The successful development of fenfluramine-loaded albumin nanoparticles paves the way for nasal administration of fenfluramine in drug-resistant epilepsy in children. Nasal administration would deliver the drug to the brain via the olfactory and trigeminal nerves and avoid significant hepatic metabolism to norfenfluramine which is cardiotoxic, explained Maxime Petit.

Successful nasal delivery of a drug depends on having a small volume and a prolonged residence time in the nasal cavity, to overcome mucociliary clearance. This calls for a formulation that combines a high concentration of the drug and a gelling agent or muco-adhesive.

In this study fenfluramine-loaded albumin nanoparticles were prepared and dispersed in an aqueous solution of pectin to make a final drug concentration of 10mg/mL. The particles were 107-135nm making them small enough to pass through the nasal mucosa. A stability study showed that 18.6% of the fenfluramine was released after three hours, indicating that the majority of the drug remained encapsulated. Local cytotoxicity (cell lysis) was assessed by measuring lactate dehydrogenase (LDH) release from a suitable cell line, as a model for nasal epithelium. The results showed that fenfluramine alone caused extensive cell lysis whereas with the nanoparticle formulation it was negligible.

The authors concluded that the sizes of the nanoparticles and the concentration of fenfluramine made the nanoparticle formulation suitable for therapeutic use. They plan to complete physicochemical studies before starting in vivo studies in mice.

Petit M et al. Development of fenfluramine in albumin nanoparticles for nasal administration. Short communication. GERPAC Congress 2025

Photo – Maxime Petit

A new study from the USC Caruso Department of Otolaryngology – Head and Neck Surgery, part of Keck Medicine of USC, published today in JAMA Otolaryngology – Head & Neck Surgery, is the first to link hearing aids and cochlear implants, surgically implanted devices that help those with profound hearing loss perceive sound, to improved social lives among adults with hearing loss.

“We found that adults with hearing loss who used hearing aids or cochlear implants were more socially engaged and felt less isolated compared to those who didn’t use them,” said Janet Choi, MD, MPH, an otolaryngologist with Keck Medicine and lead researcher of the study. “This suggests that hearing devices may help prevent the social disconnection and broader health consequences that can follow untreated hearing loss.”

Hearing loss affects an estimated 40 million American adults, yet many go untreated. When left unaddressed, hearing loss can make communication difficult, leading people to withdraw from conversations and social activities, according to Choi.

Previous research has shown that over time, social withdrawal can reduce mental stimulation and increase the risk of loneliness, anxiety, depression, cognitive decline and dementia. It has also linked chronic social isolation to biological and neurological changes, including increased brain inflammation and alterations in brain structure.

“Understanding the link between hearing loss, hearing device use and social isolation is crucial,” said Choi. “Until this study, it has been unclear whether hearing devices could help reverse the isolation.”

Choi and her fellow researchers conducted a comprehensive, systematic review and meta-analysis of 65 previously published studies, encompassing over five thousand participants, on how hearing aids and cochlear implants affect three key measures: social quality of life, perceived social handicap, which refers to the limitations and frustrations hearing loss can create in social situations, and loneliness.

The researchers found that adults using hearing devices feel more socially connected and less limited in social situations. They are better able to engage in group conversations and feel more at ease in noisy or challenging listening environments. Participants also reported feeling less socially handicapped by their hearing loss, with fewer barriers and frustrations during interactions and an improved ability to stay engaged without feeling excluded. This increased confidence can help users connect more easily with family, friends and colleagues, leading to stronger feelings of belonging and reduced social anxiety. The study also suggested hearing devices may reduce loneliness, although further research is needed in this area, according to Choi.

Those with cochlear implants reported the most improvement in their social quality of life. This is likely because cochlear implants offer greater hearing restoration than hearing aids, especially for individuals with more severe hearing loss. As a result, they may experience more noticeable improvements in social engagement once their hearing is restored.

While it was outside the scope of the study to measure how better social lives relate to improved cognitive outcomes, Choi believes there may be a connection, as previous research has found managing hearing loss may be key to reducing the risk of cognitive decline and dementia. “While our study didn’t directly measure cognitive outcomes, the improvements we saw in communication and social engagement suggest that by restoring clearer communication, hearing devices may help preserve cognitive health by keeping the brain more actively involved and people more connected,” Choi said.

