Pneumococcal Vaccine Associated With Steep Decline in Antibiotic Use Among Young Children in Israel

Researchers compared trends in antibiotic prescription rates during the period preceding the pneumococcal conjugate vaccine (PCV), as well as the early and late PCV periods, among Jewish vs Bedouin children.

Antibiotic prescription rates were found to decline significantly among children younger than 5 years following implementation of the 7-valent/13-valent pneumococcal conjugate vaccine (PCV) in the Negev district in southern Israel, according to study results published in Clinical Infectious Diseases.

In this 13-year retrospective analysis from July 2005 through June 2018, researchers compared trends in antibiotic prescription rates per 1000 child-years during the pre-PCV period (July 2005-June 2009), early-PCV period (July 2010-June 2015), and late-PCV period (July 2015-June 2018) among Jewish vs Bedouin children, who have minimal social contact with one another. The researchers used an interrupted-time series analysis to evaluate antibiotic prescription rates adjusted for age, ethnicity, season, and antibiotic category, excluding parenteral antibiotics.

A total of 1,090,870 prescriptions were dispensed in the 13-year period, with 57% occurring in children younger than 2 years. Mean yearly prescription rates for all antibiotics per 1000 child-years during the pre-PCV period were 2590.3 for children younger than 2 years, 1393.4 for children aged between 2 and 4 years, and 1852.1 for children older than 5 years. Compared with Jewish children, overall rates were 1.6-fold higher among Bedouin children and peaked in the cold season.

Amoxicillin/amoxicillin-clavulanate was the most frequently prescribed antibiotic (75%), followed by azithromycin (14%) and oral second-generation cephalosporins (8%); proportions were similar between the 2 ethnic groups across all ages.

Following PCV implementation, antibiotic prescription rates for all antibiotics significantly declined and reached a plateau within 5 years, mainly driven by amoxicillin/amoxicillin-clavulanate, which is a first-line antibiotic for respiratory tract infections. Reduced rates of prescription of amoxicillin/amoxicillin-clavulanate were more pronounced during the cold season. The trend was statistically significant in Bedouin children younger than 2 years; however, by the late-PCV period, the rates were similar between the 2 groups.

Rates for azithromycin, which is used for many indications beyond respiratory tract infections, were not reduced. During the first 5 post-PCV years, an increasing trend in azithromycin use was seen among Bedouin and Jewish children; this trend reached significance in Jewish children younger than 2 years. It should be noted that this trend occurred only during the cold season, which the study investigators identify as a finding that warrants further research.

Conversely, rates for oral second-generation cephalosporins, which are often used for skin and soft tissue infections, were higher during the warm season. Given that rates of respiratory tract infection are lowest during the warm season, the researchers concluded that “PCVs might not have played a major role in [oral second-generation cephalosporin] reduction.”

The reduction in actual incidence rate ratio (aIRR), defined as mean late-PCV period vs pre-PCV period, for all dispensed antibiotic prescriptions was 344.7 (95% CI, 330.9-358.4), The reduction in relative-to-expected IRR (rIRR), defined as mean late-PCV period vs expected mean late-PCV period and extrapolated from pre-PCV trends, was 110.4 (95% CI, 96.9-123.7). For amoxicillin/amoxicillin-clavulanate, the reduction in aIRR was 300.2 and the reduction in rIRR was 142.3; for children younger than 2 years, the respective reductions were 653.2 and 387.2, respectively.

The investigators conclude that antibiotic prescription rates declined significantly in children younger than 5 years after PCV implementation in Israel with similar rates among Jewish and Bedouin children, driven mainly by amoxicillin/amoxicillin-clavulanate, supporting the causative role of PCV in preventing respiratory tract infections.

Disclosure: Several study authors declared affiliations with the pharmaceutical industry. Please see the original reference for a full list of authors’ disclosures.


Danino D, Van Der Beek BA, Givon-Lavi N, Greenberg D, Ben-Shimol S, Dagan R. Unravelling the impact of pneumococcal conjugate vaccines on ambulatory antibiotic drug consumption in young children: an interrupted time series analysis. Clin Infect Dis. Published online May 20, 2021. doi:10.1093/cid/ciab413