Bob Kronemyer

According to Mark R. Schleiss, MD, a professor of pediatrics at the University of Minnesota Medical School in Minneapolis, some clinicians tend to overprescribe antibiotics for children, both in inpatient and outpatient settings, for a range of viral ailments.

“I am alarmed about the overprescribing of antibiotics, and clearly the pandemic has thrown gasoline on this fire,” he said.

The overprescription of antibiotics can have life-threatening consequences, including the emergence of 

 infection and severe allergic and anaphylactic reactions to antibiotics.

“The biggest issue, however, is that antibiotic overuse promotes emergence of antibiotic-resistant strains of bacteria that can cause disease, particularly in children with underlying health issues, and we are left—quite literally—with no available therapies to help these children,” Schleiss noted.

A recent policy statement from the American Academy of Pediatrics (AAP) points to growing evidence that antibiotic stewardship programs can reduce antibiotic overuse and still improve patient outcomes

“I strongly support the AAP statement,” Schleiss said. “We must recognize, though, that overprescription of antibiotics in children is a multifaceted problem; other stakeholders, including our colleagues in internal medicine, public health, and the pharmaceutical industry, must work together to find solutions.”

Schleiss noted there are efforts to develop new antibiotics for bacterial infection, due to the fact that bacteria is so resistant to antibiotics. “However, we must acknowledge that administration of new antibiotics is no substitute for being more judicious with antibiotic use in general,” he said.

The therapeutic use of bacteriophages—small viruslike structures that can destroy bacterial pathogens—represents a highly innovative antibacterial intervention that might someday obviate the need for traditional antibiotics, Schleiss said.

In addition, research into the human microbiome and strategies aimed at restoration of these “normal” bacteria help fight infection by limiting the emergence of pathogenic organisms.

“We also know that annual influenza vaccination can reduce unnecessary antibiotic use, but uptake of this vaccine among children remains low,” Schleiss said. “As [coronavirus disease 2019] immunizations work their way into pediatric use, use of this vaccine is predicted to ameliorate overprescription of antibiotics.”

Ateev Mehrotra, MD, MPH, an associate professor of health care policy and medicine at Harvard Medical School in Boston, Massachusetts, said the pandemic has definitely reduced antibiotic prescribing in children. “However, we are still reviewing the data to see the full effect,” he said.

The most fundamental change that Mehrotra’s data and other data indicate is a dramatic decrease in the number of children becoming sick due to acute respiratory illnesses.

 “With all the pandemic precautions, schools have been shut down and kids are staying home, therefore significantly reducing transmission,” Mehrotra said. “This is important because acute respiratory illnesses account for the vast majority of antibiotics for children.”

Mehrotra said it is hard to predict if the decrease in antibiotic prescribing will persist once the pandemic subsides. “Only time will tell,” he said. “But if there is any take-home message from the pandemic, it is that we must be very careful with our predictions because they are often dead wrong.”

One potential scenario is that once children start returning to school on a consistent basis and become sick, the antibiotic prescribing rate will return to prepandemic levels. “Unfortunately, the previous decrease will have been just a little blip on the horizon for trends in overall antibiotic prescribing,” Mehrotra said.

Additionally, telemedicine visits versus in-person visits for the same condition can result in higher antibiotic prescribing, due to heightened physician uncertainty about whether the patient has a bacterial illness. “A better safe than sorry strategy kicks in,” Mehrotra said.

However, a second possibility, borne out by some of Mehrotra’s research, is a long-term reduction in antibiotic use because many children who become ill during the pandemic recover on their own, so going forward parents may think twice about making an office appointment.

1. Spigaglia P, Mastrantonio P, Barbanti F. Antibiotic resistances of Clostridium difficile. 

. 2018;1050:137-159. doi:10.1007/978-3-319-72799-8_9

2. Gerber JS, Jackson MA, Tamma PD, Zaoutis TE. Antibiotic stewardship in pediatrics. 

 2020;147(1):e2020040295. doi:10.1542/peds.2020-040295

3. Rastogi V, Pragya, Navneet Verma, et al. An overview on bacteriophages: a natural nanostructured antibacterial agent. 

. 2018;15(1):3-20. doi:10.2174/1567201813666160406115744

4. Brinkac L, Voorhies A, Gomez A, Nelson KE. The threat of antimicrobial resistance on the human microbiome. 

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5. Dhochak N, Singhal T, Kabra SK, Lodha R. Pathophysiology of COVID-19: Why children fare better than adults? 

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Articles

It is more important than ever for health care professionals to remember that overprescribing these drugs can have life-threatening consequences.