This research follows a January 2024 study by Choi showing that adults with hearing loss who use hearing aids have an almost 25% lower risk of mortality, suggesting that treating hearing loss can improve lifespan as well as social quality of life.

“These new findings add to a growing body of research showing that hearing health is deeply connected to overall well-being,” said Choi. “We hope this encourages more people to seek treatment and helps clinicians start conversations with patients about how hearing devices can improve their quality of life.”

Published today in JAMA, the findings are based on data from three independent U.S.-based studies that focused on Puerto Rican and African American youths, who have higher rates of asthma and are more likely to die from the disease than their non-Hispanic white counterparts.

“Asthma is the most common chronic disease of childhood, and it disproportionately affects Black and Puerto Rican children, so it’s essential that we develop new therapies to better treat these young patients,” said senior author Juan Celedón, M.D., Dr.P.H., professor of pediatrics at Pitt and chief of pulmonary medicine at UPMC Children’s Hospital of Pittsburgh. “Because asthma is a highly variable disease with different endotypes, which are driven by different immune cells and respond differently to treatments, the first step toward better therapies is accurate diagnosis of endotype.”

Traditionally, asthma has been classified into endotypes known as T2-high or T2-low based on the amount of T helper 2 inflammation present. More recently, T2-low has been split into two endotypes: T17-high, which has less T helper 2 inflammation and more T helper 17 inflammation, and low-low, which has low levels of both types of inflammation.

Precise diagnosis of endotype usually involves genetic analysis of a lung tissue sample taken by a procedure called a bronchoscopy, which is done under general anesthesia. For children, especially those with milder disease, it’s not feasible or ethical to perform this invasive procedure, so clinicians have had to rely on imperfect tools, including immune markers in the blood, lung function and whether or not they have allergies.

“These tests allow us to presume whether a child has T2-high disease or not,” said Celedón. “But they are not 100% accurate, and they cannot tell us whether a child has T17-high or low-low disease. There is no clinical marker for these two subtypes. This gap motivated us to develop better approaches to improve the accuracy of asthma endotype diagnosis.”

Celedón and his team, including first authors Molin Yue, M.S., a Pitt graduate student, and Kristina Gaietto, M.D., M.P.H., instructor of pediatrics at Pitt, collected nasal samples from 459 youth across three different studies. Then they analyzed the expression of eight T2 and T17 signature genes.

As expected, analysis of nasal swab samples revealed a patient’s endotype. Across studies, 23% to 29% of participants had T2 high, 35% to 47% had T17-high and 30% to 38% had low-low endotype.

For treating severe T2-high asthma, there is a powerful new class of drugs called biologics, which target the immune cells that drive disease. However, no available asthma biologics directly target T17-high and low-low endotypes.

“We have better treatments for T2-high disease, in part, because better markers have propelled research on this endotype,” said Celedón. “But now that we have a simple nasal swab test to detect other endotypes, we can start to move the needle on developing biologics for T17-high and low-low disease.”

This rapid test for asthma endotype could also help push forward other areas of asthma research.

“One of the million-dollar questions in asthma is why some kids get worse as they enter puberty, some stay the same and others get better. Before puberty, asthma is more common in boys, but the incidence of asthma goes up in females in adulthood,” said Celedón. “Is this related to endotype? Does endotype change over time or in response to treatments? We don’t know. But now that we can easily measure endotype, we can start to answer these questions.”

Gustavo Matute-Bello, M.D., acting director of the Division of Lung Diseases at the National Heart, Lung, and Blood Institute, part of the National Institutes of Health (NIH) added, “Having tools to test which biological pathways have a major role in asthma in children, especially those who have a disproportionate burden of disease, may help achieve our goal of improving asthma outcomes. This research has the potential to pave the way for more personalized treatments, particularly in minority communities. More studies are needed.”

Other authors on the study were Yueh Ying Han, Ph.D., Franziska J. Rosser, M.D., M.P.H., Zhongli Xu, Christopher Qoyawayma, B.S.E., Erick Forno, M.D., M.P.H., and Wei Chen, Ph.D., all of Pitt and UPMC; and Edna Acosta-Perez, Ph.D., and Glorisa Canino, Ph.D., both of the University of Puerto Rico.

This research was supported by the NIH (HL079966, HL117191, HL150431, HL119952, UL1TR001857, HL129949, K08 HL159333 and HL149693).

