections—irreversible pulpitis (IP), apical periodontitis (AP), and acute apical abscess (AAP)—for which antibiotics are not recommended under the 2019 ADA guidelines, and included any antibiotics prescribed within 7 days of a dental clinic visit.

Of the 470,039 dental clinic visits in 2017, 12% of patients with IP, 17% with AP, and 28% with AAP received antibiotics. Although the median days’ supply of antibiotics for patients with a prescription was 7, prolonged antibiotic use was frequent: 42.5% of IP visits, 44.9% of AP visits, and 49.4% of AAP visits received antibiotics for more than 8 days. Multivariable logistics regression identified patients with high-risk cardiac conditions, prosthetic joints, and endodontic, implant, and oral and maxillofacial surgical procedures as more likely to receive antibiotics.

The study authors say that while guideline-discordant treatment was low, the findings may serve as a benchmark for future antibiotic stewardship efforts within the dental setting.

“The guideline-discordant antibiotic prescribing observed within the study may represent unnecessary antibiotic prescribing placing patients at increased risk of adverse events without providing any meaningful benefit,” they wrote.
Mar 2 Infect Control Hosp Epidemiol abstract

In the other study, some of the same researchers found that the rate of infection after getting teeth pulled was no different among VA patients who received antibiotics and those who did not.

Of 69,610 patients with dental extractions identified from 2017 national VA data, 404 were randomly selected for inclusion, and 154 (38.1%) received adjunctive antibiotics. An analysis of electronic health records found no difference in the frequency of post-extraction oral infection among those who did and did not receive antibiotics (4.5% versus 3.2%).

“These results suggest that antibiotics have a limited role in preventing postprocedural infection,” the authors wrote.
Mar 2 Infect Control Hosp Epidemiol abstract

CARB-X to fund vaccines for group A Streptococcus, Salmonella enterica

Originally published by CIDRAP News Mar 1

CARB-X announced today that it is awarding more than $10 million to GSK to develop vaccines to prevent serious infections caused by common bacterial pathogens that pose a significant health threat in the developing world.

Under the award from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator), GSK Biologicals and the GSK Vaccines Institute for Global Health (GVGH) will receive $8.2 million for a vaccine targeting group A Streptococcus and $2.2 million for a vaccine targeting Salmonella enterica infections. If both projects meet certain milestones, they could be eligible for an additional $8.2 million.

Group A Streptococcus causes strep throat, which affects an estimated 600 million people a year globally, but it can also cause more serious infections, like acute rheumatic fever, and pose more of a health threat in immunocompromised people. Salmonella enterica causes invasive nontyphoidal salmonellosis (iNTS) and typhoid fever, both of which are significant causes of morbidity and mortality in sub-Saharan Africa and low- and middle-income countries in other parts of the world.

The aim of the group A Streptococcus vaccine is to reduce the incidence and severity of strep A infections and autoimmune sequelae. The Salmonella enterica vaccine, which combines a recently licensed Typhoid Conjugate Vaccine with key antigens from other Salmonella strains that cause iNTS, aims to prevent deaths and contribute to reduced antibiotic consumption.

“As part of GSK’s overall Global Health approach, GVGH is dedicated to working with partners to develop effective and affordable vaccines that protect vulnerable communities against some of the most prevalent diseases causing high morbidity and mortality in developing countries,” GVGH Director Francesco Berlanda Scorza said in a CARB-X press release. “Thanks to CARB-X support, we have the opportunity to study and advance innovative vaccines against Salmonellosis and Group A Streptococcus, and contribute to the fight against antimicrobial resistance.”

Since its launch in 2016, CARB-X has awarded nearly $300 million for early-stage development of new antibiotic, vaccines, diagnostics, and other products that target drug-resistant bacteria.
Mar 1 CARB-X press release

VA study finds varying susceptibility in pneumonia-causing bacteria

Originally published by CIDRAP News Mar 1

A nationwide cumulative antibiogram for common bacterial isolates obtained from sputum samples shows some notable trends in susceptibility and resistance among pathogens that cause pneumonia, researchers in New York reported today in the American Journal of Infection Control.

To create the antibiogram, researchers from the Veterans Affairs (VA) Western New York Healthcare System obtained sputum culture data from patients treated at VA hospitals nationwide from 2009 to 2019. They calculated susceptibility percentages by dividing the total number of susceptible isolates of a particular bacterial species by the total number of reported isolates of that same bacterial species. Sputum and bronchial cultures from an average 10,345 VA patients per year were analyzed.

The results showed that the susceptibility of Streptococcus pneumoniae to third-generation cephalosporins rose from 92.2% to 95% over the study period, but azithromycin susceptibility fell from 56.8% in 2009 to 51.7% in 2018, and reduced susceptibility to erythromycin (59% to 46.2) and tetracycline (76.2% to 72.3%) was also observed.

Haemophilus influenzae maintained high levels of susceptibility to third-generation cephalosporins (99.7% to 97.2%), while third-generation susceptibility among Klebsiella pneumoniae trended upward (79.1% to 86.4%). Fluoroquinolone susceptibility among Escherichia coli remained low but stable (58% for ciprofloxacin and 57% for levofloxacin).

The authors say the findings suggest that, among VA patients, avoidance of macrolides (azithromycin and clarithromycin) for empiric treatment of community-associated pneumonia and avoidance of fluoroquinolones for empiric treatment of hospital-acquired or ventilator-associated pneumonia may be warranted based on the observed trends.

“Information obtained from this study can be used to help guide and improve empiric prescribing of antibiotics, which may in turn help reduce the development of antimicrobial resistance and lead to faster appropriate treatment of patients,” they write.
Mar 1 Am J Infect Control abstract