Stewardship / Resistance Scan for Nov 06, 2019

News brief

Rapid viral testing in emergency department linked to lower antibiotic use

The results of a randomized clinical trial show that the use of a rapid, multi-pathogen respiratory panel (RP) in an emergency department (ED) was associated with a trend toward decreased antibiotic use, according to a study yesterday in Open Forum Infectious Diseases.

The trial, conducted by researchers at the University of California, Davis over 2 years, enrolled patients older than 12 months who visited a level 1 ED with symptoms of upper respiratory infection or influenza-like illness and randomly assigned them to receive either usual care plus rapid, multi-respiratory pathogen molecular testing or usual care alone. The primary outcome was antibiotic prescriptions, and secondary outcome included antiviral prescriptions, patient disposition, and length of stay.

Of the 191 patients enrolled in the trial, 93 were randomized to the RP group and 98 to usual care. Fifty-three (57%) of the patients in the RP test group had a virus detected and reported during the ED visit, compared with 7 (7%) in the usual care group; 20 patients (22%) in the RP group received antibiotics, compared with 33 (34%) of the usual care patients (-12 percentage points; 95% confidence interval [CI], -25 to 0.4). Nine of the patients in the RP group received antibiotics despite having a virus detected, but most either had a concomitant bacterial infection diagnosed clinically (8/9) or left the ED before test results were available (3/9).

A post-hoc analysis found that the reduction in antibiotic use was greater in children (-19 percentage points) versus adults (-9 percentage points). No differences were observed in antiviral use, length of stay, or disposition.

"The main effects of rapid RP testing in this study were to increase the proportion of patients with a lab-confirmed viral detection for clinical decision-making by 3-fold and reduce antibiotic prescription by about one third," the researchers write.

The researchers say that while the findings are limited by the small sample size, they suggest that the use of rapid viral tests in the ED could have benefits. They call for more research to determine whether specific groups are likely to benefit from testing and to evaluate the use of rapid diagnostics in combination with antibiotic stewardship strategies.
Nov 5 Open Forum Infect Dis abstract

CARB-X to fund novel gene-targeting antibiotic compounds

The Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator (CARB-X) today announced a milestone in its efforts to fund and promote early development of innovative antibacterial products.

CARB-X is awarding Techulon Inc., of Blacksburg, Virginia, $785,000 to develop a new class of antimicrobial compounds known as peptide-peptide nucleic acids (PPNAs), which target specific genes in drug-resistant pathogens that are essential for survival. The money will specifically fund development of PPNAs targeting the priority pathogens Acinetobacter baumannii and Pseudomonas aeruginosa, using Techulon's Rapidly Adaptable Nano Therapeutic platform.

The Techulon project is the 50th funded by CARB-X since it was established in 2016. The private-public partnership has awarded more than $150 million in non-dilutive funding to accelerate the development of new antibiotics, diagnostics, vaccines, and alternative treatments for drug-resistant bacteria.

"CARB-X is fighting the spread of drug-resistant bacteria by supporting the development of innovative therapeutics and other products that target the most serious bacterial threats. We are making progress," CARB-X Executive Director Kevin Outterson, JD, said in a press release. "The Techulon project is in the early stages of development but if successful and approved for use in patients, it could represent major improvements in the way deadly infections are treated."
Nov 6 CARB-X press release

Study backs use of aminoglycosides for ESBL bloodstream infections

Findings by Israeli researchers support the use of aminoglycosides as a possible treatment for bloodstream infections of urinary source caused by extended-spectrum beta-lactamase-producing Enterobacteriaceae (ESBL-EB).

In a study published today in the Journal of Antimicrobial Chemotherapy, the researchers retrospectively examined 193 patients at an Israeli hospital who had a positive blood culture for ESBL-EB and a positive urine culture with the same bacteria, as well as a clinical diagnosis of urinary tract infection, pyelonephritis, or urosepsis.

The patients were grouped according to the antibiotic treatment they received: aminoglycosides (108 patients) versus carbapenems (73 patients) or piperacillin-tazobactam (12 patients). The primary efficacy outcome was death from any cause at day 30, and secondary outcomes included recurrence of bacteriuria with the same bacteria in 90 days. The primary safety outcome was acute kidney injury (AKI) at 14 days.

Overall, 32 patients (16.6%) died, including 14 of 108 in the aminoglycoside group (13%) and 18 of 85 (21.2%) in the carbapenem and piperacillin-tazobactam groups. Risk factors for mortality included age, high Charlson comorbidity scores, presentation with severe sepsis or septic shock, and infection with bacteria other than Escherichia coli. Bacteriuria recurred in 48.8% of the aminoglycoside patients, compared with 44.7% of patients in the carbapenem and piperacillin-tazobactam patients.