This content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH.

Tonsillitis is a common reason for visits to the doctor and prescriptions of antibiotics in primary care. To determine whether a patient needs antibiotics, doctors use the so-called Centor Criteria for tonsillitis. The criteria include fever, tender and swollen lymph nodes in the angles of the jaw and inspection of the tonsils.

However, it has been unclear how well these criteria can be assessed during digital healthcare consultations compared to traditional in-person consultations. This lack of scientific evidence has become a growing concern as digital healthcare consultations become more common.

Digital vs physical assessment

The current study, published in the journal Infectious Diseases, examines whether digital assessments are as reliable as physical examinations in determining whether antibiotic treatment is warranted. The study includes 189 patients who sought care at healthcare clinics and urgent care clinics in Region Västra Götaland, Sweden, between January 2020 and October 2023.

Each patient in the study underwent two assessments: a digital medical assessment via video and a physical examination conducted by another doctor. The results show that digital healthcare consultations are not sufficient to assess some of the most important criteria, such as tonsil inspection and lymph node examination.

Digital not safe enough

One of the driving forces behind the study is Patrycja Woldan-Gradalska, a PhD student at Sahlgrenska Academy at the University of Gothenburg and a Resident Physician at Sätila Healthcare Clinic.

“Our study shows that although digital healthcare consultations are convenient for many patients, they are not reliable enough to assess tonsillitis. To ensure a correct diagnosis and treatment, it is still important to conduct a physical examination,” she says.

The authors are active in community medicine and public health at Sahlgrenska Academy at the University of Gothenburg and at Region Västra Götaland’s FoUUI primary and community healthcare, a support resource for research, education, development and innovation.

Current pertussis vaccines are widely used and effective at preventing whooping cough, caused by the Bordetella pertussis bacteria.  However, the vaccines fail to clear bacteria from the upper respiratory tract, allowing even vaccinated individuals to spread the disease.

The new vaccine combines the traditional pertussis antigens with an innovative adjuvant called T-vant, which boosts the body’s immune response specifically in the respiratory tract. In a study published in npj Vaccines, mice immunized intranasally with the new T-vant vaccine showed no signs of the bacteria in the lungs and nasopharynx – the upper throat area behind the nose – three weeks after infection. The bacteria remained prevalent in upper respiratory tract of mice that received the traditional vaccine intramuscularly.

“By developing a vaccine that can not only protect individuals but also prevent transmission, we hope to improve on existing vaccines and limit the spread of whooping cough in communities,” said lead study author Lisa Morici, professor of microbiology and immunology at Tulane University School of Medicine.

The T-vant adjuvant is derived from bacterial outer membrane vesicles, tiny particles that naturally stimulate the immune system. The study found that the adjuvant encouraged a mucosal immune response, spurring the activation of immune cells in the respiratory tract critical for halting the bacteria’s ability to colonize.

The study also found no adverse effects on lung tissue following immunization, highlighting the vaccine’s safety.

The findings are significant and come at a time when whooping cough cases are surging. Recent data from the Centers for Disease Control and Prevention showed a five-fold increase in U.S. cases over last year. The disease affects roughly 24 million people a year worldwide and primarily impacts infants and those with weakened immune systems.

A vaccine that can successfully prevent infection and transmission of whooping cough in humans could lay the groundwork for eliminating the disease altogether, said James McLachlan, co-author of the study and associate professor of microbiology and immunology at Tulane School of Medicine.

“These findings underscore the need for enhanced vaccines that can do more than just protect the individual,” McLachlan said. “We need vaccines that can effectively stop the bacteria from spreading within communities, and this new approach offers an encouraging step in that direction.”

T-vant was developed through support from the NIH Adjuvant Development Program. More information on T-vant can be found at https://vac.niaid.nih.gov/view?id=61.

The results of the ELVIS-Kids randomised controlled trial were presented by Professor Steve Cunningham from Child Life and Health, University of Edinburgh, UK.

He said: “Children have up to 10 to 12 upper respiratory tract infections, what we refer to as colds, per year, which have a big impact on them and their families. There are medicines to improve symptoms, such as paracetamol and ibuprofen, but no treatments that can make a cold get better quicker.”

