Stewardship / Resistance Scan for Nov 08, 2019

Inappropriate hospital antibiotics for kids
Funding for gonorrhea drug candidate
Probiotic-associated bloodstream infections

Australian study: Improvement needed in antibiotic prescribing for kids

Nearly one in five antibiotic prescriptions for hospitalized children in Australia is inappropriate, Australian researchers reported yesterday in the Journal of Antimicrobial Chemotherapy.

The analysis of 4 years of data (2014 through 2017) from the National Antimicrobial Prescribing Survey (NAPS), an online auditing program that covers healthcare facilities in all Australian states and territories, found that among 6,219 prescriptions for 3,715 children in 253 facilities, 19.6% were inappropriate. For 35 facilities that entered data for all 4 years, appropriateness increased from 82.2% in 2014 to 85.3% in 2017, but without a statistically significant trend.

The most frequently inappropriately prescribed antibiotics were cefazolin, amoxicillin, and ceftriaxone. The most frequent reasons for antibiotic prescriptions being deemed inappropriate were "incorrect dose or frequency" or "spectrum too broad." Surgical prophylaxis was inappropriate in 59% of prescriptions.

Analysis of risk factors found that prescribing was more likely to be inappropriate for non-tertiary care facilities (odds ratio, [OR], 1.37; 95% confidence interval [CI], 1.20 to 1.55) and for non-metropolitan facilities (OR, 1.52; 95% CI, 1.30 to 1.77). Older age was significantly associated with inappropriate therapy, with children ages 3 to 12 having the highest risk (OR 6.2; 95% CI, 4.3 to 8.8). Prescriptions for children with a documented indication, children admitted to an ICU, and immunocompromised children were more likely to be appropriate.

The authors of the study conclude, "Almost 20% inappropriate prescribing for hospitalized children demonstrates room for improvement and this figure is higher in non-tertiary and non-major city settings, where fewer resources to support prescribing are available. Healthcare facilities need to work in partnership with governments and other organizations to support appropriate prescribing for children in all environments."
Nov 7 J Antimicrob Chemother study


New gonorrhea drug candidate receives funding boost

Swiss biopharmaceutical company Debiopharm said today that it has received second-phase funding from CARB-X (the Combating Antibiotic Resistant Bacteria Biopharmaceutical Accelerator) for development of a new antibiotic class targeting gonorrhea.

The $1.4 million in funding for Debio1453, an antibiotic development program based on compounds that target an enzyme essential to the growth of Neisseria gonorrhoeae, follows an initial award of $2.6 million from CARB-X in 2017. The second phase of the award was based on achieving targeted milestones.

"This continuation of research funding speaks to our antibiotic program's promising capacity to make a difference in the fight against drug-resistant N. gonorrhoeae," Debiopharm president Thierry Mauvernay said in a company press release.

The company says at the end of the second phase it will select the most suitable compound to enter into clinical trials for uncomplicated gonorrhea infections caused by susceptible and drug-resistant gonorrhea.

Because gonorrhea affects 78 million people worldwide and is becoming increasingly resistant to the last remaining treatment options, the World Health Organization (WHO) has deemed it a priority pathogen. WHO officials have warned that widespread treatment failure could emerge within the next few years if new antibiotics are not developed.
Nov 8 Debiopharm press release


Study describes probiotic-linked bloodstream infections in ICU patients

An epidemiologic and genomic investigation by US and Israeli scientists has found evidence of bloodstream infections in intensive care unit (ICU) patients linked to a widely used strain of probiotics.

In a letter published yesterday in Nature Medicine, researchers from Boston Children's Hospital, Walter Reed Army Institute of Research, and Technion-Israel Institute of Technology report that ICU patients at Boston Children's who were receiving Lactobacillus rhamnosus strain GG (LGG) probiotics had a markedly higher risk of developing Lactobacillus bacteremia than ICU patients who received no probiotics. Of the 522 patients who received LLG probiotics over a period of 5.5 years, 6 developed Lactobacillus bacteremia (1.1%), compared with only 2 of 21,652 patients who received no probiotics (0.009%). All 6 of the blood isolates from patients receiving the LGG probiotic were identified as L rhamnosus, while the 2 isolates from patients who didn't receive probiotics were identified as other Lactobacillus species.

Whole-genome sequencing further showed that all 6 of the L rhamnosus isolates and 16 isolates from probiotic capsules taken from the same batches given to the patients shared the same reference genome, suggesting high relatedness between the isolates. In addition, much of the genetic diversity among the L rhamnosus blood isolates mirrored pre-existing genetic diversity within the probiotic capsules.

However, the researchers also found genetic mutations in the blood isolates that did not appear in the isolates from the capsules, including one isolate with a mutation that confers resistance to the antibiotic rifampin, a finding that suggests within-host evolution of the probiotic.

"Probiotics have shown significant benefits for acute infectious diarrhea, antibiotic-associated diarrhea, and ulcerative colitis," the authors of the study write. "However, our findings highlight that as ICU patients have increased risk for probiotic-associated bacteremia, these potential benefits must be weighed against this risk when considering the continued use of probiotics in the ICU."
Nov 7 Nat Med study

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