Pediatric update on antibiotic use

	Parents often carry misperceptions about the advantages and disadvantages of antibiotic use for pediatric acute respiratory infections, according to an Australian survey in the 

As a result, it is important that pediatricians convey honestly and frankly to parents the true benefits and harms of antibiotics, as most parents overestimate their value. Shared decision making is a good way of doing this.

	“Doctors need to be aware that most parents are coming in with massively optimistic expectations about the benefits of antibiotics,” says co-author Chris Del Mar, MD, a professor of public health and family physician at Bond University in Queensland, Australia. “The conversation needs to address that perception by providing accurate information.”

	In 2015, Del Mar and coauthor Tammy Hoffmann, PhD, a professor of Clinical Epidemiology at Bond University Centre for Research in Evidence-Based Practice, published in 

 a systematic review of patients’ expectations of the benefits and harms of treatments and tests for all indications.

“That study showed that across nearly every test and treatment studied, patients overestimate benefits and underestimate harm,” Hoffmann says.

	Through the years, the 2 authors have also researched antibiotics for acute respiratory infections, so after publication of their systematic review they knew there had not been any primary studies evaluating peoples’ expectations of antibiotic benefits.

	For the current study, the investigators interviewed 1 parent from 401 households across Australia (Table

	 “We were surprised by how much benefit parents thought antibiotics delivered for their child’s acute otitis media, acute cough, or sore throat. On average, parents believed that antibiotics would shorten the duration of illness by 3 to 3.5 days, when the reality is less than 0.5 days,” Del Mar says. “The perceived benefit was up to 5 to 10 times greater than reality.”

	Another surprise was what parents nominated as the minimally important clinical difference. “In other words, how much difference would be worthwhile taking antibiotics for,” Del Mar says. “Parents thought it was only worthwhile using antibiotics if they produced a shortening of illness duration of 3 to 3.5 days,” he says.

	This information can be useful to clinicians because it means that if clinicians were to explain to patients the quantified benefits of antibiotics for acute respiratory infections, “many patients may then likely think it not worthwhile taking and have less predilection for assuming an antibiotic is needed,” Del Mar says.

	Besides overestimating the benefits of antibiotics, most parents felt not sufficiently involved in decision making about whether their child needed antibiotics in the first place. “Parents wanted to be more involved,” Hoffmann says. “Most were not told how much benefit antibiotics provide or the potential harms from antibiotics. Parents expressed a desire for a collaborative discussion about whether their child actually needed antibiotics or not, and the pros and cons of using or not using them.”

	By empowering parents and clinicians to engage in shared decision making,

 “we anticipate that this can help to reduce antibiotic use for acute respiratory infections in primary care,” Hoffmann says.

	This belief is supported by a systematic review of all primary-care trials that evaluated interventions that facilitated shared decision making for acute respiratory infections, published in 2015 in the 

“This review shows that indeed shared decision making, if implemented, reduces the demand and the use of prescribed antibiotics,” says Del Mar, who along with Hoffmann was a co-author of the review.

	The review found that immediately after or within 6 weeks of consultation, 47% of patients in the control groups were given an antibiotic prescription, compared with 29% in the groups in which the doctors or patients had received the intervention to facilitate shared decision making (usually training or information).

	Another finding of the current study is that some parents mentioned resistance as a harm of antibiotics when asked about potential harms. “But a lot of people misunderstood what was meant by antibiotic resistance and interpreted it as their body becoming immune to the antibiotics,” Hoffmann says. “Therefore, physicians should explain to parents what antibiotic resistance is, and that every time you take antibiotics it increases the likelihood of resistance.”

	Del Mar adds that antibiotic resistance is not only a global threat to society, but a threat to the individual patient. “By taking antibiotics, resistance develops in the bacteria in the individual,” he says. “Then, if that individual becomes ill from a serious infection-mastoiditis, pneumonia meningitis, septicemia, and so on-this resistance can be transferred to a dangerous pathogen, which may mean it takes longer to find the right antibiotic, or maybe not at all for a tragic outcome.”

	A 2016 systematic review of 54 studies in the 

 assessed the public’s knowledge and beliefs about antibiotic resistance.

 The investigators found that 70% of participants had heard of antibiotic resistance, but that 88% believed it referred to changes in the human body. As for what causes resistance, 70% of respondents believed it was excessive antibiotic use and 62% thought it was not completing antibiotic courses.

	“I would be surprised if antibiotic resistance was routinely communicated during consultation by a community pediatrician in the United States,” Del Mar says. “But it is important that the physician talks about the benefits and the harms of using and not using antibiotics in consultation with parents. It should also be an explicit discussion, including how the parent feels about the amount of benefit their child may receive, as well as how the parent feels about the harms and the risks of them. Afterward, the physician and parent can make a decision together about moving forward.”

