Long-acting lipoglycopeptides could be alternative step-down for serious bacterial infections, study finds

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A comparative effectiveness study suggests that long-acting lipoglycopeptide (laLGP) antibiotics could be an alternative step-down treatment for serious gram-positive bacterial infections, researchers reported yesterday in JAMA Network Open.

Using a target trial emulation framework, scientists from the University of New South Wales and the University of California-Los Angeles examined outcomes in patients who were hospitalized and discharged for serious bacterial infections—such as bloodstream infections, endocarditis, osteomyelitis, and septic arthritis—from October 2015 through October 2022 and received either laLGPs or standard-of-care (SOC) antibiotics. Although laLGPs (dalbavancin and oritavancin) are approved only for treating skin infections, they have shown promise as an alternative to outpatient parenteral antibiotic therapy (OPAT) for more serious infections, particularly in people who use drugs (PWUD), who may have difficulty adhering to OPAT.

The primary outcome measure was a composite of readmission, emergency department visit, and inpatient death or discharge to hospice within 90 days of the index admission. The outcome was analyzed in PWUD and non-PWUD populations.

Similar outcomes

Among 42,067 patients included in the analysis (median age, 61 years; 58.7% male), 5,047 (12.0%) were classified as PWUD, and laLGPs were prescribed in 825 (2.0%), including 241 PWUD (4.8%) and 584 non-PWUD (1.6%). Dalbavancin was the most common laLGP prescribed.

In the unadjusted analysis, PWUD patients in the laLGP group were less likely than those in the SOC group to meet the composite outcome within 90 days (44.4% vs 51.9%), as were non-PWUD patients in the laLGP group (31.7% vs 41.5%). In the adjusted analysis, there was no statistically significant difference in the composite outcome between the laLGP and SOC groups in both the PWUD (hazard ratio [HR], 1.01; 95% confidence interval [CI], 0.88 to 1.13) and non-PWUD (HR, 0.93; 95% CI, 0.86 to 1.00) participants, with similar findings across individual bacterial infections.

"This is an encouraging finding for the off-label use of laLGPs and adds to the evidence base supporting the effectiveness of laLGPs among PWUD and non-PWUD individuals," the study authors wrote, adding that randomized clinical trials are needed and that future research should compare patient and clinician preferences and cost-effectiveness.

Tool predicts progression to severe pneumonia in kids

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Stephanie Soucheray, MA

A new model developed through the international Pediatric Emergency Research Network (PERN) creates a predictive tool that will help clinicians decide if a child's pneumonia warrants hospitalization or intensive care, according to new findings in The Lancet Child and Adolescent Health.

Based on outcomes seen in 2,200 children ages 3 months up to 14 years old from 14 countries who sought care at emergency departments (EDs) for community-acquired pneumonia, the study classified which symptoms were predictive of more serious disease progression.

Overall, 58.1% of participants had mild, 36.5% moderate, and 5.4% severe disease. Runny nose and congestion were negatively associated with moderate to severe illness (adjusted odds ratio [aOR], 0.59; 95% confidence interval [CI], 0.46 to 0.76).

Chest retractions associated with severe disease

The symptoms most highly associated with severe pneumonia were hypoxemia (oxygen saturation 90% to 92%; aOR, 3.24) and chest retractions (aOR, 2.86). The model suggests that patients showing those signs should be admitted during ED visits, while children with any runny nose or congestion and no signs of respiratory distress can be treated at home.

While only a small percentage of children with pneumonia will have severe outcomes, it's crucial to identify these patients early.

"While only a small percentage of children with pneumonia will have severe outcomes, it's crucial to identify these patients early so clinicians can act swiftly and aggressively to prevent further deterioration in these children,” said lead author Todd Florin, MD in a press release from the Ann & Robert Lurie Children's Hospital of Chicago.

A predictive model based on the risk factors of symptoms showed good-to-excellent accuracy when compared to just clinician judgment alone in predicting illness severity.

"Once externally validated, our models will provide evidence-based information for clinicians to consider when evaluating pneumonia in children," said Florin.