ELVIS-Kids Chief Investigator Dr Sandeep Ramalingam, consultant virologist, NHS Lothian, Edinburgh, UK, had noted that salt-water solutions are often used by people in South Asia, as nasal irrigation and gargling, to treat a cold and wanted to explore if this clinical benefit could be replicated in a large study.

The research team recruited 407 children aged up to six years to a study where they were given either hypertonic saline ~2.6% (salt-water) nasal drops or usual care when they developed a cold. Overall, 301 children developed a cold; for 150 of these, their parents were given sea salt and taught to make and apply salt-water nose drops to the children’s noses (three drops per nostril, a minimum of four times per day, until well) and 151 children had usual cold care.

Professor Cunningham explains: “We found that children using salt-water nose drops had cold symptoms for an average of six days where those with usual care had symptoms for eight days. The children receiving salt water nose drops also needed fewer medicines during their illness.

“Salt is made up of sodium and chloride. Chloride is used by the cells lining the nose and windpipes to produce hypochlorous acid within cells, which they use to defend against virus infection. By giving extra chloride to the lining cells this helps the cells produce more hypochlorous acid, which helps suppress viral replication, reducing the length of the virus infection, and therefore the duration of symptoms.”

When children got salt-water nose drops, fewer households reported family members catching a cold (46% vs 61% for usual care). Eighty-two per cent of parents said the nose drops helped the child get better quickly and 81% said they would use nose drops in the future.

Professor Cunningham added: “Reducing the duration of colds in children means that fewer people in their house also get a cold, with clear implications for how quickly a household feels better and can return to their usual activities like school and work etc.

“Our study also showed that parents can safely make and administer nose drops to their children and therefore have some control over the common cold affecting their children.”

Professor Alexander Möeller is Head of the ERS Paediatric Assembly and Head of the Department for Respiratory Medicine at the University Children’s Hospital Zurich, Switzerland, and was not involved in the research. He said: “This is an important study that is the first of its kind to investigate the impact of salty nose drops in children with colds. Although most colds usually don’t turn into anything serious, we all know how miserable they can be, especially for young children and their families.

“This extremely cheap and simple intervention has the potential to be applied globally; providing parents with a safe and effective way to limit the impact of colds in their children and family would represent a significant reduction in health and economic burden of this most common condition.”

The team hope to further investigate the effect of saltwater nose drops on wheeze during colds, after initial results from this study showed that children who received the drops had significantly fewer episodes of wheeze (5% vs 19%).

Two in three parents say their child ages 5-12 uses personal audio devices, with half of parents of children ages 5-8 reporting elementary-aged kids use a device.

Among parents whose children use headphones and earbuds, half say kids spend at least an hour a day using them while one in six say a typical day for their child includes at least two hours of use, according to the University of Michigan Health C.S. Mott Children’s Hospital National Poll on Children’s Health.

“Over recent years we’ve mostly been concerned about teens overusing audio devices. But earbuds have become increasingly popular and prevalent among younger kids, exposing them to more intense noise on a regular basis,” said Susan Woolford, M.D., M.P.H., Mott pediatrician and co-director of the Mott poll.

“Noise exposure risks to young children have historically involved loud singular events like concerts or fireworks, but parents may underestimate the potential harm from excessive use of listening devices. It may be difficult to know whether their child’s exposure to noise is healthy.”

Children are most likely to use these devices at home, school and in the car, report findings show. About a fourth of parents also say children occasionally use audio devices on airplanes while less than 10% say kids use them on the bus, outside or in bed.

Half of parents agree that headphones or earbuds help keep their child entertained.

The American Academy of Pediatrics released a statement in 2023 on the need to reduce noise risks to children, with increasing evidence that children and teens may be more exposed through personal listening devices.

Prolonged or extreme exposure to high volumes of noise can result in long term health issues, including hearing loss or tinnitus, Woolford says.

“Young children are more vulnerable to potential harm from noise exposure because their auditory systems are still developing. Their ear canals are also smaller than adults, intensifying perceived sound levels,” Woolford said.

“Tiny hair cells inside the inner ear pick up sound waves to help you hear. When these get damaged or die, hearing loss is irreversible.”

Noise exposure among children can also affect their sleep, academic learning, language, stress levels and even blood pressure, she adds.

More parents of children aged 9-12 years than 5-8 years report their child uses headphones or earbuds and daily use was also more likely to be higher among the older age group, the poll suggests.