	Although shared decision making is desired by patients and may be an effective strategy for managing expectations and reducing unnecessary antibiotic prescriptions, “doctors need awareness of what shared decision making is," Hoffman says. "They often need skill training and support tools.”

	Moreover, “there is some indication that doctors also overestimate the benefits of antibiotics,” says Hoffmann, who along with Del Mar co-authored a systematic review published in March this year in 

 that shows that physicians tend to overestimate the benefits and underestimate the harms of medical care in general.

One of the included primary studies explored the expectations of antibiotics for acute respiratory infections held by European pediatricians.

	Del Mar says there are several factors fueling overinflated expectations of antibiotics. “Part of it is a human condition-that we are overoptimistic about lots of things, like not developing cancer or not getting into a motor accident or that our investments will return a good yield. It is a bias we all have,” he says.

	 “It is a complicated issue, ranging from doctors’ being ill-informed to being in denial, to being in the habit of using antibiotics routinely,” Del Mar says. “Hence, we have an inflationary mixture in the consultation: patients who grossly overestimate the benefits of antibiotics and clinicians who also overestimate their benefits, and probably neither thinking about their harms much.”

Drs. Hoffmann and Del Mar report no relevant financial disclosures

	1. Coxeter PD, Del Mar C, Hoffmann TC. Parents’ expectations and experiences of antibiotics for acute respiratory infections in primary care. 

	2. Hoffmann TC, Del Mar C. Patients' expectations of the benefits and harms of treatments, screening, and tests: a systematic review. 

	3. Hoffmann TC, Légaré F, Simmons MB, et al. Shared decision making: what do clinicians need to know and why should they bother? 

	4. Coxeter P, Del Mar CB, McGregor L, Beller EM, Hoffmann TC. Interventions to facilitate shared decision making to address antibiotic use for acute respiratory infections in primary care. 

	5. McCullough AR, Parekh S, Rathbone J, Del Mar CB, Hoffmann TC. A systematic review of the public’s knowledge and beliefs about antibiotic resistance. 

	6. Hoffmann TC, Del Mar C. Clinicians’ expectations of the benefits and harms of treatments, screening, and tests: a systematic review. 

Parents often carry misperceptions about the advantages and disadvantages of antibiotic use for pediatric acute respiratory infections, according to an Australian survey in the Annals of Family Medicine.

Parents overestimate benefits of antibiotics for acute respiratory infections

Children with asthma are 4 times more likely to have kidney stones than those without asthma, and vice versa, according to a study published online in the medical journal 

“We evaluated children with kidney stones and children with asthma,” says co-investigator Serpil Erzurum, MD, chair of the Lerner Research Institute at the Cleveland Clinic, Cleveland, Ohio. “In either case, asthma and kidney stones are associated with each other.”

Data for the retrospective study were gleaned from the Cleveland Clinic’s electronic medical records of pediatric patients aged between 6 months and 18 years with a diagnostic code of either asthma or kidney stone, from 2000 to 2014. A total of 865 patients had a diagnosis of nephrolithiasis and 36,518 patients had a diagnosis of asthma.

The prevalence of kidney stone alone was 0.08% compared with 6.79% for asthma alone. However, the prevalence of kidney stones in children with asthma was 6-fold higher. “To the best of our knowledge, this is the first time such a connection has been described. It is important that pediatricians have this knowledge base when caring for children,” says Manoj Monga, MD, director of the Stevan B. Streem Center for Endourology and Stone Disease in the Glickman Urological and Kidney Institute at the Cleveland Clinic and senior investigator of the study.

The Cleveland Clinic doctors were inspired to undertake the evaluation for a number of reasons, including the understanding that in children with cystic fibrosis, there is an increased incidence of kidney stones, for unclear reasons.

 “We thought that asthma, being an inflammatory airway disease, might be another population that could have similar findings,” Erzurum says. “The airways and the tubules of the kidney have surprisingly similar functions.”

Inflammation is a common underlying process in asthma and kidney stones.

 Nevertheless, the researchers were surprised to find a dramatic association between the 2 diseases. “By eventually understanding the reason for this co-occurrence, we will better understand asthma and kidney stones,” Erzurum says. “Hopefully, this will open up some basic biology that we can understand about both disorders, resulting in new ideas for studying these 2 diseases.”

The investigators did not find any meaningful differences in patient characteristics or demographics, including age, sex, and body mass index (BMI). However, socioeconomic factors were not evaluated. There also was no difference in inhaled beta agonists, inhaled corticosteroids, or any antiasthmatic medication use among asthma patients, with or without a stone diagnosis. On the other hand, asthma-stone patients were more than twice as likely to be on a combination inhaled corticosteroid plus long-acting beta agonist than asthma patients without a stone (29.7% vs. 13.7%, respectively).

