Stewardship / Resistance Scan for Nov 06, 2019

Rapid viral test and antibiotic use
CARB-X funding milestone
Aminoglycosides for ESBL blood infections

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

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