But only half of parents share they’ve tried to limit their child’s audio device usage, citing strategies such as asking the child to take a break, having set hours for use and using a timer.

Parents whose child uses headphones for more than two hours a day are also less likely to set time or volume limits, compared to parents who report less headphone use for their child.

Woolford offers four tips to reduce risks of noise exposure to children through headphones and earbuds:

Monitor volume levels

Parents can minimize the negative impact of audio device usage by monitoring and adjusting the child’s volume and time on devices, Woolford says.

She recommends parents follow the 60/60 rule – children should be limited to no more than 60 minutes of audio devices a day at no more than 60% of the maximum volume.

The sound level on listening devices that are less than 70 dBA (relative loudness of decibels heard) are very unlikely to cause noise-related damage.

“A good way to tell if an audio device is too loud is if a child wearing headphones can’t hear you when you’re an arm’s length away,” she said.

Parents can also limit their child’s risk by setting specific hours for audio device use or using a timer to keep track.

Use noise cancelling or volume limiting headphones

Parents should consider the risk of noise exposure when purchasing audio devices for their child by checking the information on device packages to identify products that limit the volume.

But some products marketed as “kid safe,” Woolford warns, do not limit the volume to 70 decibels.

However, children should avoid using noise-cancelling listening devices in situations when perception of sounds is crucial for safety.

“Noise-cancelling devices may help prevent children from increasing the volume to levels that are too high,” Woolford said. “But these devices shouldn’t be used when a child is engaged in activities where it’s important to hear their surroundings for their safety, such as walking or bike riding.”

Ensure kids take breaks from personal listening devices

Parents should help children intentionally have daily “device-free” time, Woolford says. This may involve putting away or locking the child’s audio devices when time limits are up.

They may also encourage kids to enjoy things like music on a low volume in their rooms instead of using earbuds to reduce noise intensity.

Personal audio devices should also be avoided when children are sleeping or at bedtime, Woolford says.

Be mindful of early signs of hearing loss

If parents feel their child may be at risk of hearing loss due to using audio devices, Woolford recommends checking with a pediatrician, an audiologist, or an ENT (ear, nose and throat) specialist.

“Early signs of hearing loss may include asking for repetition, hearing ringing noises often, speaking loudly to people nearby, delayed speech, or lack of reaction to loud noises,” Woolford said.

“Healthcare providers may be of assistance to parents by offering a simple explanation about hearing loss to help the child understand the reasons for limiting their use of audio devices.”

Published today in JAMA, the research letter points to a coming wave of supplychain disturbances if the Food and Drug Administration (FDA) moves to pull oral phenylephrine from the shelves, as recommended by an FDA advisory panel in 2023 that found the medication ineffective.

The researchers analyzed purchases of phenylephrine and pseudoephedrine—the only two nasal decongestants currently approved by the FDA—by pharmacies and major retail outlets. Between 2012 and 2021, American pharmacies purchased 19.8 billion units of phenylephrine products, compared to 13.2 billion units of pseudoephedrine products.

The researchers showed that pseudoephedrine is usually sold as a stand-alone product; phenylephrine, however, tends to be combined with several drugs and packaged as multi-symptom products. If the FDA opts to follow the advisory panel’s recommendation, most multi-symptom products will be pulled from the shelves, as there are still few pseudoephedrine-based alternatives on the market.

The study points to a need for continued reform of the over-the-counter drug review process, said lead author Timothy Anderson, M.D., M.A.S., a primary care physician, health services researcher and assistant professor of medicine at Pitt.

“The FDA needs to hold over-the-counter drugs to a standard of effectiveness similar to that of prescription drugs,” Anderson said. “A comparable pathway is needed for drugs that are sold over the counter as exists for post-approval monitoring of the risks and efficacy of prescription drugs. This will require a substantial investment in infrastructure to expand capacity.”

Other authors on the study were Katie J. Suda, Pharm.D., M.S. and Walid F. Gellad, M.D., M.P.H., both of Pitt; and Mina Tadrous, Pharm.D., Ph.D., of the University of Toronto.

This research was supported by the National Institute on Aging (K76AG074878) and the Canadian Institutes of Health Research (#202109).