“Because this was a historical study looking at our database, we are limited in what we can conclude,” says Erzurum, holder of the Alfred Lerner Memorial Chair in Innovative Biomedical Research at the Cleveland Clinic. “It could be that some of this association is related to drugs or medications being taken by these children. But we did not find any evidence for that when we tried to compare by controlling for the drugs they were using for their asthma.”

Asthma is a common diagnosis in children and kidney stones are also observed.

 “Both lead to discomfort,” Monga says. “Furthermore, parents miss work by staying home with their school-aged children.”

Based on the study, pediatricians should consider the co-occurrence of asthma and kidney stones.

Monga says it is too early for pediatricians to change their treatment protocols for treating asthma or kidney stones. Similarly, the results should not be overinterpreted. “If you are a child with asthma, you are likely to never have a kidney stone,” Monga says. “Kidney stones in childhood are still not that common. And if a child has kidney stones, there is nothing evidence based to consider this a process leading to asthma.”

Pediatricians are unlikely to be surprised by the study results, according to Erzurum. “In fact, long-time practicing pediatricians are likely to have seen asthma and kidney stones in their patients,” she says. “The study might be considered more of a confirmatory study of what pediatricians see in their daily practice.”

The Cleveland Clinic researchers are particularly proud of the study’s collaboration among various medical specialties, including urology and pulmonology. “Discovery occurs more rapidly by working together,” Erzurum says. The investigators hope to conduct a prospective follow-up trial.

“As a urologist, the fact that a significant proportion of the study’s pediatric population had both asthma and nephrolithiasis was of interest to me,” says Irene M. McAleer, MD, JD, MBA, a clinical professor of urology at the University of California, Irvine, and a pediatric urologist at Children’s Hospital of Orange County, Orange, California. “A pulmonary specialist may be more concerned that their patients with asthma may get kidney stones.”

McAleer says her own clinical experience of the connection between asthma and kidney stone has not been as remarkable as the study shows. “I tend to see more girls, particularly teenaged girls, more children with obesity, and more children with anatomic abnormalities that put them at risk for kidney or ureteral stones than noticing this association with asthma,” she says.

The study investigators’ speculation “that there may be some associated epithelial defect or condition that places this specific population at risk, like cystic fibrosis, is intriguing and sounds like a great idea for research for possible metabolic or molecular differences in these epithelial regions in these children, both for treatment and prevention of asthma and stone formation alike,” McAleer says.

Next: A paradigm shift in asthma treatment

McAleer found interesting the asthma treatment regimens. “Chronic steroid use, primarily oral administration, is associated with increase urolithiasis, due to increased mobilization of calcium from the bone and possible increased hypercalcuria,” she says. “It is uncertain that inhaled steroids would cause the same release of calcium.”

Additionally, the children that had 24-hour urine collections in the asthma and stone groups and stone-only group “did not have a markedly different urine calcium concentration, so it is difficult to see why these children at the Cleveland Clinic were more likely to have stones associated with their asthma,” McAleer says.

McAleer notes it is too early for pediatricians to be alarmed by any of the study’s findings. “I think that the association found here may be due to referral patterns to the Cleveland Clinic and their review of the data based on coding of the 2 conditions,” she says. “However, pediatricians should be aware that there may be a link between asthma and urolithiasis to help with a differential diagnosis for a child with abdominal or flank pain, with or without gross hematuria, as possibly having a kidney or ureteral stone, just as they are aware that children with cystic fibrosis are at higher risk for kidney or ureteral stone formation, due to their cystic fibrosis.”

Studying the cystic fibrosis population that has both significant pulmonary fibrosis and renal stone formation “may crack the presumed association that is softly associated in the general pediatric asthmatic population,” McAleer says.

Drs Erzurum, McAleer, and Monga report no relevant financial disclosures.

1. Kartha GK, Li I, Comhair S, Erzurum SC, Monga M. Co-occurrence of asthma and nephrolithiasis in children. 

2. Gibney EM, Goldfarb DS. The association of nephrolithiasis with cystic fibrosis. 

3. Khan SR. Reactive oxygen species, inflammation and calcium oxalate nephrolithiasis. 

4. Loftus PA, Wise SK. Epidemiology of asthma. 

5. Routh JC, Graham DA, Nelson CP. Epidemiological trends in pediatric urolithiasis at United States freestanding pediatric hospitals. 

Children with asthma are 4 times more likely to have kidney stones than those without asthma, and vice versa, according to a study published online in the medical journal PLoS One.

Bob Kronemyer

Articles

Pediatric update on antibiotic use

Parents overestimate benefits of antibiotics for acute respiratory infections

Asthma and kidney stones linked in children