After minimizing confounding, the scientists found that aminoglycosides were non-inferior to carbapenems or piperacillin-tazobactam regarding 30-day mortality (adjusted risk difference, 10.29%; 95% CI, -0.82% to 21.4%), and were also non-inferior in a subgroup of patients who presented without severe sepsis or septic shock. But aminoglycosides did not reach non-inferiority for bacteriuria recurrence (adjusted risk difference, -8.72%; 95% CI, -30.87% to 13.43%). AKI developed at a similar rate in both treatment groups: 12.0% versus 10.6%. Aminoglycosides were more efficacious in E coli infections.

The authors of the study conclude, "This approach supports avoiding excessive use of carbapenems without compromising efficacy and safety of treatment."
Nov 6 J Antimicrob Chemother study

News Scan for Nov 06, 2019

News brief

Respiratory virus sampling in India turns up human H9N2 avian flu

Researchers studying the incidence of respiratory syncytial virus (RSV) deaths in India's Maharashtra state earlier this year identified an H9N2 avian flu infection in a 17-month-old boy, according to a study published today in Emerging Infectious Diseases.

As part of a surveillance study in 93 villages, the team collected 2,085 nasopharyngeal swabs from children with severe or fatal pneumonia to test them for flu, RSV, and other respiratory pathogens. Low-pathogenic H9N2 viruses have a wide host range, and an earlier study in India suggested that 5% to 6% of people with direct exposure to poultry had H9N2 antibodies. However, confirmed human H9N2 infections have been reported only in Hong Kong, China, Bangladesh, and Pakistan.

A swab received by India's National Institute for Virology lab on Feb 12 tested positive by polymerase chain reaction for H9N2. The boy's symptoms, which included fever, cough, and shortness of breath, began on Jan 31, and a sample was obtained 2 days after he got sick. An investigation revealed he had gotten all of his routine childhood vaccinations. He had traveled with his family to a local religious gathering 1 week before his symptoms began. His father also became ill after the event, but migrant work kept him from getting tested. No direct exposure to poultry was found. The boy recovered uneventfully.

Whole genome sequencing of the H9N2 virus showed a mixed lineage of G1 and H732. Tests suggested that the virus was susceptible to adamantanes and neuraminidase inhibitors. Bayesian analysis suggested multiple introductions of H9N2 avian flu into Indian poultry.
Nov 6 Emerg Infect Dis report

Study highlights long-term effects of postop infections

A study that examined the long-term effects of postsurgical infections found that an infection in the first 30 days following surgery increased the risk of another infection within the following year and increased the risk of death. Researchers published their findings today in JAMA Surgery.

For the study, the team looked at data on people who had major surgery at Veteran's Health Administration facilities from January 2008 through December 2015. Of 659,486 patients, most were male, and the average age was 59.7 years. Overall, 3.6% had an infection in the 30 days after surgery. The most common infections were surgical site, urinary tract, pneumonia, and bloodstream. Findings revealed that 6.6% had a long-term infection, with urinary tract, skin and other soft tissue, bloodstream, and pneumonia most common. Of those with early post-surgical infections, 3.8% died during the 1-year follow-up period.

The investigators calculated that patients who had 30-day postoperative infections had a 3.2-fold higher risk of 1-year infection and a 1.9-fold higher risk of death compared with those who didn't have infections within the 30-day postoperative period. The authors concluded that cost-benefit calculations for surgical infection prevention programs should include the costs of long-term infection and death and that prevention steps targeting the 30-day postsurgical window may improve long-term patient outcomes.

In a related commentary, two experts from the University of Louisville wrote that much of the earlier literature focuses on 30-day morbidity and mortality. They note that the new report sheds light on prolonged consequences, with findings validated across a range of surgical specialties and infection types, independent of patient comorbidity. They hope, however, that future studies tease out other factors, such as inpatient status and postoperative infection type and mortality.
Nov 6 JAMA Surge abstract
Nov 6 JAMA Surg commentary

Philippines confirms 4th polio case

An outbreak of polio is growing in the Philippines, after the department of health confirmed the virus in another child, Xinhua reported today. This is the country's fourth case of the paralyzing illness.

The child is from Mindanao in the southern Philippines, but the exact location has not been confirmed by government officials, the story said. The department of health said a round of polio vaccination will begin this month in the area around Mindanao.

Until Sep 19, the Philippines had been polio-free for 19 years. The previous cases have been in children under the age of 5 and classified as poliovirus type 2.

Following the first case detection, the government launched a nationwide polio vaccine campaign, and health officials said that, as of Oct 31 more than 95% of children 0 to 59 months old have been vaccinated against the virus.
Nov 6 Xinhua news story