“We found that adults with hearing loss who regularly used hearing aids had a 24% lower risk of mortality than those who never wore them,” said lead investigator Janet Choi, MD, MPH, an otolaryngologist and assistant professor of medicine at the University of Southern California Keck School of Medicine in Los Angeles. “These results are exciting because they suggest that hearing aids may play a protective role in people’s health and prevent early death.”

As background, the authors noted that hearing loss is a known factor for negative health outcomes and mortality. But to date it has not been established whether hearing aid use is associated with lower mortality.

The researchers evaluated data on 9,885 adults (age 20 years and older) who participated in the (USA) National Health and Nutrition Examination Survey between 1999 and 2012 and completed audiometry and hearing aid use questionnaires, revealing 1,863 adults with hearing loss.

Main measures included hearing loss, hearing aid use (never users, non-regular users, and regular users) and death (up to 2019).

Of the subjects with hearing loss, 237 were regular hearing aid users (i.e. wearing a hearing aid at least once a week, five hours a week or half the time) and 1,483 were never-users. Those wearing a hearing aid once a month or less were categorized as non-regular users.

The investigators reported a 24% difference in mortality risk between regular hearing aid users and never-users. This finding held even after adjustments were made for degree of hearing loss (from mild to severe), age, ethnicity, income, education other demographics and medical history.

They found no difference in mortality risk between non-regular users and never users, suggesting that occasional hearing aid use did not extend life.

The authors concluded, “Regular hearing aid use was associated with lower risks of mortality than in never users in US adults with hearing loss when accounting for age, hearing loss, and other potential confounders. Future research is needed to investigate the potential protective role of hearing aid use against mortality for adults with hearing loss.”

Acute sinusitis is one of the most common causes for children to be put on antibiotic medications, with patients in the United States filing nearly 5 million antibiotic prescriptions every year to treat the condition. The drugs amoxicillin and amoxicillin-clavulanate make up most of those prescriptions, but there is a lack of consensus on which should be first-line for children.

In a new study published today in JAMA and led by researchers at Brigham and Women’s Hospital, a founding member of the Mass General Brigham healthcare system, scientists analyzed the treatment outcomes of over 300,000 children who were prescribed either of the two drugs. They found that there was no difference in the rates of treatment failure — that is, having to go on a new course of antibiotics or seek additional treatment for sinusitis or complications — between patients prescribed amoxicillin and amoxicillin-clavulanate. Treatment failure was so rare, in fact, that the study’s authors say that physicians should be confident that either medication will clear a case of acute sinusitis that requires antibiotics. But the risk of adverse events, especially gastrointestinal symptoms and yeast infections, were higher among those prescribed amoxicillin-clavulanate.

“This study adds recent, actionable data and evidence to inform what antibiotic a clinician should choose to treat a child with acute bacterial sinusitis,” said lead author Timothy Savage, MD, MPH, MSc, an associate epidemiologist in the Brigham’s Division of Pharmacoepidemiology and Pharmacoeconomics. “As seen from this study, there’s no difference in the treatment failure rate regardless of which of these two antibiotics you choose.”

Amoxicillin-clavulanate is believed to treat a wider range of bacteria than amoxicillin, but it is also associated with more gastrointestinal side effects. Scientists also worry that in the long-term, overprescribing amoxicillin-clavulanate may accelerate the rate at which infectious bacteria develop antimicrobial resistance. Doctors have therefore wondered whether the benefits of prescribing amoxicillin-clavulanate to children with acute sinusitis outweigh the short- and long-term risks.

The researchers pulled data from 320,141 clinical cases of children diagnosed with acute sinusitis and compared whether children on amoxicillin or amoxicillin-clavulanate were more likely to undergo treatment failure. They discovered that there was no difference in the rates of treatment failures associated with either medication. Treatment failure in general was exceedingly rare; less than two percent of prescriptions failed, most of which were corrected by an outpatient medication change. Only 0.1% of children had failures so severe that they required a visit to the emergency room or hospitalization.

The clinical data showed that adverse events were somewhat rare but more frequent among patients treated with amoxicillin-clavulanate, occurring in 2.3% of patients treated with amoxicillin-clavulanate and 2% of patients treated with amoxicillin. Patients treated with amoxicillin-clavulanate had a 15% increased risk of gastrointestinal side effects and 33% higher risk of yeast infections compared to patients treated with amoxicillin. The study’s authors conclude that the more narrow-spectrum amoxicillin may be the best first-line choice to combat acute sinusitis.

