As vaccine coverage climbed among young children, antibiotic use plummeted, showing how immunizations may be quietly reshaping the battle against drug resistance.
Study: Temporal trends in vaccination and antibiotic use among young children in the United States, 2000–2019. Image credit: adriaticfoto/Shutterstock.com
Antibiotic use should decline with widespread and appropriately administered vaccination programs, but the evidence is lacking. A recent paper published in Antimicrobial Stewardship and Healthcare Epidemiology examines this impact among young American children over 20 years, 2000-2019.
Introduction
Antibiotic use is common and often medically inappropriate, promoting the emergence and rise of antimicrobial resistance (AMR). This poses an unprecedented public health challenge, threatening to take the world back to pre-antibiotic-era days.
Intensive efforts were made to promote proper antibiotic use during the study period. Clinical guidelines were issued for managing middle ear infections, sinusitis, pneumonia, and throat infections, such as when to prescribe antibiotics, which antibiotics to use in different situations, and the role of watchful waiting.
Multiple measures were launched to tackle AMR, including the Core Elements of Hospital Antibiotic Stewardship Programs and the National Action Plan for Combating Antibiotic-Resistance Bacteria, from the Centers for Disease Prevention and Control (CDC).
Immunization programs prevent several common infectious diseases in children, for which antibiotics are commonly prescribed. Reasons for such use include the difficulty distinguishing bacterial from viral respiratory infections in young children, and precautionary use to prevent rapid and dangerous clinical deterioration in this vulnerable population.
Earlier studies suggest that pneumococcal and influenza vaccines reduce antibiotic use in children. Yet, they have focused primarily on individual vaccines, ignoring the synergistic benefits of immunization programs targeting multiple disease-causing microbes.
The current study sought to fill this gap, using 20 years’ worth of claims data, to assess the real-world impact of vaccination on antibiotic use in under-fives. However, the authors note that the ecological study design does not allow for conclusions about causality.
About the study
The study used the Merative® MarketScan Commercial Claims and Encounters database to collect data on the uptake of four common childhood vaccines: pneumococcal conjugate, Haemophilus influenzae type b, diphtheria-tetanus-pertussis, and influenza vaccines. The data also covered antibiotic prescriptions and antibiotic-treated respiratory tract infections among children under five during the study period.
Depending on annual vaccination evaluations, children were categorized as having received all four, 1 to 3, or no vaccines.
Study results
Vaccination trends
The study showed that 32.5% of 6.7 million under-five children received all four vaccines in 2004. This increased to 67% in 2019, with only 2.5% being unvaccinated.
Antibiotic use
Broad-spectrum antibiotics comprised about half of the antibiotic prescriptions over most of the study period. Penicillins made up 50% to 61%, vs. cephalosporins and macrolides, which comprised 30% to 45%.
Overall, antibiotic prescriptions fell by half over this period, from 1.9 to 1.0 per person-year. The largest reductions were during 2003-2007 and 2010-2013.
The most affected were macrolide antibiotics, which were reduced by 73%, followed by broad-spectrum antibiotics, which decreased by 57%, and penicillins, which declined by 44%.
These findings are consistent with previous studies showing, for instance, a 6% reduction in antibiotic prescriptions after flu vaccine uptake increased 10%. Macrolides showed the largest decrease, being the most frequently prescribed for respiratory infections, especially when the patient is allergic to penicillin.
Respiratory infections
The most common antibiotic-treated respiratory infection was otitis media. Viral respiratory infections made up 30% to 38 %, and throat infections 11% to15%.
During the study period, antibiotic-treated respiratory infections decreased by more than a third from 2.4 to 1.6 episodes per person-year between 2019 and 2000. Sinusitis decreased by 65% and throat infections by 40%.
There was a proportional decrease in all antibiotic-treated respiratory infections, indicating the generalized impact of vaccination. Prior research confirms pneumococcal vaccines reduce children's risk of acute middle ear infections and antibiotic usage. Influenza vaccines decrease the rate of acute respiratory infections, prompt precautionary antibiotic use, and predispose patients to secondary bacterial infections.
Stable urinary infection rates
Antibiotic-treated urinary tract infection (UTI) rates remained relatively stable throughout the study period, except for a modest decrease of 5% to 24% observed during 2016 and 2019.
Implications
The slow decline in antibiotic usage from 2000 onwards coincided with the increase in vaccine uptake until 2011. The most significant drop in antibiotic use for viral infections occurred after integrating the flu vaccine into the routine childhood immunization schedule in 2004. This emphasizes the contribution of prophylactic antibiotics for influenza, the most common viral respiratory infection.
After this point, the decline was mainly due to antibiotic stewardship programs, since vaccination rates remained stable until 2017. The slight increase in vaccine uptake and continuing antibiotic stewardship were associated with a steeper drop in antibiotic use. The primary vaccine impact may have been on bacterial respiratory infections, which might explain the relatively smaller decline in antibiotic use for urinary infections.
Thus, increased vaccine uptake and antibiotic stewardship efforts contributed jointly to this trend. Other contributors include better diagnostic testing, more managed healthcare availability for children, and higher socioeconomic status, which affects healthcare access, infection risk, and efforts to get healthcare.
Additionally, AMR influences antibiotic selection. High macrolide resistance caused many physicians to prescribe other drugs. Also, increasing breastfeeding in the USA during the study period protects against acute ear infections and other common infections.
Rising electronic health record use might also have helped track past medical history and antibiotic prescription practices and provided automated help accessing best practices.
Conclusions
These findings suggest a steep decline in antibiotic use among young children in the USA, coinciding with increased childhood vaccine uptake. Thus, immunization programs significantly affect public health beyond vaccine-preventable diseases.
However, the authors caution that the study cannot prove that vaccination alone caused the reduction in antibiotic use. Future studies should include Medicaid and uninsured children, who are less likely to be vaccinated, and explore the effects of different vaccine combinations.
“These findings highlight the potential policy implications of integrating vaccination programs into antimicrobial stewardship efforts to help reduce unnecessary antibiotic use, ultimately supporting public health efforts to combat antibiotic resistance,” the study concludes.
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