Low-cost genome sequencing project to expand beyond COVID

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Chris Dall, MA

Scientists in the United Kingdom yesterday announced plans to expand use of a low-cost, real-time genome sequencing technique used to detect COVID-19 variants to cover a wider variety of pathogens.

Funded by Wellcome, the ARTIC 2.0 project will use an integrated, field-deployable viral sequencing system that was developed by scientists at the University of Birmingham and has been used by thousands of laboratories worldwide to look for COVID-19 variants of concern. The aim of ARTIC 2.0 is to further develop the "lab-in-a-suitcase" concept to conduct surveillance of viruses such as Ebola, mpox, and Marburg, as well as pathogens of unknown origin, and help public health officials respond to outbreaks more quickly and effectively.

The project will include researchers from the University of Cambridge and the University of Edinburgh and partners in the Democratic Republic of the Congo, Kenya, Ghana, Canada, and Switzerland. The Africa Centres for Disease Control and Prevention, Asia Pathogen Genomics Initiative, and World Health Organization International Pathogen Surveillance Network will help ensure the technology can be implemented worldwide.

"ARTIC 2.0 will help to realise the ambition that any laboratory, anywhere in the world could access affordable, high-quality genomic sequencing for their work," lead researcher Nick Loman, PhD, a professor of microbial genomics and bioinformatics at the University of Birmingham, said in a university press release. "With funding from Wellcome to develop ARTIC 2.0 we can develop a universal, global toolkit and learning platform that means any endemic virus or pathogen around the world can be sequenced quickly and cheaply."

Applying new compound to bed nets targets malaria parasites, not mosquitoes

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Mary Van Beusekom, MS

Baby girl under mosquito bed net — *World Bank, Arne Hoel / Flickr cc*

A Harvard University–based team has identified a chemical compound that, when applied to insecticide-treated bed nets, blocks malaria parasite transmission in mosquitoes without contributing to insecticide resistance.

Yesterday in Nature the researchers said that once-declining malaria death rates have recently stalled, partly due to widespread resistance of Anopheles mosquitoes to the insecticides used in long-lasting insecticide-treated nets (LLINs).

"One way to mitigate insecticide resistance is to directly kill parasites during their mosquito-stage of development by incorporating antiparasitic compounds into LLINs," they wrote. "This strategy can prevent onward parasite transmission even when insecticides lose efficacy."

Mosquitoes essentially disinfected

The researchers screened 81 chemical compounds with activity against the mosquito stages of the Plasmodium falciparum parasite, which causes malaria. Compounds were added to a dimethyl sulfoxide (DMSO)–acetone solution and directly pipetted onto the dorsal thorax of female Anopheles gambiae mosquitoes before infection with P falciparum.

The solution helped disrupt mosquito cuticle and enhance compound membrane permeability. Mosquitoes were then given a P falciparum–containing blood meal 7 days before the scientists counted oocysts (infectious parasite structures) in the digestive tract.

If an infected mosquito hits or lands on netting containing either of the ELQs, it's essentially disinfected.

Michael Rubal, PhD

Twenty-two compounds were active against the early parasite stages in the mosquito digestive tract, preventing infection. After using medicinal chemistry to boost the antiparasitic activity of the most effective compounds, the team produced several endochin-like quinolones (ELQs; small-molecule antimicrobials that disrupt cellular respiration in parasites) that were active against P falciparum.

The top two compounds killed 100% of the parasites when incorporated and/or extruded into net-like polyethylene (plastic) films at very low concentrations and retained activity for more than 1 year.

"If an infected mosquito hits or lands on netting containing either of the ELQs, it's essentially disinfected," coauthor Michael Rubal, PhD, of Southwest Research Institute (SwRI), said in an Oregon Health & Science University (OHSU) press release, "It absorbs the treatment via its legs, and that kills the parasites that it's carrying,"

In an SwRI press release, coauthor Michael Riscoe, PhD, of OHSU, said, "This emerging technology has great potential to impact efforts to control and eradicate malaria around the world."