The Burden and Impact of Antibiotic Prescribing in Ambulatory Pediatrics

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Antibiotics are one of the most commonly prescribed classes of medication for children and adolescents. While they are arguably the most powerful tool we possess against bacterial infections, they are frequently given to children whose illnesses are due to viruses or other non-infectious etiologies. When antibiotics are not used judiciously, the consequences can be serious and accumulate over time. This review article quantifies the burden of antimicrobial use in the pediatric outpatient setting in the United States, reviews recommended first line antibiotic regimens for common outpatient pediatric and adolescent conditions, investigates the reasons for inappropriate prescribing of antibiotics in outpatient healthcare settings, and explores the range of consequences of overuse and inappropriate use of antibiotics, from adverse drug reactions to impact on the microbiome to rising rates of antimicrobial resistance in common ambulatory conditions.

Introduction

Concern for infection is one of the top three reasons that children and adolescents are seen by a physician in clinic, accounting for 37 million, or about 20%, of all clinic visits.1 Young children have higher rates of antibiotic prescription than any other cohort of the population.2 The discovery of antibiotics was one of the most impactful medical advances for the health of children and dramatically reduced morbidity and mortality due to infectious diseases in the past century. However, rising trends in antibiotic use in both inpatient and outpatient clinical settings coupled with the emergence of antimicrobial resistance threaten the effectiveness of these life-saving drugs. Use of medically important antimicrobials in livestock and veterinary practices has also grown tremendously over the past several decades, adding significantly to the total global antimicrobial burden.3 The purpose of this review is to explore the current patterns of antibiotic use in pediatric ambulatory settings, review the recommended first-line antibiotics for common outpatient pediatric conditions and discuss the individual and societal consequences of increased, and at times inappropriate, antibiotic use.

Section snippets

Antibiotic prescribing patterns in the US pediatric population

About one-quarter of all pediatric ambulatory visits result in an antibiotic prescription; the approximately 70 million antibiotic prescriptions written annually represent one-quarter of all medications dispensed to children.46 Fig. 1 illustrates the distribution of ambulatory diagnoses leading to antibiotic prescription in children in 2010-2011, with otitis media, pharyngitis and sinusitis accounting for nearly half of all antibiotic associated diagnoses. In a recent retrospective study by

Geographic and specialty variability

Antibiotic prescribing varies by geographic region and clinician subspecialty. On a global scale, studies of retail pharmaceutical sales data comparing antibiotic prescription rates from different industrialized countries determined that the United States was in the top quartile of prescribing nations, prescribing nearly 25 doses of antibiotics per 1000 inhabitants per day. This is more than double the antibiotic prescribing rate in Germany or The Netherlands, as demonstrated in Fig. 2.8 Within

Appropriateness of antibiotic prescribing

Among the large volume of antibiotics prescribed to children every year, a substantial proportion of these antibiotics are considered inappropriate. Many childhood infections can be attributed to viruses, including bronchiolitis, bronchitis, upper respiratory infections (URIs) and many cases of pharyngitis and non-suppurative otitis media. In a 2014 meta-analysis, acute respiratory tract infections, which included otitis media, sinusitis, bronchitis, URIs and pharyngitis, were estimated to

Common acute ambulatory pediatric conditions and antibiotic use

Acute otitis media: Recently updated AAP guidelines address when antibiotics should be prescribed for AOM and which antibiotics should be used.13 Nevertheless, prescribing practices vary by geographic region and from physician to physician. Not all children with AOM require antibiotic treatment. A 2015 Cochrane review found that

60% of children with AOM recovered within 24 h, with or without antibiotics.

The same review noted that a significantly higher proportion of children who

Treatment of patients with penicillin allergy

Penicillin allergy is reported in 5–10% of children; however it is estimated that less than one percent of the population has a true IgE-mediated allergy, such as urticaria, angioedema or anaphylaxis.48, 49 This difference in reported penicillin allergy and true penicillin allergy is important because patients with reported penicillin allergy have worse clinical outcomes and increased health care costs compared to patients without reported penicillin allergy. A penicillin or

Adverse effects of antibiotic use

The consequences of inappropriate antibiotic use extend from direct and immediate effects on the individual using these medications to treat a current infection, to potential for developing chronic illness, to worldwide spread of multi-drug resistant bacteria.