“Our study shows that there are more adverse events when amoxicillin-clavulanate is used,” Savage said. “Based on these data, physicians should seriously consider prescribing amoxicillin as a first line of defense against acute sinusitis.”

Not all acute sinusitis cases are caused by bacterial infections; a previous study found that viruses may be responsible for up to 32% of instances. Still, because the symptoms of bacterial and viral sinusitis can be nearly indistinguishable, many doctors opt to first treat a patient with antibiotics and monitor whether the infection clears. Around 85% of children that present with acute sinusitis receive an antibiotic, with amoxicillin and amoxicillin-clavulanate accounting for 65% of those prescriptions. The current study did not include microbiologic data and the authors could not discern whether acute sinusitis diagnoses were due to viral or bacterial infections. As this was not a randomized clinical trial, the study authors also acknowledge the possibility that residual bias could have impacted the results, although they re-analyzed the data several different ways to try to mitigate this, with no difference in the results.

Two previous studies that compared clinical outcomes of the two drugs were conducted more than 20 years ago. Those analyses showed that both medications alleviated symptoms at similar rates, but both studies were limited by a combined sample size of under 300 patients. Bacterial species have evolved significantly in the last twenty years, a fact that convinced Savage and his team to launch a new, larger study comparing treatment failure rates of both drugs.

“If a physician is trying to decide between these two drugs, they can look at these results and see that 98% of kids got better regardless of whether they were prescribed amoxicillin or amoxicillin-clavulanate,” Savage said. “The chance that a child will end up in the hospital after using these drugs is less than one in a thousand. That should provide some reassurance that a child is going to do pretty well regardless of the antibiotic.”

Disclosures: Savage reports an institutional contract from UCB outside the submitted work, and co-author Krista Huybrechts reports institutional contracts from UCB and Takeda outside the submitted work.

Funding: This study was supported by the Eunice Kennedy Shriver National Institute of Child Health & Human Development (T32HD040128 and K08HD110600). The content is solely the responsibility of the authors and does not necessarily represent the official views of the National Institutes of Health. Dr. Savage had full access to all the data in the study and takes responsibility for the integrity of the data and the accuracy of the data analysis.

Paper cited: Savage TJ et al. “Treatment Failure and Adverse Events after Amoxicillin-Clavulanate vs. Amoxicillin for Pediatric Acute Sinusitis” JAMA DOI: 10.1001/jama.2023.15503

The researchers will present their results today at the fall meeting of the American Chemical Society (ACS). ACS Fall 2023 is a hybrid meeting being held virtually and in-person Aug. 13–17, and features about 12,000 presentations on a wide range of science topics.

A video on the research is available at www.acs.org/Earaches.

“We initially conceived of this idea by looking at the household cleaner bleach. Even though it has been used since the 19^th century, bacteria do not appear to have developed any widespread resistance to this cleaner,” says Rong Yang, Ph.D., the project’s principal investigator.

But Yang quickly warns that people should not treat infections with bleach. The solution sold at stores is highly concentrated and caustic, but when used in a properly controlled manner at extremely low concentrations, the active ingredient in bleach is considered compatible with living tissue.

After realizing that the active ingredient in the household cleaner could circumvent antibiotic resistance, the researchers, who are at Cornell University, decided to tackle a nearly universal childhood scourge: acute ear infections. These infections affect more than 95% of children in the U.S., and treatment typically requires taking antibiotics for five to 10 days. However, these regimens can cause problematic side effects, leading some families to discontinue the medication prematurely, particularly if symptoms resolve. But using these medications improperly can speed up the development of antibiotic resistance, which makes infections more difficult, if not impossible, to treat. This issue ranks among the biggest threats to global health, according to the World Health Organization.

Bacteria have more success fighting against some substances than others. Hypochloric acid from bleach belongs to a family of compounds, known as hypohalous acids, to which bacteria have yet to develop any significant resistance — most likely because of the numerous ways these highly reactive acids damage microbial cells, Yang says.

Because these substances break down quickly, Yang and her colleagues sought to generate one of them on an as-needed basis behind the eardrum in the middle ear, where ear infections occur. They found inspiration in an enzyme from giant kelp, which converts hydrogen peroxide (H₂O₂) to hypobromous acid (HOBr), a chemical relative of bleach.

A frequent cause of ear infections, the bacterium Streptococcus pneumoniae produces H₂O₂ to fight off other microbes. To mimic the kelp enzyme, which contains the metal vanadium, Yang and her colleagues designed nanowires made of vanadium pentoxide (V₂O₅). These produce HOBr only in the presence of the H₂O₂-producing bacteria, and their rod-like shape helps to keep them in place by reducing their ability to diffuse into body fluids.

In tests on chinchillas, which contract ear infections from the same pathogens as human children, they succeeded in eliminating most of the S. pneumoniae. Yang and colleagues found that after treatment with the nanowires, the animals’ once-inflamed eardrums returned to normal. Meanwhile, tests in healthy animals found evidence that the treatment did not interfere with hearing.

For these experiments, the researchers injected the nanowires directly into the middle ear. In more recent work in chinchillas, they developed a less invasive, more practical method for delivering the wires. By decorating the nanowires with peptides known to transport small particles across the eardrum, Yang and her team found they could deliver the treatment topically as a gel deposited into the ear canal. Once the gel was applied, the nanowires within it went through the intact tissue. They are also exploring other approaches for passing the nanowires through the eardrum.

Because other ear-infection-causing bacteria do not produce H₂O₂, the researchers are currently examining whether this system is effective in the presence of microbes other than S. pneumoniae, and how they might adapt it to fight the other bugs.

The researchers have not yet done studies to determine how long the system stays in place, although their evidence suggests the nanowires drain out of the middle ear after the infection clears. However, Yang suspects they could adapt the nanowires’ properties to stay in place for long periods afterward. This latter approach could make it possible to prevent recurrent infections that plague many children.

“If the bacteria return, the system could restart, so children wouldn’t need antibiotics repeatedly and breed more resistance along the way,” Yang says.

The researchers acknowledge support and funding from the National Institute on Deafness and Other Communication Disorders.

This research was presented at a meeting of the American Chemical Society.

“Five million kids in the U.S. get prescribed antibiotics for sinusitis each year,” said lead author Nader Shaikh, M.D., pediatrician at the University of Pittsburgh Medical Center and professor of pediatrics and clinical and translational science at the university. “Our study suggests that only half of these kids see an improvement in symptoms with antibiotic use, so by identifying who they are, we could greatly reduce unnecessary antibiotic use.”

Between February 2016 and April 2022, the investigators enrolled 515 children aged 2 to 11 who had been diagnosed with acute sinusitis based on clinical criteria.

The researchers took swabs from inside the nose, like a COVID-19 test, from each child and tested them for the three main types of bacteria involved in sinusitis.

The trial was designed to determine whether symptom burden differed in subgroups testing positive for nasopharyngeal Streptococcus pneumoniae, Haemophilus influenzae, or Moraxella catarrhalis on bacterial culture and by the presence of colored nasal discharge.

The subjects received oral amoxicillin (90 mg/kg/d) and clavulanate (6.4 mg/kg/d) (n = 254) or placebo (n = 256) for 10 days.

The primary outcome was symptom burden during the 10 days after diagnosis.

Most of the 510 subjects were aged 2 to 5 years-old (64%).

Using standard testing, the investigators reported that mean 10-day symptom scores were lower among the subjects in the amoxicillin/clavulanate group compared with those in the placebo group

Length of time to symptom resolution was lower for subjects in the antibiotic group (7.0 days) than in the placebo group (9.0 days).

Subjects who tested positive for bacteria achieved a better resolution of symptoms with antibiotic treatment then those who did not have bacteria, suggesting that testing for bacteria might be a simple way to detect children who could benefit from antibiotic treatment and avoid giving antibiotics to children who won’t.

“If antibiotics aren’t necessary, then why use them?” said Shaikh. “These medications can have side effects, such as diarrhea, and alter the microbiome, which we still don’t understand the long-term implications of. Overuse of antibiotics can also encourage antibiotic resistance, which is an important public health threat.”

The authors concluded, “In children with acute sinusitis, antibiotic treatment had minimal benefit for those without nasopharyngeal bacterial pathogens on presentation, and its effects did not depend on the color of nasal discharge. Testing for specific bacteria on presentation may represent a strategy to reduce antibiotic use in this condition.”