Individual effects

All medications, even the most benign, have consequences. Adverse drug reactions include immediate (IgE mediated) allergic reaction, delayed (non-IgE mediated) reactions, drug toxicity, intolerance and idiosyncratic reactions.58 The most common manifestations of adverse drugs reactions observed in children are gastrointestinal or dermatologic in nature.59 Antibiotic-associated diarrhea occurs in up to 25% of patients exposed to antibiotics, depending on the antibiotic.60 Diarrhea occurs in 25%

Societal effects of antibiotic overuse

Beyond the significant individual consequences of antibiotic overuse, there are mounting negative consequences to society, primarily in the form of antimicrobial resistance (AMR). Mechanisms of resistance to antimicrobial agents have been known since the discovery of the first antibiotic. The first clinically effective antibiotics, the sulfonamides, were introduced in 1937 and within a few years, sulfonamide resistant bacterial strains were discovered. Penicillinase producing bacteria were

Current trends in antimicrobial resistance

Recent estimates of the burden of antimicrobial resistance suggest that there are approximately 700,000 deaths worldwide every year due to infection with antimicrobial resistant bacteria, with nearly 50,000 of these deaths occurring in the United States and Europe.86 A report led by economist Jim O'Neil on antimicrobial resistance commissioned by the British government in 2014 projected that the number of annual deaths attributable to antimicrobial resistance would surpass 10 million by the

Antimicrobial resistance threats in the pediatric ambulatory setting

The most critical antimicrobial resistance threats worldwide according the World Health Organization are drug resistant malaria, multidrug resistant (MDR) and extensively drug resistant (XDR) tuberculosis and resistant HIV. These conditions, while increasing in prevalence and threatening significant morbidity and mortality in developing countries, are not commonly encountered in the United States in pediatric ambulatory primary care settings. The section below outlines the epidemiology and

Resistant Streptococcus pneumoniae and respiratory infections

Streptococcus pneumoniae, or pneumococcus, commonly colonizes the nasopharynx in children and is a frequent cause of infections such as acute otitis media, sinusitis, community-acquired pneumonia and meningitis. S. pneumoniae has traditionally been considered highly susceptible to penicillin, however over the past several decades resistance to one or several antibiotic classes has steadily been rising. Drug resistant Streptococcus pneumoniae is considered a serious threat, with an estimated

MRSA and skin and soft tissue infections

The CDC estimates that one in three people have nasal colonization with Staphylococcus aureus and that two out of every one hundred people carry MRSA.96 While initially considered a hospital acquired pathogen, community acquisition of MRSA now accounts for the majority of all invasive MRSA infections in children.96 In the ambulatory setting, community acquired MRSA commonly causes purulent skin and soft tissue infections (SSTIs). MRSA SSTIs are associated with higher rates of mortality, longer

Extended-spectrum beta-lactamase producing Enterobacteriaceae and UTIs

Many bacteria have the ability to produce beta-lactamase enzymes, which counteract beta-lactam antibiotics such as penicillin or cephalosporins. Some bacteria are inherently able to produce beta-lactamases but others gain the ability to produce these enzymes by plasmids transferred from bacteria to bacteria. There are several different types of beta lactamase enzymes, including some with a broad range of affected targets. Bacteria possessing these broad-range enzymes are known as

Multi drug-resistant gonorrhea

Multi-drug resistant Neisseria gonorrhoeae, the bacteria that causes the sexually transmitted infection gonorrhea, is considered one of the three “urgent threats” in antimicrobial resistance by the CDC.92 The WHO estimates that 78 million people are infected with gonorrhea worldwide every year with almost 500,000 cases reported in the United States annually. The rates of gonorrhea are rising fastest in the adolescent and young adult population.104, 105 One quarter of these new cases are

Conclusion

Antibiotic use in children has doubled over the past several decades and approximately one quarter of these antibiotics are unnecessary. Unintended consequences of antibiotic use include short term and long term effects on individual patients, as well as harmful societal effects by selecting for antibiotic-resistant bacterial strains. Antimicrobial resistance continues to rise, threatening the effectiveness of available antibiotics. While the projected global impact on morbidity, mortality, and

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